Cabozantinib or Paclitaxel in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer

Phase 2

Completed

• Conditions: Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
• Interventions: Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel

• Registration Number: NCT01716715
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This randomized phase II trial studies how well giving cabozantinib-s-malate or paclitaxel works in treating patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cavity cancer. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether cabozantinib-s-malate or paclitaxel is more effective at treating patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cavity cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the activity of cabozantinib (cabozantinib-s-malate) relative to weekly paclitaxel in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer with a log-rank test assessing progression-free survival (PFS) at 3.68 months (approximately pre-cycle 5) and 7.36 months (approximately pre-cycle 9).

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE).

II. To estimate and compare the proportion of patients responding to therapy by Response Evaluation Criteria for Solid Tumors (RECIST), cancer antigen 125 (CA125) response, the overall survival (OS), and the duration of response in each arm.

TERTIARY OBJECTIVES:

I. To retrospectively correlate c-met proto-oncogene (MET) expression with overall outcome.

II. To retrospectively correlate c-MET copy number with overall outcome.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cabozantinib-s-malate orally (PO) once daily (QD) on days 1-28.

ARM II: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-10-23
• Study First Submitted QC: 2012-10-25
• Study First Posted: 2012-10-30
• Study Start: 2012-11-06
• Primary Completion: 2015-03-16
• Study Completion: 2019-02-09
• Results First Submitted: 2019-06-26
• Status Verified: 2020-02
• Results First Submitted QC: 2020-02-28
• Last Update Submitted: 2020-02-28
• Results First Posted: 2020-03-10
• Last Update Posted: 2020-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 111

Inclusion Criteria

• Patients must have recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma; histologic documentation of the original primary tumor is required via the pathology report

• Patients must have measurable disease or non-measurable (detectable) disease:

  • Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be greater than or equal to 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray; lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI

  • Non-measurable (detectable) disease is defined in this protocol as the absence of measurable disease but at least one of the following conditions:

    • Ascites and/or pleural effusion attributed to tumor
    • Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions

• Patients with measurable disease must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

• Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase III or rare tumor protocol for the same patient population; in addition, patients must not be eligible for the currently active phase II cytotoxic protocol in platinum resistant disease

• Patients must have a GOG performance status of 0, 1, or 2

• Recovery from effects of recent surgery, radiotherapy, or chemotherapy to baseline or CTCAE =< grade 1 toxicity from all prior therapies except alopecia and other non-clinically significant adverse events (AE's):

  • Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
  • Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to treatment
  • Any other prior therapy directed at the malignant tumor, including chemotherapy, biological/targeted (non-cytotoxic) agents and immunologic agents, must be discontinued at least three weeks prior to treatment
  • Chimeric or human or humanized monoclonal antibodies (including bevacizumab) or vascular endothelial growth factor (VEGF) receptor fusion proteins (including VEGF TRAP/aflibercept) must be discontinued for at least 12 weeks prior to treatment
  • Investigational agents must be discontinued for at least 28 days prior to treatment
  • Any prior radiation therapy must be discontinued at least four weeks prior to treatment

• Prior therapy

  • Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab) or extended therapy administered after surgical or non-surgical assessment; if patients were treated with paclitaxel for their primary disease, this could have been given weekly or every 3 weeks
  • Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease, with no more than 1 non-platinum, non-taxane regimen; treatment with weekly paclitaxel for recurrent or persistent disease is NOT allowed
  • Patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy as part of their primary treatment regimen
  • Patients must have NOT received any biologic/targeted (non-cytotoxic) therapy targeting the VEGF and/or MET pathways for management of recurrent or persistent disease
  • For the purposes of this study, poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors will be considered "cytotoxic"; patients are allowed to receive, but are not required to receive, PARP inhibitors for management of primary or recurrent/persistent disease (either alone or in combination with cytotoxic chemotherapy); PARP inhibitors will NOT count as a prior regimen when given alone

