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Pembrolizumab, Bevacizumab, and Cyclophosphamide in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

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ClinicalTrials.gov Identifier: NCT02853318
Recruitment Status : Completed
First Posted : August 2, 2016
Results First Posted : November 6, 2020
Last Update Posted : October 6, 2021
Sponsor:
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Fallopian Tube Clear Cell Adenocarcinoma
Fallopian Tube Endometrioid Adenocarcinoma
Fallopian Tube Mucinous Adenocarcinoma
Fallopian Tube Serous Adenocarcinoma
Ovarian Clear Cell Adenocarcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Mucinous Adenocarcinoma
Ovarian Serous Adenocarcinoma
Primary Peritoneal Serous Adenocarcinoma
Recurrent Fallopian Tube Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Primary Peritoneal Carcinoma
Undifferentiated Fallopian Tube Carcinoma
Undifferentiated Ovarian Carcinoma
Interventions Biological: Bevacizumab
Drug: Cyclophosphamide
Other: Laboratory Biomarker Analysis
Biological: Pembrolizumab
Enrollment 40
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Hide Arm/Group Description

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide PO QD on days 1-21. Treatment repeats every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Cyclophosphamide: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Period Title: Overall Study
Started 40
Completed 39
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Arm/Group Title Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Hide Arm/Group Description

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide PO QD on days 1-21. Treatment repeats every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Cyclophosphamide: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants
62.2  (9.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
40
 100.0%
Male
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
White
38
  95.0%
Black
0
   0.0%
Other
2
   5.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 40 participants
40
ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
0
28
  70.0%
1
12
  30.0%
[1]
Measure Description:

0: Fully active, able to carry on all pre-disease performance without restriction.

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.
  2. Ambulatory and capable of all self-care but unable to carry out any work activities.
  3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
  4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
  5. Dead
BRCA mutation status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
positive
14
  35.0%
negative
23
  57.5%
unknown
3
   7.5%
[1]
Measure Description: The mutation status includes germline and somatic mutations.
Baseline PDL1 expression  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
positive
19
  47.5%
negative
17
  42.5%
unknown
4
  10.0%
1.Primary Outcome
Title Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events
Hide Description The highest observed adverse event will be tabulated by grade across all dose levels and cycles.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Hide Arm/Group Description:

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide PO QD on days 1-21. Treatment repeats every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Cyclophosphamide: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
No Adverse Events
1
   2.5%
Grade I
9
  22.5%
Grade II
20
  50.0%
Grade III
9
  22.5%
Grade IV
1
   2.5%
Grade V
0
   0.0%
2.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description Will be summarized using standard Kaplan-Meier methods, with estimates of median survival and given survival rates will be obtained with 90% confidence intervals.
Time Frame Time from the start of the study treatment until PFS event, assessed up to 1 year after the last subject enrolls
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Hide Arm/Group Description:

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide PO QD on days 1-21. Treatment repeats every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Cyclophosphamide: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Overall Number of Participants Analyzed 40
Median (90% Confidence Interval)
Unit of Measure: months
10.0
(6.5 to 17.4)
3.Secondary Outcome
Title Duration of Overall Survival
Hide Description Will be summarized using standard Kaplan-Meier methods, with estimates of median survival and given survival rates will be obtained with 90% confidence intervals.
Time Frame Up to 1 year after enrollment of the last subject
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Hide Arm/Group Description:

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide PO QD on days 1-21. Treatment repeats every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Cyclophosphamide: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Overall Number of Participants Analyzed 40
Median (90% Confidence Interval)
Unit of Measure: months
16.0
(12.5 to 26.1)
4.Secondary Outcome
Title An Anti-tumor Immune Response in Circulation and Tumor Tissue
Hide Description Assessed with immunohistochemistry (IHC), Nannostring, Flow Cytometry and Luminex assay.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The IHC, Nannostring, Flow Cytometry and Luminex assays were not completed.
Arm/Group Title Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Hide Arm/Group Description:

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide PO QD on days 1-21. Treatment repeats every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Cyclophosphamide: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Objective Tumor Response Assessed by Modified RECIST Version 1.1 Criteria
Hide Description

Frequency of response will be summarized with a 90% confidence interval.

An objective response is defined as a CR or PR, while a non-responder is defined as a SD or PD.

Time Frame Up to 6 months after enrollment start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Hide Arm/Group Description:

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide PO QD on days 1-21. Treatment repeats every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Cyclophosphamide: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Overall Number of Participants Analyzed 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.475
(0.349 to 0.603)
Time Frame Adverse Events: Through study completion up to 3 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Hide Arm/Group Description

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide PO QD on days 1-21. Treatment repeats every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Cyclophosphamide: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

