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Pembrolizumab and Carboplatin in Treating Patients With Relapsed or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03029598
Recruitment Status : Active, not recruiting
First Posted : January 24, 2017
Last Update Posted : February 17, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Washington

Tracking Information
First Submitted Date  ICMJE January 20, 2017
First Posted Date  ICMJE January 24, 2017
Last Update Posted Date February 17, 2020
Actual Study Start Date  ICMJE March 14, 2017
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
Progression-free survival (PFS) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: 6 months ]
Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% confidence intervals (CIs) at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.
Original Primary Outcome Measures  ICMJE
 (submitted: January 20, 2017)
Progression-free survival (PFS) assessed by RECIST v1.1 [ Time Frame: 6 months ]
Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS and OS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2018)
  • Response rate (RR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: 6 months ]
    The point estimate and the 95% exact CIs will be reported for RR. The comparison with the historical control rate will be conducted by examining whether the 95% confidence internal covers the historical control rate. Additional analyses will be conducted to evaluate in logistic regression models the odds ratio of response rate on predictors such as platinum-free interval, time to progression after previous platinum treatment, number of prior platinum regimens etc
  • Incidence of adverse events evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 3.5 years ]
    The safety population included all patients who received at least one dose of study medication. The descriptions and grading scales found in the revised NCI CTCAE version 4.0 will be utilized for adverse event reporting. The number and the percentage of patients who are removed from the study or altered dose regimen due to adverse effects will be reported.
  • PD-L1 expression of primary tumor blocks assessed by immunohistochemical staining [ Time Frame: Up to 3.5 years ]
    Using logistic regression or Cox regression models, the expression levels of PD1 and the serum antibody levels recognizing p53, BRCA1 and HIF1 alpha will be correlated with the response rate and other efficacy endpoints, adjusted for other clinical and prognostic characteristics. The mutational load (the number of nonsynonymous mutations) of recurrent tumors measured by whole-exome sequencing will be compared to the primary tumors and correlated with the efficacy endpoints. Genomic features that differ between primary tumors and recurrent tumors will be studied for associations with the treatment responses.
  • Overall survival (OS) [ Time Frame: Up to 3.5 years ]
    Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control OS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.
  • Best overall response (BOR) [ Time Frame: Up to 3.5 years ]
  • Progression-free survival (PFS) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 3.5 years ]
    Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.
  • Immune-related best overall response (BOR) assessed using modified Immune-Related Response Criteria (irRC) derived from Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 3.5 years ]
  • Immune-related progression-free survival (PFS) using modified Immune-Related Response Criteria (irRC) derived from Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 3.5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2017)
  • Best overall response (BOR) [ Time Frame: Up to 3.5 years ]
  • Immune-related BOR using modified Immune-Related Response Criteria (irRC) derived from RECIST v1.1 [ Time Frame: Up to 3.5 years ]
  • Immune-related PFS using modified irRC derived from RECIST 1.1 [ Time Frame: Up to 3.5 years ]
  • Incidence of adverse events evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [ Time Frame: Up to 3.5 years ]
    The safety population included all patients who received at least one dose of study medication. The descriptions and grading scales found in the revised NCI CTCAE version 4.0 will be utilized for adverse event reporting. The number and the percentage of patients who are removed from the study or altered dose regimen due to adverse effects will be reported.
  • Overall survival [ Time Frame: Up to 3.5 years ]
    Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS and OS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.
  • PD-L1 expression of primary tumor blocks assessed by immunohistochemical staining [ Time Frame: Up to 3.5 years ]
    Using logistic regression or Cox regression models, the expression levels of PD1 and the serum antibody levels recognizing p53, BRCA1 and HIF1 alpha will be correlated with the response rate and other efficacy endpoints, adjusted for other clinical and prognostic characteristics. The mutational load (the number of nonsynonymous mutations) of recurrent tumors measured by whole-exome sequencing will be compared to the primary tumors and correlated with the efficacy endpoints. Genomic features that differ between primary tumors and recurrent tumors will be studied for associations with the treatm
  • PFS assessed by RECIST v1.1 [ Time Frame: Up to 3.5 years ]
    Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS and OS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.
  • Response rate (RR) assessed by RECIST version (v)1.1 [ Time Frame: 6 months ]
    The point estimate and the 95% exact confidence intervals (CIs) will be reported for RR. The comparison with the historical control rate will be conducted by examining whether the 95% confidence internal covers the historical control rate. Additional analyses will be conducted to evaluate in logistic regression models the odds ratio of response rate on predictors such as platinum-free interval, time to progression after previous platinum treatment, number of prior platinum regimens etc
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab and Carboplatin in Treating Patients With Relapsed or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Official Title  ICMJE Anti-PD-1 Therapy in Combination With Platinum Chemotherapy for Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Brief Summary This phase I/II trial studies how well pembrolizumab and carboplatin work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab and carboplatin may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the clinical response rate of platinum chemotherapy and pembrolizumab (MK-3475) in platinum chemotherapy pretreated ovarian, fallopian tube, and primary peritoneal.