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

• Platelets greater than or equal to 100,000/mcl

• Hemoglobin greater than or equal to 9 g/dL

• Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.3 x institutional upper limit of normal (ULN)

• Partial thromboplastin time (PTT) less than or equal to 1.3 x ULN

• Creatinine less than or equal to 1.5 x ULN

• Phosphorus, corrected calcium, magnesium and potassium greater than or equal to institutional lower limit of normal (LLN)

• Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended

• Bilirubin less than or equal to 1.5 x ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN

• Alkaline phosphatase less than or equal to 2.5 x ULN

• Albumin greater than or equal to 2.8 g/dL

• Lipase less than or equal to 2 x ULN

• No radiologic or clinical evidence of pancreatitis

• Patients must have a normal baseline thyroid stimulating hormone (TSH); a history of hypothyroidism and/or hyperthyroidism is allowed

• Neuropathy (sensory and motor) less than or equal to grade 1

• Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception; sexually active subjects must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug, even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug; pregnant women are excluded from this study

• Patients must have signed an approved informed consent and authorization permitting the release of personal health information

• Patients must meet pre-entry requirements

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Exclusion Criteria

• Patients who have had previous treatment with cabozantinib; patients who have received previous treatment with weekly paclitaxel for recurrent or persistent disease

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis or thoracic cavity within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Uncontrolled hypertension, defined as systolic greater than 140 mm Hg or diastolic greater than 90 mm Hg despite antihypertensive medications

• Myocardial infarction or unstable angina within 6 months prior to registration

• New York Heart Association (NYHA) class II or greater congestive heart failure

• History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication; this does not include asymptomatic atrial fibrillation with controlled ventricular rate

• Any history of congenital long QT syndrome

• The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; note: if initial QTcF is found to be > 500 ms, two additional electrocardiogram (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard

• Patients with serious non-healing wound, ulcer, or bone fracture within 28 days before treatment

• Patients with history of organ transplant

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving (in contact with, invading or encasing) major vessels

• Patients who have experienced any of the following:

  • Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
  • Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment
  • Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment

• Patients who have radiographic evidence of cavitating pulmonary lesion(s)

• Patients who have tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before treatment

• Gastrointestinal disorders, particularly those with potential risk of perforation or fistula formation including:

  • Any of the following within 28 days of registration

    • Intra-abdominal tumor/metastases invading GI mucosa
    • Active peptic ulcer disease
    • Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
    • Malabsorption syndrome

  • Any of the following within 6 months of registration

    • Abdominal fistula
    • Gastrointestinal perforation
    • Bowel obstruction or gastric outlet obstruction; note: patients requiring drainage gastrostomy (e.g., percutaneous endoscopic gastrostomy [PEG] tube) and/or parenteral hydration and/or nutrition are not eligible
    • Intra-abdominal abscess; note: complete resolution of an intra-abdominal abscess must be confirmed prior to registration even if the abscess occurred more than 6 months prior to registration

• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures which are not controlled with non-enzyme inducing anticonvulsants, any brain metastases and/or epidural disease, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months prior to the first date of study treatment

• The subject requires chronic concomitant treatment of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort)

• Patients who are unable or unwilling to swallow tablets

• Patients who are pregnant or nursing

• The subject requires concomitant treatment, in therapeutic doses, with anti-coagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor Xa inhibitors or antiplatelet agents (i.e. clopidogrel); low dose aspirin (=< 81 mg/day) low-dose warfarin (=< 1 mg/day) and prophylactic low molecular weight heparin are permitted

• Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications

• Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications

• Patients with concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (cabozantinib-s-malate)	Cabozantinib S-malate	Patients receive cabozantinib-s-malate PO QD on days 1-28.
Arm I (cabozantinib-s-malate)	Laboratory Biomarker Analysis	Patients receive cabozantinib-s-malate PO QD on days 1-28.
Arm II (paclitaxel)	Laboratory Biomarker Analysis	Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.
Arm II (paclitaxel)	Paclitaxel	Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.

