VTX-2337 and Pegylated Liposomal Doxorubicin (PLD) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
- Conditions
- Epithelial Ovarian CancerFallopian Tube CancerPrimary Peritoneal Cancer
- Interventions
- Registration Number
- NCT01666444
- Lead Sponsor
- Celgene
- Brief Summary
The purpose of this study is to compare the overall survival of patients treated with VTX-2337 + pegylated liposomal doxorubicin (PLD) versus those treated with PLD alone in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer.
VTX-2337, a small molecule agonist of Toll-like Receptor 8 (TLR8), activates multiple components of the innate immune system and is being developed as a novel therapeutic agent for use in oncology. Experimental data obtained in an animal model of ovarian cancer supports the combination of VTX-2337 with PLD. In this model, the combination of VTX-2337 and PLD resulted in a significant reduction in tumor growth compared to either agent alone and an increase in the number of T lymphocytes infiltrating the tumor. The combination of PLD and VTX-2337 has been tested in a small number of women with ovarian cancer in a Phase 1b study and appears to be generally well-tolerated.
- Detailed Description
OBJECTIVES
Primary Objectives:
* To compare the overall survival (OS) of patients treated with VTX-2337 + PLD versus those treated with PLD alone in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer.
* To compare the progression-free survival (PFS) between the two treatment groups using Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST).
Secondary Objectives:
* To compare the progression-free survival (PFS) between the two treatment groups using Response Evaluation Criteria In Solid Tumors (RECIST 1.1).
* To compare the nature, frequency and severity of drug-related adverse events (AEs) between the two treatment groups.
Exploratory Objectives:
* To compare the best overall response rate (ORR) and duration of response (based on the probability of being in response function \[PBRF\]) between the two treatment groups using irRECIST and RECIST 1.1.
* To compare the disease control rate (DCR) between the two treatment groups using irRECIST and RECIST 1.1.
* To assess the impact of immune status and response on the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment.
* To assess the effect of TLR8 polymorphisms and BRCA1/BRCA2 mutations on the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment.
* To assess the effect of immune cell subsets, as measured by immunohistochemistry and micro RNA in primary tumor tissue (e.g. immune score), on the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment.
* To assess whether the presence of autoantibodies to tumor-derived proteins are predictive of the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment.
OUTLINE:
This is Phase 2 multicenter clinical study to evaluate the efficacy and safety of the combination of VTX-2337 + PLD compared to PLD + Placebo.
The dosing schedule will be the same for both treatment arms, and will be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 or placebo on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus VTX-2337 or placebo on Day 3.
Blood samples are collected periodically during cycle 1 for pharmacodynamics, pharmacogenomics, and other research studies.
Patients will receive therapy until disease progression based on Immune-Related RECIST or until adverse effects prohibit further therapy. Following treatment completion, all patients will be followed with physical exams and histories every three months for the first two years, and then every six months for the next three years, and then
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 297
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Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
-
Patients with the following histologic cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, malignant Brenner's tumor or adenocarcinoma not otherwise specified.
-
Patient must have measurable disease as defined by RECIST 1.1.
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Patients must have received treatment with a 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, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment.
Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease.
Patients are allowed to have received, but are not required to have received, biologic/targeted therapy (e.g., bevacizumab and/or PARP inhibitor) as part of their primary treatment regimen or for management of recurrent or persistent disease.
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Patients must have platinum-resistant disease, defined as having a platinum-free interval (PFI) of < 12 months after first- or second-line platinum-based chemotherapy, or having disease progression while receiving second-line platinum-based chemotherapy.
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Patients must have adequate bone marrow, renal, hepatic, and neurologic functions as defined by the following:
- Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3. This ANC cannot have been induced or supported by granulocyte colony stimulating factors. Platelets ≥ 100,000/mm3. Hemoglobin ≥ 9 g/dL.
- Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN).
- Hepatic function: bilirubin < 1.2 mg/dL, SGOT (AST) and SGPT (ALT) ≤ 3.0 x ULN and alkaline phosphatase ≤ 2.5 x ULN.
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Patients must have recovered from effects of recent surgery, radiotherapy or chemotherapy:
- Patients should be free of active infection requiring parenteral antibiotics.
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy is permitted.
- Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted agents and immunologic agents, must be discontinued at least three weeks prior to registration.
- Any prior radiation therapy must be completed at least four weeks prior to registration.
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Patients must have a GOG performance status of 0 or 1.
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Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. If applicable, patients must discontinue breastfeeding prior to study entry.
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Patients must meet the entry requirements and undergo the baseline procedures.
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Patients must have signed an IRB-approved informed consent form and authorization permitting release of personal health information.