II. To examine whether retreatment with platinum chemotherapy in platinum resistant ovarian, fallopian tube, and primary peritoneal cancers improves progression free survival by concurrent administration of MK-3475.

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of concurrent administration of MK-3475 with platinum chemotherapy in patients with platinum resistant recurrent ovarian, fallopian tube, and primary peritoneal cancers.

II. To determine the relationship between PD-L1 expression and response to the combination of MK-3475 and platinum.

III. To assess the overall survival of patients treated with the combination of MK-3475 and platinum.

EXPLORATORY OBJECTIVES:

I. To explore changes in gene expression of pre and post treatment tumor samples.

II. To explore whether treatment with MK-3475 and platinum alters soluble factors in sera, peripheral immune responses and immune cell profile.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, every 6 months for 1 year, and then every 12 weeks thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
Intervention  ICMJE
  • Drug: Carboplatin
    Given IV
    Other Names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Pembrolizumab
    Given IV
    Other Names:
    • Keytruda
    • Lambrolizumab
    • MK-3475
    • SCH 900475
Study Arms  ICMJE Experimental: Treatment (pembrolizumab, carboplatin)
Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Carboplatin
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 12, 2020)
29
Original Estimated Enrollment  ICMJE
 (submitted: January 20, 2017)
27
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have a diagnosis of ovarian, fallopian tube, or primary peritoneal cancer patients who had a complete response to primary treatment with platinum based chemotherapy, have progressed within 6 months of completing platinum based chemotherapy and have subsequently received at least one, non-platinum-based, therapy
  • Have relapsed, refractory, or progressive disease following last line of treatment
  • Have estimated life expectancy of at least 3 months
  • Be willing and able to provide written informed consent/assent for the trial
  • Have measurable disease with at least 1 unidimensional lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Within 10 days of treatment initiation: Absolute neutrophil count (ANC) >= 1,500/mcL
  • Within 10 days of treatment initiation: Platelets >= 100,000/mcL
  • Within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Within 10 days of treatment initiation: Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
  • Within 10 days of treatment initiation: Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
  • Within 10 days of treatment initiation: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
  • Within 10 days of treatment initiation: Albumin >= 2.5 mg/dL
  • Within 10 days of treatment initiation: International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Within 10 days of treatment initiation: Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year

Exclusion Criteria:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment

    • Short-term administration of systemic steroids (i.e., for allergic reactions or the management of immune related adverse events [irAEs]) is allowed
  • Has a known history of active TB (Bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent

    • Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
    • Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Clinically significant cardiovascular disease
  • Known severe hypersensitivity reactions to monoclonal antibodies or carboplatin >= grade 3, any history of anaphylaxis, or uncontrolled asthma
  • Has received prior therapy with pembrolizumab
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy

    • Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03029598
Other Study ID Numbers  ICMJE 9740
NCI-2016-01962 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9740 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: John Liao Fred Hutch/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP