Trial Outcomes & Findings for GM-CSF, Sargramostim in Women With Recurrent Ovarian Cancer (NCT NCT00157573)

Last Updated: 2017-05-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

72 participants

Primary outcome timeframe

Up to 460 days

Results posted on

2017-05-08

Participant Flow

Granulocyte macrophage colony-stimulating factor (GM-CSF) Phase II recruitment from oncology clinic.

Phase II

Participant milestones

Participant milestones
Measure	GM-CSF, Sargramostim Cohort 1 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.	GM-CSF, Sargramostim Cohort 2 GM-CSF, sargramostim 150 μg/m\^2 subcutaneous injection daily for 28 days in a 28-day cycle until disease progression or unacceptable toxicity for a 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 the white blood cell count.
Overall Study STARTED	35	37
Overall Study COMPLETED	35	37
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

GM-CSF, Sargramostim in Women With Recurrent Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GM-CSF, Sargramostim n=72 Participants All enrolled eligible participants who participated in Cohort 1 or Cohort 2 of the study. In Cohort 1 participants received 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. In Cohort 2 participants received GM-CSF, sargramostim 150 μg/m\^2 subcutaneous injection daily for 28 days in a 28-day cycle until disease progression or unacceptable toxicity for a 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	49 Participants n=5 Participants
Age, Categorical >=65 years	23 Participants n=5 Participants
Age, Continuous	60 years STANDARD_DEVIATION 9.15 • n=5 Participants
Sex: Female, Male Female	72 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	72 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 460 days

Population: After initial analysis, it was clear that the schedule did not significantly impact the immune response and that the actual white cell count (WCC) was the best correlate predictor of change in CA125, and so the cohorts were combined for an overall analysis. 1 participant withdrew consent and was not included in the analysis.

Outcome measures

Outcome measures
Measure	GM-CSF, Sargramostim n=71 Participants All enrolled eligible participants who participated in Cohort 1 or Cohort 2 of the study. In Cohort 1 participants received 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. In Cohort 2 participants received GM-CSF, sargramostim 150 μg/m\^2 subcutaneous injection daily for 28 days in a 28-day cycle until disease progression or unacceptable toxicity for a 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.
Median Time to Treatment Termination (TTT)	78 days Interval 14.0 to 460.0

SECONDARY outcome

Timeframe: Up to 60 months

Population: No analysis was performed. No data was reported for TTP in the clinical chart that was found to be reliable or consistent in the absence of proper computed tomography (CT) surveillance.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 60 months

Population: After initial analysis, it was clear that the schedule did not significantly impact the immune response and that the actual WCC was the best correlate predictor of change in CA125, and so the cohorts were combined for an overall analysis. 1 participant withdrew consent and was not included in the analysis.

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.

Outcome measures

Outcome measures
Measure	GM-CSF, Sargramostim n=71 Participants All enrolled eligible participants who participated in Cohort 1 or Cohort 2 of the study. In Cohort 1 participants received 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. In Cohort 2 participants received GM-CSF, sargramostim 150 μg/m\^2 subcutaneous injection daily for 28 days in a 28-day cycle until disease progression or unacceptable toxicity for a 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.
Tumor Response Rate (RR) Stable Disease	20 Participants
Tumor Response Rate (RR) Complete Response	1 Participants
Tumor Response Rate (RR) Partial Response	0 Participants
Tumor Response Rate (RR) Progressive Disease	50 Participants

SECONDARY outcome

Timeframe: Up to 460 days

Population: After initial analysis, it was clear that the schedule did not significantly impact the immune response and that the WCC was the best correlate predictor of change in CA125, and so the cohorts were combined for an overall analysis. 1 participant withdrew consent and was not included in the analysis.

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.

Outcome measures

Outcome measures
Measure	GM-CSF, Sargramostim n=72 Participants All enrolled eligible participants who participated in Cohort 1 or Cohort 2 of the study. In Cohort 1 participants received 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. In Cohort 2 participants received GM-CSF, sargramostim 150 μg/m\^2 subcutaneous injection daily for 28 days in a 28-day cycle until disease progression or unacceptable toxicity for a 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.
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Macular tuft	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Nausea sinus	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Thrombocytopenia	2 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Musculoskeletal pain	9 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Fatigue	3 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Abnormal liver function test	2 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Vomiting	2 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Metabolic	2 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Small bowel obstruction	2 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Myelodysplasia	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Urticaria	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Abdominal pain	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Palpitations	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Hypertension	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Changes in bowel habit	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Diverticulitis	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Gout	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Headache	1 Participants
Number of Participants With Adverse Events (Toxicity) Grade 3 or 4 Bradycardia	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 60 months

Population: This outcome measure was originally posted as a secondary outcome measures but was actually an exploratory endpoint. No data was collected.

Outcome measures

Outcome data not reported

Adverse Events

GM-CSF, Sargramostim Cohort 1

Serious events: 2 serious events

Other events: 35 other events

Deaths: 0 deaths

GM-CSF, Sargramostim Cohort 2

Serious events: 5 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GM-CSF, Sargramostim Cohort 1 n=35 participants at risk 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.	GM-CSF, Sargramostim Cohort 2 n=37 participants at risk GM-CSF, sargramostim 150 μg/m\^2 subcutaneous injection daily for 28 days in a 28-day cycle until disease progression or unacceptable toxicity for a median of 3 cycles. GM-CSF dose escalation was permitted up to 250 μg/m\^2 per day if applicable based on toxicity and white blood cell count.
Blood and lymphatic system disorders Myelodysplastic syndrome	0.00% 0/35 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)	2.7% 1/37 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)
Infections and infestations Diverticulitis	0.00% 0/35 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)	2.7% 1/37 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/35 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)	2.7% 1/37 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)
Cardiac disorders Bradycardia	0.00% 0/35 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)	2.7% 1/37 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)
Respiratory, thoracic and mediastinal disorders Difficulty breathing	0.00% 0/35 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)	2.7% 1/37 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)
Gastrointestinal disorders Bowel obstruction	5.7% 2/35 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)	0.00% 0/37 • Between December 2004 and October 2008, 72 eligible and evaluable patients were enrolled. Adverse events (AEs) were collected for 30 calendar days after administration of the last dose of trial drug (Up to 234 days)

Other adverse events

Additional Information

Richard T Penson MD MCCP

MGH DF/HCC

Phone: 617-726-8566

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place