- Patients who have had treatment with VTX-2337, doxorubicin, PLD, or any other anthracycline.
- Patients who have received an investigational agent < 30 days prior to registration.
- Patients who have received oral or parenteral corticosteroids < 2 weeks prior to registration or who require ongoing systemic immunosuppressive therapy for any reason.
- Patients with active autoimmune disease. "Active" refers to any condition currently requiring therapy. Examples of autoimmune disease include systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis.
- Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of the other malignancy being present within the last three years.
- Patients who have received prior radiotherapy OTHER THAN for the treatment of ovarian, fallopian tube or primary peritoneal cancer within the last three years are excluded.
- Patients who have received prior chemotherapy OTHER THAN for the treatment of ovarian, fallopian tube or primary peritoneal cancer within the last three years are excluded.
- Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study.
- Patients with clinically significant cardiovascular disease.
- Patients who are pregnant or nursing.
- Patients under the age of 18.
- Patients with clinical symptoms or signs of gastrointestinal obstruction and/or who require parenteral hydration or nutrition.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PLD 40 mg/m2 plus placebo Placebo The dosing schedule will be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus placebo on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus placebo on Day 3 only. PLD 40 mg/m2 plus VTX-2337 VTX-2337 The dosing schedule will be be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus VTX-2337 on Day 3 only, without additional doses of VTX-2337 on Days 10 and Day 17. PLD 40 mg/m2 plus placebo pegylated liposomal doxorubicin (PLD) The dosing schedule will be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus placebo on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus placebo on Day 3 only. PLD 40 mg/m2 plus VTX-2337 pegylated liposomal doxorubicin (PLD) The dosing schedule will be be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus VTX-2337 on Day 3 only, without additional doses of VTX-2337 on Days 10 and Day 17.
- Primary Outcome Measures
Name Time Method Overall Survival Survival is measured from date of enrollment and randomization on the study until death from any cause, or if alive at last contact, date of last contact. Comparison of duration of survival between the 2 treatment groups
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) Progression-free survival is measured from enrollment and randomization on the study until first indication of progression based on irRECIST criteria or death from any cause, or if progression-free at last contact, the date of last disease assessment. Comparison of PFS between the 2 treatment groups
Frequency and Severity of Adverse Events (AEs) Assessed during each cycle of therapy and within 30 days after the last cycle of therapy An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE can be unfavorable and unintended sign, symptom, or disease which is temporally associated with the use of investigational product (IP), whether or not considered related to the IP. A serious AE = an AE occurring at any dose that: • Results in death • Is life- threatening • Requires or prolongs existing inpatient hospitalization • Results in persistent or significant disability/incapacity • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to IP and graded the severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0: Grade (GR) 1 = Mild; asymptomatic or mild symptoms; GR 2 = Moderate (minimal, local or noninvasive intervention indicated); GR 3 = Severe or medically significant; GR 4 = Life-threatening; GR 5 = Death
Trial Locations
- Locations (127)
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States
Johns Hopkins Medical Institution
🇺🇸Baltimore, Maryland, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
St. Dominic-Jackson Memorial Hospital
🇺🇸Jackson, Mississippi, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Reed City Hospital - Spectrum Health
🇺🇸Reed City, Michigan, United States
Mercy Health Partners - Mercy Campus
🇺🇸Muskegon, Michigan, United States
Cooper University Hospital
🇺🇸Camden, New Jersey, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Gynecologic Oncology of Central New York - SUNY Upstate
🇺🇸Syracuse, New York, United States
Women's Cancer Center at Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Bon Secours St. Francis Hospital
🇺🇸Greenville, South Carolina, United States
Green Bay Oncology at St. Vincent's Hospital
🇺🇸Green Bay, Wisconsin, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Northwestern University - Robert H. Lurie Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The Methodist Hospital
🇺🇸Houston, Texas, United States
Pacific Gynecology Specialists
🇺🇸Seattle, Washington, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Kaiser Permanente Medical Center
🇺🇸Walnut Creek, California, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
The Hospital of Central Connecticut
🇺🇸New Britain, Connecticut, United States
Northeast Georgia Medical Center
🇺🇸Gainesville, Georgia, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Lahey Hospital & Medical Center
🇺🇸Burlington, Massachusetts, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Grand Rapids Clinical Oncology
