Sargramostim and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Previous Chemotherapy

Phase 2

Completed

• Conditions: Ovarian Clear Cell Cystadenocarcinoma; Stage IV Ovarian Epithelial Cancer; Ovarian Endometrioid Adenocarcinoma; Peritoneal Cavity Cancer; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Brenner Tumor; Fallopian Tube Cancer; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma
• Interventions: Biological: sargramostim; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Other: laboratory biomarker analysis; Other: immunologic technique

• Registration Number: NCT00466960
• Lead Sponsor: University of Washington

Brief Summary

RATIONALE: Colony stimulating factors, such as sargramostim (GM-CSF), may stimulate the immune system in different ways and stop tumor cells from growing and may also increase the number of immune cells found in bone marrow or peripheral blood and help the immune system recover from the side effects of chemotherapy. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving GM-CSF together with paclitaxel albumin-stabilized nanoparticle formulation may be an effective treatment for ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.

PURPOSE: This phase II trial is studying how well giving GM-CSF together with paclitaxel albumin-stabilized nanoparticle formulation works in treating patients with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that did not respond to previous chemotherapy

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether chronic GM-CSF administration during and after cytotoxic chemotherapy with paclitaxel albumin-stabilized nanoparticle formulation can induce a longer remission than experienced in the most recent platinum-containing regimen.

SECONDARY OBJECTIVES:

I. To determine the extent to which chronic GM-CSF administration can increase the number of activated monocytes in patients with advanced stage epithelial ovarian cancer.

II. To determine the extent to which chronic GM-CSF administration can increase the number and activation state of peripheral circulating antigen presenting cells, such as dendritic cells and activated monocytes, in patients with advanced epithelial ovarian cancer.

III. To determine the extent to which chronic GM-CSF administration can increase the number and functional status of T cells that recognize tumor specific antigens in patients with advanced stage epithelial ovarian cancer.

IV. To determine the extent to which chronic GM-CSF administration can increase the number and functional status of antigen specific T cells that recognize foreign pathogens in patients with advanced stage epithelial ovarian cancer.

OUTLINE:

INDUCTION THERAPY: Patients receive GM-CSF subcutaneously (SC) once daily on days 16-26. Patients also receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 14 days after last GM-CSF injection, patients receive GM-CSF SC once daily on days 1-15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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

Study Timeline

• Study Start: 2006-05
• Study First Submitted: 2007-04-25
• Study First Submitted QC: 2007-04-25
• Study First Posted: 2007-04-27
• Primary Completion: 2011-07
• Results First Submitted: 2017-04-17
• Status Verified: 2017-07
• Results First Submitted QC: 2017-07-24
• Last Update Submitted: 2017-07-24
• Results First Posted: 2017-08-28
• Last Update Posted: 2017-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Patients must have histologically proven epithelial ovarian, fallopian tube or primary peritoneal malignancies, excluding tumors of low malignant potential (borderline)

• Patients with the following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified

• Patients must have either primary platinum refractory or resistant carcinoma or secondary platinum resistant disease:

  1. Primary platinum refractory disease is defined as progression of disease on initial platinum-based chemotherapy or persistent disease at the conclusion of the initial platinum-based chemotherapy course associated with the primary debulking surgery.
  2. Primary platinum resistant disease is defined as recurrence of carcinoma within 6 months (+ 14 days) of completion of initial platinum-based chemotherapy associated with the primary debulking surgery. (The 14 day window is to allow study entry for those patients where evidence clearly suggests that had an assessment been made early the patient would have met the 6 month time line. This will be determined by the study principal investigator [P.I.])
  3. Secondary platinum resistant disease is defined as meeting any one of the listed criteria during or following a subsequent platinum containing regimen.

• Patients must have an elevated serum cancer antigen (CA)125 on two occasions greater than 7 days apart

• Absolute neutrophil count >= 1500/uL

• Platelets >= 100,000/uL

• Creatinine =< 2.0 mg/dL

• Total bilirubin =< 1.5 mg/dL (unless history of Gilbert's disease)

• Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x upper limit of normal (ULN) or < 5 x ULN with documented report of hepatic metastases

• Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least three weeks must have elapsed since prior chemotherapy or radiation therapy

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Exclusion Criteria

• Patient has an allergic history to paclitaxel or GM-CSF, not manageable by pre-medication and/or slow drug infusion
• Patient has poorly controlled arrhythmias or unstable coronary artery disease or has had a myocardial infarction within the last six months
• Patient with active pulmonary edema or pleural effusion
• Active infection requiring IV antibiotics
• Patient currently requires lithium, (due to drug interaction with GM-CSF [Leukine])
• Patient currently presents with a neurotoxicity > Grade 1
• Women of childbearing potential
• Patients with a history of other invasive malignancies, within the previous 5 years are excluded, with the exception of non-melanoma skin cancer

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (colony stimulating factor and chemotherapy)	paclitaxel albumin-stabilized nanoparticle formulation	INDUCTION THERAPY: Patients receive GM-CSF SC once daily on days 16-26. Patients also receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 14 days after last GM-CSF injection, patients receive GM-CSF SC once daily on days 1-15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Treatment (colony stimulating factor and chemotherapy)	immunologic technique	INDUCTION THERAPY: Patients receive GM-CSF SC once daily on days 16-26. Patients also receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 14 days after last GM-CSF injection, patients receive GM-CSF SC once daily on days 1-15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Treatment (colony stimulating factor and chemotherapy)	laboratory biomarker analysis	INDUCTION THERAPY: Patients receive GM-CSF SC once daily on days 16-26. Patients also receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 14 days after last GM-CSF injection, patients receive GM-CSF SC once daily on days 1-15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Treatment (colony stimulating factor and chemotherapy)	sargramostim	INDUCTION THERAPY: Patients receive GM-CSF SC once daily on days 16-26. Patients also receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 14 days after last GM-CSF injection, patients receive GM-CSF SC once daily on days 1-15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Response Rate	Up to 5 years	Number of patients achieving a complete or partial response.
Time to Progression	Up to 5 years	Median time to progression

Secondary Outcome Measures

Name	Time	Method
Correlation Between Circulating Dendritic Cell Count and Maturation State With Clinical Response and Response Duration	Up to 5 years	Baseline median percentages of CD45+ cells made up of myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) in complete responders (CR) compared to partial and non-responders (PR+NR+SD).
Precursor Frequency of Circulating Activated T Lymphocytes Against Common Ovarian Cancer Tumor Associated Antigens to Measure the Development of Immunity to Anti-tumor Antigens	Up to 5 years	Correlation of time to progression and change in circulating activated T lymphocytes from baseline to follow-up.
Correlation Between Circulating Monocytes and Time to Progression	Up to 5 years	Baseline median percentages of CD45+ cells made up of monocytes in complete responders (CR) compared to partial-responders, non-responders and those with stable disease (PR+NR+SD).
Precursor Frequency of Circulating T Lymphocytes Activated Against Foreign Antigens	Up to 5 years	Correlation of time to progression and change in circulating activated T lymphocytes from baseline to follow-up.

Trial Locations

Locations (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States