Primary Outcome Measures

Name	Time	Method
Event Free Survival	The duration of time from study entry to time to progression or death,or begining a subsequent therapy, whichever occurs first, assessed up to 32 weeks	Time from patient entry until progression, death, or beginning a subsequent therapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.",

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Grade 3 or Higher Adverse Events by Type	Up to 30 days after completion of study treatment	Toxicities will be characterized by their frequency and severity, grade 3 and above.
Response, Assessed According to RECIST Version 1.1	CT or MRI used to follow lesion every 8 weeks for the first 8 months, then every 12 weeks until disease progression, approximately 2.5 years	Complete and Partial Tumor Response by RECIST. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Percentage of Participants With CA125 Response.	Prior to each cycle of treatment. Then follow-up every 3 months for 2 years then then every 6 months, up to 2.5 years.	Complete and Partial Tumor Response by CA125. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.",
Overall Survival	The duration of time from study entry to time of death or the date of last contact, an average of 2.5 years.	The time from randomization until death or date of last contact. Endpoint is death. Patients who are not observed with an endpoint are censored.
To Estimate the Response Duration Among Patients Who Respond.	From the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented or date of death from any cause, whichever came first, assessed up to 18 months.	The time participant is in response.Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.",

Trial Locations

Locations (173)

Los Angeles County-USC Medical Center; 🇺🇸 Los Angeles, California, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Cleveland Clinic Cancer Center/Fairview Hospital; 🇺🇸 Cleveland, Ohio, United States

Riverside Methodist Hospital; 🇺🇸 Columbus, Ohio, United States

Grant Medical Center; 🇺🇸 Columbus, Ohio, United States

Mount Carmel Health Center West; 🇺🇸 Columbus, Ohio, United States

Doctors Hospital; 🇺🇸 Columbus, Ohio, United States

Women's Cancer Center of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Indiana University/Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Lyndon Baines Johnson General Hospital; 🇺🇸 Houston, Texas, United States

Swedish Medical Center-First Hill; 🇺🇸 Seattle, Washington, United States

Pacific Gynecology Specialists; 🇺🇸 Seattle, Washington, United States

John Muir Medical Center-Concord Campus; 🇺🇸 Concord, California, United States

Mayo Clinic in Florida; 🇺🇸 Jacksonville, Florida, United States

Good Samaritan Regional Health Center; 🇺🇸 Mount Vernon, Illinois, United States

McFarland Clinic PC-Boone; 🇺🇸 Boone, Iowa, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center; 🇺🇸 Burbank, California, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Gynecologic Oncology Associates-Newport Beach; 🇺🇸 Newport Beach, California, United States

University of South Alabama Mitchell Cancer Institute; 🇺🇸 Mobile, Alabama, United States

University of Chicago Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Mercy Medical Center-West Lakes; 🇺🇸 West Des Moines, Iowa, United States

Cancer Center of Kansas - Fort Scott; 🇺🇸 Fort Scott, Kansas, United States

Cancer Center of Kansas-Wichita Medical Arts Tower; 🇺🇸 Wichita, Kansas, United States

Cooper Hospital University Medical Center; 🇺🇸 Camden, New Jersey, United States

UNC Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

Bronson Methodist Hospital; 🇺🇸 Kalamazoo, Michigan, United States

New Hanover Regional Medical Center/Zimmer Cancer Center; 🇺🇸 Wilmington, North Carolina, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

Saint Francis Medical Center; 🇺🇸 Cape Girardeau, Missouri, United States

Sanford Clinic North-Fargo; 🇺🇸 Fargo, North Dakota, United States

CoxHealth South Hospital; 🇺🇸 Springfield, Missouri, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Baystate Medical Center; 🇺🇸 Springfield, Massachusetts, United States

