Clinical Trials /

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

NCT03029598

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Carboplatin in Treating Patients With Relapsed or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
  • Official Title: Anti-PD-1 Therapy in Combination With Platinum Chemotherapy for Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Clinical Trial IDs

  • ORG STUDY ID: 9740
  • SECONDARY ID: NCI-2016-01962
  • SECONDARY ID: 9740
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT03029598

Conditions

  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (pembrolizumab, carboplatin)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, carboplatin)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab, carboplatin)ExperimentalPatients 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.
  • Carboplatin
  • Pembrolizumab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame:6 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Response rate (RR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame:6 months
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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.
Measure:PD-L1 expression of primary tumor blocks assessed by immunohistochemical staining
Time Frame:Up to 3.5 years
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:Up to 3.5 years
Safety Issue:
Description: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.
Measure:Best overall response (BOR)
Time Frame:Up to 3.5 years
Safety Issue:
Description:
Measure:Progression-free survival (PFS) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame:Up to 3.5 years
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:University of Washington

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