GM-CSF, Sargramostim in Women With Recurrent Ovarian Cancer

Study Overview
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Brief Summary
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Granulocyte macrophage colony-stimulating factor (GM-CSF) is an immunostimulant and preliminary data suggests it may change the natural history of prostate cancer and melanoma. This study looks at ability of GM-CSF to alter disease progression in women who have recurrent but asymptomatic recurrence of their ovarian cancer.

Detailed Description
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This is an open labeled, single arm phase II study of GM-CSF, sargramostim delivered daily without a break in a population of healthy and fit women with evidence of recurrent but asymptomatic mullerian malignancy (such as ovarian cancer, fallopian tube cancer, or primary peritoneal cancer). The main goal is to determine the time to treatment termination due to disease progression or toxicity.

Official Title
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Phase II Trial of GM-CSF in Women With Asymptomatic Ovarian, Primary Peritoneal, or Tubal Carcinoma

Conditions
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Ovarian Cancer, Fallopian Tube Cancer

Intervention / Treatment
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* Drug: GM-CSF, sargramostim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a history of histologic or cytologic diagnosis of primary ovarian, primary peritoneal or tubal carcinoma. Patients must be asymptomatic from their cancer. Patients must have evidence of recurrent carcinoma, as determined by: A rising cancer antigen 125 (CA-125) serum level greater than 35 U/mL or two successive rising values with the most recent value at least 3 times the nadir value. Or evidence of evaluable or measurable disease by x-ray or computed tomography (CT) scan. Patients may not receive concurrent antineoplastic therapy. All hormonal therapy used as a treatment modality (i.e. tamoxifen, arimidex, etc) must be stopped prior to treatment on protocol. Age > 18 years. Eastern Cooperative Oncology Group (ECOG) performance status < 2. Exclusion Criteria: Known severe hypersensitivity to GM-CSF. Other coexisting malignancies or malignancies diagnosed within the last 5 years, with the exception of basal cell carcinoma or cervical cancer in situ or concurrent superficial or stage IB endometrial carcinoma. Concomitant use of anti-neoplastic therapy. Treatment with a non-FDA approved or investigational drug within 30 days before Day 1 of trial treatment. Any unresolved chronic toxicity greater then Common Toxicity Criteria (CTC) grade 2 from previous anticancer therapy (except alopecia). Serum creatinine level greater than CTC grade 2 [1.5 x upper limit normal (ULN)]. Pregnancy or breast feeding (women of childbearing potential). Severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) as judged by the investigator. Significant clinical disorder or laboratory finding that makes it potentially unsafe for the subject to participate in the trial as judged by the investigator. Patients currently receiving other investigational antineoplastic agents, on systemic chemotherapy or under radiation therapy treatment. Patients with clinical and/or radiographic evidence of current or impending bowel obstruction. Performance status < 1. Ability to understand and the willingness to sign a written informed consent document.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GM-CSF, Sargramostim Cohort 1<br>GM-CSF, Sargramostim 250 μg/m^2 subcutaneous injection daily on days 1 to 14 in a 28-day cycle until disease progression or unacceptable toxicity for a median of 3 cycles. | Drug: GM-CSF, sargramostim<br>* GM-CSF subcutaneous injection<br>* Other names: Leukine®;|
| Experimental: GM-CSF, Sargramostim Cohort 2<br>GM-CSF, sargramostim 150 μg/m^2 subcutaneous injection daily for 28 days in a 28-day cycle until disease progression or unacceptable toxicity fora median of 3 cycles. GM-CSF, sargramostim dose escalation was permitted up to 250 μg/m^2 per day if applicable based on toxicity and white blood cell count. | Drug: GM-CSF, sargramostim<br>* GM-CSF subcutaneous injection<br>* Other names: Leukine®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Treatment Termination (TTT) | TTT is the median time in days to discontinuing treatment with GM-CSF, sargramostim (treatment termination) e.g. time on study until progression of disease, unacceptable adverse effects, bowel obstruction, development of new ascites or pleural effusions, initiation of systemic chemotherapy, participant death, development of co-morbid diseases which make participant continuation on the trial unsafe in the judgment of the principal investigator or the treating physician or withdrawal of consent by the participant. | Up to 460 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Progression (TTP) | TTP was defined as the median time in days from trial entry until progressive disease (PD) was documented as defined by RECIST criteria. PD was defined of at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. In participants with no measurable disease who had an informative cancer antigen-125 (CA-125), PD was defined as a rise of > 50% over Baseline, confirmed by a subsequently higher value at least 21 days later. | Up to 60 months | 
| Tumor Response Rate (RR) | RR is the percentage of patients with response as assessed by the investigator using Response Evaluable Criteria in Solid Tumors (RECIST) and CA-125 Rustin criteria. Complete Response (CR) is the disappearance of all target and non-target lesions and normalization of CA-125. Partial Response (PR) is at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; in patients with no measurable disease with an informative CA-125, the 75% definitions by Rustin is used. Stable Disease is neither sufficient shrinkage for PR nor increase for PD, taking as reference the smallest sum LD since the treatment start. PD is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since treatment start or the appearance of one or more new lesions; in patients with no measurable disease with an informative CA-125, PD is defined as a rise of > 50% over baseline, confirmed by a higher value 21 days later. | Up to 60 months | 
| Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 | Adverse Events (previously toxicity) were graded according the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0. The total number of participants with adverse events graded 3 (severe) or 4 (life-threatening or disabling) are reported. | Up to 460 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asymptomatic, Clinical trial, Phase II, GM-CSF, Immunotherapy