Sanford Joe Lueken Cancer Center; 🇺🇸 Bemidji, Minnesota, United States

University of Massachusetts Memorial Health Care; 🇺🇸 Worcester, Massachusetts, United States

West Michigan Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

Carolinas Medical Center/Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Dartmouth Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States

Mercy Hospital Saint Louis; 🇺🇸 Saint Louis, Missouri, United States

Saint Dominic-Jackson Memorial Hospital; 🇺🇸 Jackson, Mississippi, United States

Sanford Bismarck Medical Center; 🇺🇸 Bismarck, North Dakota, United States

Stony Brook University Medical Center; 🇺🇸 Stony Brook, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone; 🇺🇸 New York, New York, United States

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

Columbus Oncology and Hematology Associates Inc; 🇺🇸 Columbus, Ohio, United States

Summa Akron City Hospital/Cooper Cancer Center; 🇺🇸 Akron, Ohio, United States

Miami Valley Hospital; 🇺🇸 Dayton, Ohio, United States

The Don and Sybil Harrington Cancer Center; 🇺🇸 Amarillo, Texas, United States

Virginia Commonwealth University/Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States

Knox Community Hospital; 🇺🇸 Mount Vernon, Ohio, United States

Strecker Cancer Center-Belpre; 🇺🇸 Belpre, Ohio, United States

Adena Regional Medical Center; 🇺🇸 Chillicothe, Ohio, United States

Delaware Health Center-Grady Cancer Center; 🇺🇸 Delaware, Ohio, United States

Delaware Radiation Oncology; 🇺🇸 Delaware, Ohio, United States

Lancaster Radiation Oncology; 🇺🇸 Lancaster, Ohio, United States

Hillcrest Hospital Cancer Center; 🇺🇸 Mayfield Heights, Ohio, United States

Newark Radiation Oncology; 🇺🇸 Newark, Ohio, United States

Columbus NCI Community Oncology Research Program; 🇺🇸 Columbus, Ohio, United States

Marietta Memorial Hospital; 🇺🇸 Marietta, Ohio, United States

Fairfield Medical Center; 🇺🇸 Lancaster, Ohio, United States

Springfield Regional Medical Center; 🇺🇸 Springfield, Ohio, United States

Northwest Hospital; 🇺🇸 Seattle, Washington, United States

Wenatchee Valley Hospital and Clinics; 🇺🇸 Wenatchee, Washington, United States

MultiCare Tacoma General Hospital; 🇺🇸 Tacoma, Washington, United States

Genesis Healthcare System Cancer Care Center; 🇺🇸 Zanesville, Ohio, United States

Sanford Cancer Center Oncology Clinic; 🇺🇸 Sioux Falls, South Dakota, United States

Baylor All Saints Medical Center at Fort Worth; 🇺🇸 Fort Worth, Texas, United States

University of Virginia Cancer Center; 🇺🇸 Charlottesville, Virginia, United States

PeaceHealth Medical Group PC; 🇺🇸 Bellingham, Washington, United States

Marshfield Clinic Cancer Center at Sacred Heart; 🇺🇸 Eau Claire, Wisconsin, United States

Marshfield Medical Center; 🇺🇸 Marshfield, Wisconsin, United States

Harrison Medical Center; 🇺🇸 Bremerton, Washington, United States

Providence Regional Cancer Partnership; 🇺🇸 Everett, Washington, United States

ProHealth Oconomowoc Memorial Hospital; 🇺🇸 Oconomowoc, Wisconsin, United States

Olympic Medical Cancer Care Center; 🇺🇸 Sequim, Washington, United States

Saint Joseph Medical Center; 🇺🇸 Tacoma, Washington, United States

Skagit Valley Hospital Regional Cancer Care Center; 🇺🇸 Mount Vernon, Washington, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Providence Saint Mary Regional Cancer Center; 🇺🇸 Walla Walla, Washington, United States

Marshfield Medical Center-Marshfield; 🇺🇸 Marshfield, Wisconsin, United States

University of Wisconsin Hospital and Clinics; 🇺🇸 Madison, Wisconsin, United States

Saint Michael's Hospital; 🇺🇸 Stevens Point, Wisconsin, United States

ProHealth Waukesha Memorial Hospital; 🇺🇸 Waukesha, Wisconsin, United States

Marshfield Medical Center-Rice Lake; 🇺🇸 Rice Lake, Wisconsin, United States

Ascension Saint Mary's Hospital; 🇺🇸 Rhinelander, Wisconsin, United States

Marshfield Clinic - Weston Center; 🇺🇸 Weston, Wisconsin, United States

Marshfield Clinic - Wisconsin Rapids Center; 🇺🇸 Wisconsin Rapids, Wisconsin, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Mercy Hospital Springfield; 🇺🇸 Springfield, Missouri, United States

Kaiser Permanente Washington; 🇺🇸 Seattle, Washington, United States

University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Nebraska Methodist Hospital; 🇺🇸 Omaha, Nebraska, United States

Mary Greeley Medical Center; 🇺🇸 Ames, Iowa, United States

Medical Oncology and Hematology Associates-Des Moines; 🇺🇸 Des Moines, Iowa, United States

Saint Ann's Hospital; 🇺🇸 Westerville, Ohio, United States

USC / Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

The Hospital of Central Connecticut; 🇺🇸 New Britain, Connecticut, United States

Beebe Medical Center; 🇺🇸 Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States

Northeast Georgia Medical Center-Gainesville; 🇺🇸 Gainesville, Georgia, United States

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler; 🇺🇸 Savannah, Georgia, United States

University of Hawaii Cancer Center; 🇺🇸 Honolulu, Hawaii, United States

Sudarshan K Sharma MD Limited-Gynecologic Oncology; 🇺🇸 Hinsdale, Illinois, United States

Decatur Memorial Hospital; 🇺🇸 Decatur, Illinois, United States

Saint Vincent Hospital and Health Care Center; 🇺🇸 Indianapolis, Indiana, United States

McFarland Clinic PC - Ames; 🇺🇸 Ames, Iowa, United States

Mercy Cancer Center-West Lakes; 🇺🇸 Clive, Iowa, United States

Iowa Methodist Medical Center; 🇺🇸 Des Moines, Iowa, United States

Medical Oncology and Hematology Associates-Laurel; 🇺🇸 Des Moines, Iowa, United States

Iowa-Wide Oncology Research Coalition NCORP; 🇺🇸 Des Moines, Iowa, United States

Mercy Medical Center - Des Moines; 🇺🇸 Des Moines, Iowa, United States

Iowa Lutheran Hospital; 🇺🇸 Des Moines, Iowa, United States

Cancer Center of Kansas - Dodge City; 🇺🇸 Dodge City, Kansas, United States

University of Iowa/Holden Comprehensive Cancer Center; 🇺🇸 Iowa City, Iowa, United States

Cancer Center of Kansas - Chanute; 🇺🇸 Chanute, Kansas, United States

McFarland Clinic PC-Marshalltown; 🇺🇸 Marshalltown, Iowa, United States

Cancer Center of Kansas - El Dorado; 🇺🇸 El Dorado, Kansas, United States

Cancer Center of Kansas-Kingman; 🇺🇸 Kingman, Kansas, United States

Cancer Center of Kansas-Independence; 🇺🇸 Independence, Kansas, United States

Cancer Center of Kansas - Newton; 🇺🇸 Newton, Kansas, United States

Cancer Center of Kansas-Liberal; 🇺🇸 Liberal, Kansas, United States

Cancer Center of Kansas - McPherson; 🇺🇸 McPherson, Kansas, United States

Cancer Center of Kansas-Manhattan; 🇺🇸 Manhattan, Kansas, United States

Cancer Center of Kansas - Pratt; 🇺🇸 Pratt, Kansas, United States

Cancer Center of Kansas - Parsons; 🇺🇸 Parsons, Kansas, United States

Cancer Center of Kansas - Salina; 🇺🇸 Salina, Kansas, United States

Cancer Center of Kansas - Wellington; 🇺🇸 Wellington, Kansas, United States

Associates In Womens Health; 🇺🇸 Wichita, Kansas, United States

Cancer Center of Kansas - Wichita; 🇺🇸 Wichita, Kansas, United States

Wichita NCI Community Oncology Research Program; 🇺🇸 Wichita, Kansas, United States

Via Christi Regional Medical Center; 🇺🇸 Wichita, Kansas, United States

Maine Medical Center-Bramhall Campus; 🇺🇸 Portland, Maine, United States

Cancer Center of Kansas - Winfield; 🇺🇸 Winfield, Kansas, United States

Maine Medical Center- Scarborough Campus; 🇺🇸 Scarborough, Maine, United States

Union Hospital of Cecil County; 🇺🇸 Elkton, Maryland, United States

Massachusetts General Hospital Cancer Center; 🇺🇸 Boston, Massachusetts, United States

Borgess Medical Center; 🇺🇸 Kalamazoo, Michigan, United States

NYU Winthrop Hospital; 🇺🇸 Mineola, New York, United States

Cancer Research for the Ozarks NCORP; 🇺🇸 Springfield, Missouri, United States

Sanford Roger Maris Cancer Center; 🇺🇸 Fargo, North Dakota, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

The Mark H Zangmeister Center; 🇺🇸 Columbus, Ohio, United States

Grady Memorial Hospital; 🇺🇸 Delaware, Ohio, United States

Licking Memorial Hospital; 🇺🇸 Newark, Ohio, United States

Women and Infants Hospital; 🇺🇸 Providence, Rhode Island, United States

Abington Memorial Hospital; 🇺🇸 Abington, Pennsylvania, United States

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Sanford USD Medical Center - Sioux Falls; 🇺🇸 Sioux Falls, South Dakota, United States

Harrison HealthPartners Hematology and Oncology-Bremerton; 🇺🇸 Bremerton, Washington, United States

Harrison HealthPartners Hematology and Oncology-Poulsbo; 🇺🇸 Poulsbo, Washington, United States

Cancer Care Northwest - Spokane South; 🇺🇸 Spokane, Washington, United States

University of Washington Medical Center; 🇺🇸 Seattle, Washington, United States

HSHS Sacred Heart Hospital; 🇺🇸 Eau Claire, Wisconsin, United States

Marshfield Clinic-Minocqua Center; 🇺🇸 Minocqua, Wisconsin, United States

Diagnostic and Treatment Center; 🇺🇸 Weston, Wisconsin, United States

Freeman Health System; 🇺🇸 Joplin, Missouri, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

McFarland Clinic PC-Jefferson; 🇺🇸 Jefferson, Iowa, United States

Lawrence Memorial Hospital; 🇺🇸 Lawrence, Kansas, United States

Woman's Hospital; 🇺🇸 Baton Rouge, Louisiana, United States

Oklahoma Cancer Specialists and Research Institute-Tulsa; 🇺🇸 Tulsa, Oklahoma, United States

Rockwood Cancer Treatment Center-DHEC-Downtown; 🇺🇸 Spokane, Washington, United States

ProHealth D N Greenwald Center; 🇺🇸 Mukwonago, Wisconsin, United States

Ascension Saint Michael's Hospital; 🇺🇸 Stevens Point, Wisconsin, United States

Sarasota Memorial Hospital; 🇺🇸 Sarasota, Florida, United States

UH Seidman Cancer Center at Lake Health Mentor Campus; 🇺🇸 Mentor, Ohio, United States

Southern Ohio Medical Center; 🇺🇸 Portsmouth, Ohio, United States