All-Cause Mortality
Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Affected / at Risk (%)
Total   27/40 (67.50%)    
Hide Serious Adverse Events
Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Affected / at Risk (%) # Events
Total   0/40 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Pembrolizumab, Bevacizumab, Cyclophosphamide)
Affected / at Risk (%) # Events
Total   38/40 (95.00%)    
Blood and lymphatic system disorders   
Lymphadenopathy   1/40 (2.50%)  1
Endocrine disorders   
Hypothyroidism   4/40 (10.00%)  4
Eye disorders   
Eye pruritus   1/40 (2.50%)  1
Gastrointestinal disorders   
Abdominal distension   3/40 (7.50%)  3
Abdominal pain   2/40 (5.00%)  2
Abdominal pain upper   1/40 (2.50%)  1
Constipation   2/40 (5.00%)  2
Diarrhoea   14/40 (35.00%)  20
Dry mouth   1/40 (2.50%)  1
Dyspepsia   1/40 (2.50%)  1
Gastrooesophageal reflux disease   1/40 (2.50%)  1
Gingival bleeding   1/40 (2.50%)  1
Loose tooth   1/40 (2.50%)  1
Nausea   9/40 (22.50%)  10
Oral dysaesthesia   1/40 (2.50%)  1
Small intestinal obstruction   2/40 (5.00%)  2
Stomatitis   3/40 (7.50%)  3
Vomiting   5/40 (12.50%)  5
General disorders   
Fatigue   16/40 (40.00%)  20
Feeling cold   2/40 (5.00%)  2
Influenza like illness   1/40 (2.50%)  1
Mucosal inflammation   1/40 (2.50%)  1
Oedema peripheral   1/40 (2.50%)  1
Pain   1/40 (2.50%)  1
Infections and infestations   
Bronchitis   1/40 (2.50%)  1
Nasopharyngitis   1/40 (2.50%)  1
Vaginal infection   1/40 (2.50%)  1
Investigations   
Alanine aminotransferase increased   2/40 (5.00%)  2
Aspartate aminotransferase increased   5/40 (12.50%)  7
Blood alkaline phosphatase increased   2/40 (5.00%)  2
Blood creatine increased   1/40 (2.50%)  1
Blood creatinine increased   1/40 (2.50%)  1
Blood lactate dehydrogenase increased   1/40 (2.50%)  1
Blood thyroid stimulating hormone decreased   1/40 (2.50%)  1
Blood thyroid stimulating hormone increased   1/40 (2.50%)  1
Lymphocyte count decreased   7/40 (17.50%)  11
Neutrophil count decreased   1/40 (2.50%)  1
Platelet count decreased   2/40 (5.00%)  4
Urine analysis abnormal   1/40 (2.50%)  1
Urine protein/creatinine ratio increased   1/40 (2.50%)  1
Weight decreased   1/40 (2.50%)  1
White blood cell count decreased   5/40 (12.50%)  8
Metabolism and nutrition disorders   
Decreased appetite   2/40 (5.00%)  2
Hyperalbuminaemia   1/40 (2.50%)  1
Hyperglycaemia   1/40 (2.50%)  1
Hyperphosphataemia   2/40 (5.00%)  2
Hyperuricaemia   1/40 (2.50%)  1
Hyponatraemia   1/40 (2.50%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia   9/40 (22.50%)  11
Back pain   1/40 (2.50%)  1
Joint stiffness   1/40 (2.50%)  1
Muscle spasms   3/40 (7.50%)  3
Musculoskeletal discomfort   1/40 (2.50%)  1
Musculoskeletal pain   5/40 (12.50%)  5
Musculoskeletal stiffness   1/40 (2.50%)  1
Myalgia   1/40 (2.50%)  1
Nervous system disorders   
Encephalopathy   1/40 (2.50%)  1
Headache   2/40 (5.00%)  2
Hypoaesthesia   1/40 (2.50%)  1
Neuropathy peripheral   2/40 (5.00%)  2
Taste disorder   2/40 (5.00%)  2
Psychiatric disorders   
Anxiety   1/40 (2.50%)  1
Renal and urinary disorders   
Proteinuria   2/40 (5.00%)  2
Respiratory, thoracic and mediastinal disorders   
Cough   2/40 (5.00%)  3
Dysphonia   4/40 (10.00%)  4
Dyspnoea   2/40 (5.00%)  2
Epistaxis   3/40 (7.50%)  5
Nasal dryness   1/40 (2.50%)  1
Rhinorrhoea   2/40 (5.00%)  2
Skin and subcutaneous tissue disorders   
Blister   1/40 (2.50%)  1
Dermatitis   1/40 (2.50%)  1
Dry skin   2/40 (5.00%)  2
Dyshidrotic eczema   1/40 (2.50%)  1
Nail discolouration   1/40 (2.50%)  1
Onychoclasis   1/40 (2.50%)  1
Pruritus   3/40 (7.50%)  3
Pruritus generalised   1/40 (2.50%)  1
Rash   5/40 (12.50%)  5
Vascular disorders   
Hypertension   14/40 (35.00%)  22
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Katy Wang, Statistician, M.A.
Organization: Roswell Park Comprehensive Cancer Institute
Phone: 7168451300 ext 6269
EMail: katy.wang@roswellpark.org
Layout table for additonal information
Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT02853318    
Other Study ID Numbers: I 270715
NCI-2016-00534 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 270715 ( Other Identifier: Roswell Park Cancer Institute )
First Submitted: July 29, 2016
First Posted: August 2, 2016
Results First Submitted: August 28, 2020
Results First Posted: November 6, 2020
Last Update Posted: October 6, 2021