🇺🇸Grand Rapids, Michigan, United States
Gynecologic Oncology of West Michigan
🇺🇸Grand Rapids, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Summa Health System
🇺🇸Akron, Ohio, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Bay Area Medical Center
🇺🇸Marinette, Wisconsin, United States
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
St. Vincent Gynecologic Oncology
🇺🇸Indianapolis, Indiana, United States
Women's Cancer Care Center of Nevada
🇺🇸Las Vegas, Nevada, United States
Providence Saint Joseph Medical Center
🇺🇸Burbank, California, United States
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Central Georgia Gynecologic Oncology
🇺🇸Macon, Georgia, United States
Georgia Regents University
🇺🇸Augusta, Georgia, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
St. Joseph's - Candler Gynecologic Oncology
🇺🇸Savannah, Georgia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Sudarshan K. Sharma, MD, LTD
🇺🇸Hinsdale, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
McFarland Clinic
🇺🇸Ames, Iowa, United States
Ellis Fischel Cancer Center - University of Missouri
🇺🇸Columbia, Missouri, United States
Memorial Medical Center
🇺🇸Las Cruces, New Mexico, United States
Women's Cancer Care Associates
🇺🇸Albany, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
SUNY Downstate Medical Center
🇺🇸Brooklyn, New York, United States
NYU Langone Medical Center - Cancer Institute
🇺🇸New York, New York, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Monter Cancer Center
🇺🇸Lake Success, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Hope Women's Cancer Center
🇺🇸Asheville, North Carolina, United States
Carolinas Medical Center / Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Alamance Regional Cancer Center
🇺🇸Burlington, North Carolina, United States
Carolinas Medical Center - Northeast
🇺🇸Concord, North Carolina, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Fairview Hospital Moll Pavilion Cancer Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Tulsa Cancer Institute
🇺🇸Tulsa, Oklahoma, United States
Hillcrest Hospital - Cleveland Clinic
🇺🇸Mayfield Heights, Ohio, United States
Lake University Seidman Cancer Center
🇺🇸Mentor, Ohio, United States
Abington Memorial Hospital; Hanjani Institute for Gynecologic Oncology
🇺🇸Abington, Pennsylvania, United States
University of Pennsylvania Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Hillman Cancer Center - University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Western Pennsylvania Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Reading Hospital (McGlinn Family Regional Cancer Center)
🇺🇸West Reading, Pennsylvania, United States
Women and Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Carilion Clinic Gynecological Oncology
🇺🇸Roanoke, Virginia, United States
Mid Atlantic Pelvic Surgery Associates
🇺🇸Annandale, Virginia, United States
Northwest Hospital - UW Medicine
🇺🇸Seattle, Washington, United States
Women's Cancer Care of Seattle
🇺🇸Seattle, Washington, United States
Abbott Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Huntsman Cancer Institute, University of Utah
🇺🇸Salt Lake City, Utah, United States
Minnesota Oncology Coon Rapids Clinic
🇺🇸Coon Rapids, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Woodbury Clinic - CornerStone Medical Specialty Centre
🇺🇸Woodbury, Minnesota, United States
Minnesota Oncology Hematology - St. Paul Cancer Center
🇺🇸Saint Paul, Minnesota, United States
Metro Minnesota Clinical Oncology Program
🇺🇸Saint Louis Park, Minnesota, United States
Park Nicollet Frauenshuh Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
Winthrop P. Rockefeller Cancer Institute - University of Arkansas
🇺🇸Little Rock, Arkansas, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
St. Francis Hospital and Medical Center
🇺🇸Hartford, Connecticut, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
St Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
University of Massachusetts Memorial Healthcare
🇺🇸Worcester, Massachusetts, United States
Maine Medical Partners Women's Health
🇺🇸Scarborough, Maine, United States
Holy Family Memorial Medical Center
🇺🇸Manitowoc, Wisconsin, United States
Women's Cancer Associates
🇺🇸Saint Petersburg, Florida, United States
Saint Mary's Health Care
🇺🇸Grand Rapids, Michigan, United States
Gibbs Cancer Center
🇺🇸Spartanburg, South Carolina, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Karmanos Cancer Institute - Wayne State University
🇺🇸Detroit, Michigan, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Peggy and Charles Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Aurora St. Luke's Medical Center Gynecologic Oncology
🇺🇸Milwaukee, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Sutter Cancer Center
🇺🇸Sacramento, California, United States
St. Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
MD Anderson Cancer Center - Orlando
🇺🇸Orlando, Florida, United States
Wake Forest University Health Science
🇺🇸Winston-Salem, North Carolina, United States
Yale - New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Virginia Gynecology Oncology
🇺🇸Richmond, Virginia, United States
Green Bay Oncology at St. Mary's Hospital
🇺🇸Green Bay, Wisconsin, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
University of Wisconsin-Madison
🇺🇸Madison, Wisconsin, United States
Southwest Gynecologic Oncology Associates
🇺🇸Albuquerque, New Mexico, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
University of Kansas Medical Center
🇺🇸Westwood, Kansas, United States