Trial Outcomes & Findings for Ph II Study of Wkly Topotecan + Bevacizumab in Plat. Resistant/Recurrent Gyn Cancers (NCT NCT00343044)

Last Updated: 2015-05-15

Results Overview

Progression free survival(PFS)was measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients with measurable disease. For patients with nonmeasurable disease, cancer antigen (CA-125) levels were used to determine response according to Rustin criteria. Progression-free survival was defined as number of months after beginning study treatment until progressive disease or death, respectively.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

PFS and OS were defined as the number of months after commencing study treatment until progressive disease or death.

Results posted on

2015-05-15

Participant Flow

Subjects enrolled from August 2006 to November 2008, in the medical oncoogy practices at Virginia Mason Medical Center and the Puget Sound Oncology Consortium in Seattle, WA.

Women had advanced or recurrent epithelial ovarian, peritoneal, or fallopian tube cancer. Enrollment was restricted to women who had received a maximum of two prior chemotherapy regimens, with at least one prior primary taxane and platinum-based therapy.

Participant milestones

Participant milestones
Measure	Combined Weekly Topotecan and Biweekly Bevacizumab Treatment was administered in 28 day cycles, with IV bevacizumab 10 mg/kg given on days 1 and 15 and IV topotecan 4 mg/m2 given on days 1 and 8. Treatment was continued until progressive disease defined by RECIST, symptomatic deterioration related to clinical progression, excessive toxicity. Dose reductions of bevacizumab were not permitted.
Overall Study STARTED	40
Overall Study COMPLETED	40
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ph II Study of Wkly Topotecan + Bevacizumab in Plat. Resistant/Recurrent Gyn Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Combined Weekly Topotecan and Biweekly Bevacizumab n=40 Participants Treatment was administered in 28 day cycles, with IV bevacizumab 10 mg/kg given on days 1 and 15 and IV topotecan 4 mg/m2 given on days 1 and 8. Treatment was continued until progressive disease defined by RECIST, symptomatic deterioration related to clinical progression, excessive toxicity. Dose reductions of bevacizumab were not permitted.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	37 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Age, Continuous	58.6 years STANDARD_DEVIATION 11.31 • n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	40 participants n=5 Participants

PRIMARY outcome

Timeframe: PFS and OS were defined as the number of months after commencing study treatment until progressive disease or death.

Population: This was determined assuming a median progression free survival of 9 months and an analysis calculating the sample size at which the narrowing of its 95% confidence interval became greater than .20 for every 2 patients added. Progression free survival and overall survival were estimated by using the Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Combined Weekly Topotecan and Biweekly Bevacizumab n=40 Participants Treatment was administered in 28 day cycles, with IV bevacizumab 10 mg/kg given on days 1 and 15 and IV topotecan 4 mg/m2 given on days 1 and 8. Treatment was continued until progressive disease defined by RECIST, symptomatic deterioration related to clinical progression, excessive toxicity. Dose reductions of bevacizumab were not permitted.
Progression Free Survival All participants	7.8 months Interval 3.0 to 9.4
Progression Free Survival One prior regimen (n=21)	2.8 months Interval 2.3 to 7.2
Progression Free Survival Two prior regimens (n=19)	10.9 months Interval 7.1 to 14.7

SECONDARY outcome

Timeframe: PFS and OS were defined as the number of months after commencing study treatment until progressive disease or death.

Population: The planned enrollment of 40 participants was determined using a median PFS of 9 months (based on a median PFS of 7.2 months in a previous trial).

Overall survival was defined as the number of months after commencing study treatment to death.

Outcome measures

Outcome measures
Measure	Combined Weekly Topotecan and Biweekly Bevacizumab n=40 Participants Treatment was administered in 28 day cycles, with IV bevacizumab 10 mg/kg given on days 1 and 15 and IV topotecan 4 mg/m2 given on days 1 and 8. Treatment was continued until progressive disease defined by RECIST, symptomatic deterioration related to clinical progression, excessive toxicity. Dose reductions of bevacizumab were not permitted.
Evaluation of Overall Survival All Participants	16.6 months Interval 12.8 to 22.9
Evaluation of Overall Survival One Prior Regimen (n=21)	12.8 months Interval 9.0 to 14.9
Evaluation of Overall Survival Two Prior Regimens (n=19)	22.9 months Interval 16.6 to 22.9

