Clinical Trials /

Pembrolizumab, Carboplatin, and Paclitaxel in Treating Patients With Stage III-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT02520154

Description:

This phase II trial studies how well pembrolizumab works when given in combination with carboplatin and paclitaxel in treating patients with stage III-IV ovarian, primary peritoneal, or fallopian tube cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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 in combination with carboplatin and paclitaxel may be a better treatment for ovarian, primary peritoneal, or fallopian tube cancer.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab, Carboplatin, and Paclitaxel in Treating Patients With Stage III-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
  • Official Title: Matched Paired Pharmacodynamics and Feasibility Study of Pembrolizumab in Combination With Chemotherapy in Frontline Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2014-0662
  • SECONDARY ID: NCI-2015-01508
  • SECONDARY ID: 2014-0662
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02520154

Conditions

  • Stage III Fallopian Tube Cancer AJCC v7
  • Stage III Ovarian Cancer AJCC v6 and v7
  • Stage III Primary Peritoneal Cancer AJCC v7
  • Stage IIIA Fallopian Tube Cancer AJCC v7
  • Stage IIIA Ovarian Cancer AJCC v6 and v7
  • Stage IIIA Primary Peritoneal Cancer AJCC v7
  • Stage IIIB Fallopian Tube Cancer AJCC v7
  • Stage IIIB Ovarian Cancer AJCC v6 and v7
  • Stage IIIB Primary Peritoneal Cancer AJCC v7
  • Stage IIIC Fallopian Tube Cancer AJCC v7
  • Stage IIIC Ovarian Cancer AJCC v6 and v7
  • Stage IIIC Primary Peritoneal Cancer AJCC v7
  • Stage IV Fallopian Tube Cancer AJCC v6 and v7
  • Stage IV Ovarian Cancer AJCC v6 and v7
  • Stage IV Primary Peritoneal Cancer AJCC v7

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (carboplatin, paclitaxel, and pembrolizumab)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratTreatment (carboplatin, paclitaxel, and pembrolizumab)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (carboplatin, paclitaxel, and pembrolizumab)

Purpose

This phase II trial studies how well pembrolizumab works when given in combination with carboplatin and paclitaxel in treating patients with stage III-IV ovarian, primary peritoneal, or fallopian tube cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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 in combination with carboplatin and paclitaxel may be a better treatment for ovarian, primary peritoneal, or fallopian tube cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate progression-free survival of paclitaxel/carboplatin and pembrolizumab in
      patients with advanced stage, metastatic ovarian cancer undergoing neoadjuvant chemotherapy
      (NACT).

      SECONDARY OBJECTIVES:

      I. To describe the feasibility of combination therapy and maintenance pembrolizumab in this
      population.

      II. To evaluate the safety of combination and maintenance pembrolizumab. III. To report
      overall survival.

      EXPLORATORY OBJECTIVES:

      I. To describe the sequential effects of chemotherapy on immune response and PD-1 expression
      and receptor occupancy.

      II. To evaluate circulating lymphoid populations (subsets). III. To determine tissue PD-L1
      expression and T-cell infiltration.

      OUTLINE:

      NACT: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15, and
      carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 3 cycles in the
      absence of disease progression or unacceptable toxicity. Patients then undergo surgery.

      ADJUVANT THERAPY: Beginning 3-6 weeks after surgery, paclitaxel IV over 1 hour on days 1, 8,
      and 15, patients receive carboplatin IV over 1 hour on day 1, and pembrolizumab IV over 30
      minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease
      progression or unacceptable toxicity.

      MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment
      repeats every 21 days for up to 20 cycles in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up every 12 weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (carboplatin, paclitaxel, and pembrolizumab)ExperimentalNACT: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. ADJUVANT THERAPY: Beginning 3-6 weeks after surgery, paclitaxel IV over 1 hour on days 1, 8, and 15, patients receive carboplatin IV over 1 hour on day 1, and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 20 cycles in the absence of disease progression or unacceptable toxicity.
  • Carboplatin
  • Paclitaxel
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Signed, written informed consent

          -  Histology showing high-grade epithelial non-mucinous ovarian, primary peritoneal, or
             fallopian tube cancer

          -  No more than 4 prior cycles of chemotherapy for primary advanced (stage III or IV)
             epithelial ovarian, primary peritoneal, or fallopian tube cancer

          -  No prior treatment involving irradiation, hormonal therapy, immunotherapy,
             investigational therapy, and/or other concurrent agents or therapies for ovarian
             cancer

          -  A disposition to neoadjuvant chemotherapy with planned interval tumor reductive
             surgery after 4 complete cycles of treatment

          -  Planned dose-dense chemotherapy with combination carboplatin and paclitaxel given
             intravenously

          -  Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
             1.1.