SECONDARY outcome

Timeframe: Response

RECIST criteria

Outcome measures

Outcome measures
Measure	Combined Weekly Topotecan and Biweekly Bevacizumab n=40 Participants Treatment was administered in 28 day cycles, with IV bevacizumab 10 mg/kg given on days 1 and 15 and IV topotecan 4 mg/m2 given on days 1 and 8. Treatment was continued until progressive disease defined by RECIST, symptomatic deterioration related to clinical progression, excessive toxicity. Dose reductions of bevacizumab were not permitted.
Objective Response Rate	10 participants

SECONDARY outcome

Timeframe: measured at each treatment cycle

Outcome measures

Outcome measures
Measure	Combined Weekly Topotecan and Biweekly Bevacizumab n=40 Participants Treatment was administered in 28 day cycles, with IV bevacizumab 10 mg/kg given on days 1 and 15 and IV topotecan 4 mg/m2 given on days 1 and 8. Treatment was continued until progressive disease defined by RECIST, symptomatic deterioration related to clinical progression, excessive toxicity. Dose reductions of bevacizumab were not permitted.
Number or Participants With Toxicity	40 participants

Adverse Events

Arm 1

Serious events: 9 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm 1 n=40 participants at risk Patients (N=40)
General disorders Pain	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Gastrointestinal disorders Bowel obstruction	10.0% 4/40 • Number of events 4 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Cardiac disorders Myocardial infarction	5.0% 2/40 • Number of events 2 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Cardiac disorders Hypotension	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Vascular disorders Venous thrombosis	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.

Other adverse events

Other adverse events
Measure	Arm 1 n=40 participants at risk Patients (N=40)
Blood and lymphatic system disorders Neutropenia	55.0% 22/40 • Number of events 22 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Blood and lymphatic system disorders Anemia	47.5% 19/40 • Number of events 19 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Blood and lymphatic system disorders Leukopenia	40.0% 16/40 • Number of events 16 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Blood and lymphatic system disorders Thrombocytopenia	32.5% 13/40 • Number of events 13 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
General disorders Fatigue	50.0% 20/40 • Number of events 20 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
General disorders Pain	45.0% 18/40 • Number of events 18 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Gastrointestinal disorders Nausea/Vomiting/Diarrhea	45.0% 18/40 • Number of events 18 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Infections and infestations infection	40.0% 16/40 • Number of events 16 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Psychiatric disorders Depression	7.5% 3/40 • Number of events 3 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Cardiac disorders Hypertension	30.0% 12/40 • Number of events 12 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Investigations GGT increased	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Psychiatric disorders Insomnia	7.5% 3/40 • Number of events 3 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Musculoskeletal and connective tissue disorders Musculoskeletal	12.5% 5/40 • Number of events 5 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Skin and subcutaneous tissue disorders Pruritus	5.0% 2/40 • Number of events 2 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Nervous system disorders Vasovagal reaction	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Renal and urinary disorders Proteinuria	7.5% 3/40 • Number of events 3 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Vascular disorders Venous thrombosis	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Blood and lymphatic system disorders Bleeding	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Psychiatric disorders Anxiety	5.0% 2/40 • Number of events 2 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Nervous system disorders Headache	7.5% 3/40 • Number of events 3 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Gastrointestinal disorders Constipation	10.0% 4/40 • Number of events 4 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Gastrointestinal disorders Bloating	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Gastrointestinal disorders Gastroesophageal reflux	5.0% 2/40 • Number of events 2 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Metabolism and nutrition disorders Dehydration	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Metabolism and nutrition disorders Anorexia	5.0% 2/40 • Number of events 2 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Gastrointestinal disorders Oral mucositis	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
General disorders Malaise	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
General disorders Chills	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Investigations Weight loss	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Respiratory, thoracic and mediastinal disorders Atelectasis	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.0% 2/40 • Number of events 2 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Respiratory, thoracic and mediastinal disorders Cough	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.5% 3/40 • Number of events 3 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Investigations Alkaline phosphatase	5.0% 2/40 • Number of events 2 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Investigations Aspartate aminotransferase	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Investigations Alanine aminotransferase	5.0% 2/40 • Number of events 2 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Metabolism and nutrition disorders Hyponatremia	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Metabolism and nutrition disorders Hypokalemia	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Metabolism and nutrition disorders Hypophosphatemia	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Metabolism and nutrition disorders Hyperglycemia	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Investigations Cholesterol high	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Skin and subcutaneous tissue disorders Dry skin	2.5% 1/40 • Number of events 1 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.0% 2/40 • Number of events 2 • Adverse event collecting occurred from first subject enrolled through January 31, 2010. All patients had been previously treated with platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel. Toxicity was generally mild or moderate. No treatment related death occurred.

Additional Information

Thomas Malpass, M.D., Principal Investigator

Benaroya Research Institute at Virginia Mason

Phone: 206-223-6193

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place