               -  Measurable disease is defined at least one lesion that can be accurately measured
                  in at least one dimension (longest dimension to be recorded); each "target"
                  lesion must be >= 20 mm when measured by conventional techniques, including
                  palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging
                  (MRI), or >= 10 mm when measured by spiral CT

               -  Patients with non-measurable but evaluable solid tumors may be deemed eligible
                  contingent upon principal investigator (PI) review

          -  Peripheral neuropathy grade 0 or 1 by National Cancer Institute (NCI) Common
             Terminology Criteria for Adverse Events (CTCAE) version 4.0

          -  Tissue from an archival tissue sample or fresh tissue obtained from a core or
             excisional biopsy of a tumor lesion

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Absolute neutrophil count (ANC) >= 1,500 /mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin (Hgb) >= 9 g/dL or >= 5.6 mmol/L

          -  Creatinine clearance >= 60 mL/min for subject with creatinine levels > 1.5 x
             institutional upper limit of normal (ULN)

          -  Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total
             bilirubin levels > 1.5 ULN

          -  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

          -  International normalized ratio (INR)/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)

          -  PTT =< 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)

          -  Women of child-bearing potential (intact uterus) should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first 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; 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; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Pre-treatment fresh frozen tissue available for research purposes; this tissue can be
             collected from preoperative laparoscopy, other diagnostic biopsy, or a
             research-specific biopsy

          -  Signed informed consent on protocol LAB02-188

        Exclusion Criteria:

          -  Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device within 4 weeks of the first dose of treatment

          -  Histology showing mucinous or low grade epithelial ovarian carcinoma

          -  History of another primary malignancy except for:

               -  Malignancy treated with curative intent and with no known active disease >= 5
                  years before the first dose of study drug and or low potential risk for
                  recurrence

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of disease e.g., cervical
                  cancer in situ

               -  Concomitant stage 1A/B, grade 1-2 endometrioid endometrial cancer as allowable
                  contemporary tumor

          -  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 study 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 study treatment

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways)

          -  Patients with ovarian cancer not medically fit for diagnostic laparoscopy prior to
             initiation of therapy

          -  Patients with any evidence of severe or uncontrolled systemic disease (e.g. severe
             hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung
             disease], uncontrolled chronic renal disease [glomerulonephritis, nephritic syndrome,
             Fanconi syndrome or renal tubular acidosis]), or current unstable or uncompensated
             respiratory or cardiac conditions, or uncontrolled hypertension blood pressure >=
             140/90, active bleeding diatheses or active infection

          -  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 study
             treatment

          -  Has had a prior monoclonal antibody 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

          -  No active autoimmune disease that has required systemic treatment in past two 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 evidence of interstitial lung disease or active, non-infectious 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 study, interfere with the subject's
             participation for the full duration of the study, 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 study

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the pre-screening or screening visit
             through 120 days after the last dose of study treatment

          -  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 prior to the first dose of study treatment

          -  Patients with tuberculosis

          -  Patients with known hypersensitivity to pembrolizumab or any of its excipients

          -  Patients receiving concurrent additional biologic therapy

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to carboplatin, paclitaxel not responsive to traditional desensitization
             procedures

          -  Patient that is not able to understand or to comply with the study instructions and
             requirements or has a history of non-compliance to the medical regimen
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate
Time Frame:Up to 3 years
Safety Issue:
Description:Tumor response will be tabulated and the rates of residual disease (complete resection, < 1 cm residual disease, and >= 1 cm residual disease), interval response (pathological response rate) and overall response (complete response) will be estimated with 90% confidence intervals, and response rates will be compared with a contemporary control group using Fisher's exact test.

Secondary Outcome Measures

Measure:Proportion of patients able to complete all planned cycles of therapy
Time Frame:Up to 546 days (26 cycles, with each cycle equal to 3 weeks)
Safety Issue:
Description:The percentage of patients unable to complete all planned cycle of therapy will be estimated with a 90% credible interval. The posterior probability that the percent of patients unable to complete all planned cycles of therapy is more than 10% will be reported.
Measure:Incidence of adverse events
Time Frame:Up to 3 years
Safety Issue:
Description:Will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Adverse events will be tabulated by grade and relationship to study drug.
Measure:Overall survival
Time Frame:Up to 3 years
Safety Issue:
Description:Cox proportional hazards regression will be used to model overall survival as a function of biomarker expression.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated