Clinical Trials /

Study of Pembrolizumab Plus Chemotherapy in Patients With Advanced Cancer (PembroPlus)

NCT02331251

Description:

The Phase Ib and II cohorts will enroll patients with metistatic solid tumors. Phase II only will enroll the following patients: Patients with metastatic sarcoma to be enrolled in the following 4 arms: pembro plus gemcitabine, pembro plus gemcitabine and docetaxel, pembro plus gemcitabine and vinorelbine, and pembro plus liposomal doxorubicin. Patients with metastatic pancreatic adenocarcinoma to be enrolled in the pembro plus gemcitabine and nab-paclitaxel arm. Patients with extensive-stage small cell lung cancer to be enrolled in the pembro plus irinotecan arm. Patients with ER+ breast cancer to be enrolled in the pembro and vinorelbine arm. Patients with ovarian cancer to be enrolled in the pembroplus liposomal doxorubicin arm. Patients with metastatic TNBC (ER/PR/HER2 negative) to be enrolled in the pembro plus gemcitabine arm.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Pancreatic Adenocarcinoma
  • Sarcoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Pembrolizumab Plus Chemotherapy in Patients With Advanced Cancer (PembroPlus)
  • Official Title: A Phase Ib/II Study of Pembrolizumab Plus Chemotherapy in Patients With Advanced Cancer (PembroPlus)

Clinical Trial IDs

  • ORG STUDY ID: PembroPlus
  • NCT ID: NCT02331251

Conditions

  • Advanced Cancer
  • Breast Cancer
  • Sarcoma
  • Pancreatic Cancer
  • Small Cell Lung Cancer
  • Ovarian

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaArm 1
GemcitabineGemzarArm 1
DocetaxelTaxotereArm 2
Nab-paclitaxelAbraxaneArm 3
VinorelbineNavelbineArm 4
IrinotecanCamptosarArm 5
Liposomal DoxorubicinDoxilArm 6

Purpose

The Phase Ib and II cohorts will enroll patients with metistatic solid tumors. Phase II only will enroll the following patients: Patients with metastatic sarcoma to be enrolled in the following 4 arms: pembro plus gemcitabine, pembro plus gemcitabine and docetaxel, pembro plus gemcitabine and vinorelbine, and pembro plus liposomal doxorubicin. Patients with metastatic pancreatic adenocarcinoma to be enrolled in the pembro plus gemcitabine and nab-paclitaxel arm. Patients with extensive-stage small cell lung cancer to be enrolled in the pembro plus irinotecan arm. Patients with ER+ breast cancer to be enrolled in the pembro and vinorelbine arm. Patients with ovarian cancer to be enrolled in the pembroplus liposomal doxorubicin arm. Patients with metastatic TNBC (ER/PR/HER2 negative) to be enrolled in the pembro plus gemcitabine arm.

Detailed Description

      Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalPembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks Gemcitabine 1000 mg/m2 on day 1 and day 8 every 21 days
  • Pembrolizumab
  • Gemcitabine
Arm 2ExperimentalPembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks Gemcitabine 900 mg/m2 on day 1 and 8 and docetaxel 75 mg/m2 on day 8 every 21 days
  • Pembrolizumab
  • Gemcitabine
  • Docetaxel
Arm 3ExperimentalPembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks Gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on day 1 and day 8 every 21 days
  • Pembrolizumab
  • Gemcitabine
  • Nab-paclitaxel
Arm 4ExperimentalPembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks Gemcitabine 1000 mg/m2 and vinorelbine 25 mg/m2 on day 1 and day 8 every 21 days
  • Pembrolizumab
  • Gemcitabine
  • Vinorelbine
Arm 5ExperimentalPembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks Irinotecan 300 mg/m2 on day 1 every 21 days
  • Pembrolizumab
  • Irinotecan
Arm 6ExperimentalPembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks Liposomal doxorubicin 30 mg/m2 on day 1 every 21 days
  • Pembrolizumab
  • Liposomal Doxorubicin

Eligibility Criteria

        Inclusion Criteria:

        1. Patient at least 18 years old and has definitive histologically or cytologically
        confirmed metastatic solid tumor 2. Patient has one or more metastatic tumors measurable by
        CT scan (or PET/CT, if patient is allergic to CT contrast media) 3. The investigator will
        select the appropriate treatment arm for the patient with the following requirements: (a)
        Patients cannot have had prior progression or intolerance on the single agent chemotherapy
        and then enrolled on an arm with that same single agent chemotherapy plus pembro (b) The
        chemotherapy on the arm selected must be considered standard of care or listed in the NCCN
        guidelines (www.nccn.org) for that cancer type 4. Have recovered from acute toxicities of
        prior treatment:

          1. > 3 weeks must have elapsed since receiving any investigational agent

          2. > 2 weeks must have elapsed since receiving any radiotherapy, or ≥ 3 weeks or 5
             half-lives whichever is shorter for treatment with cytotoxic or biologic agents (≥ 6
             weeks for mitomycin or nitrosoureas). Chronic treatment with non-investigational
             gonadotropin-releasing hormone analogs or other hormonal or supportive care is
             permitted 5. Patient has adequate biological parameters as demonstrated by the
             following blood counts at time of screening: 6. Absolute neutrophil count (ANC) > 1500
             mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 9 g/dL 7. Serum creatinine ≤2.0, total
             bilirubin ≤ 2 mg/dL, AST/ALT ≤ 5 times the upper limit of normal (ULN) range (except:
             for the nab-paclitaxel containing arm, bilirubin ≤ 1.25 times the ULN and for the
             docetaxel containing arm, bilirubin must be within institutional normal limits and
             AST/ALT ≤ 1.5 times the ULN) 8. Thyroid stimulating hormone (TSH) within institutional
             normal limits. If TSH is above the upper limit of normal range, then a free T4 within
             institutional normal limits is acceptable 9. Persistent prior systemic therapy
             non-hematologic AE grade ≥ 2 (except alopecia or correctable electrolyte abnormality
             with supplementation) 10. Patient has a Karnofsky performance status (KPS) ≥ 70 11.
             Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically
             sterile) must be willing to use an acceptable contraceptive method (abstinence, oral
             contraceptive or double barrier method) for the duration of the study and for 4 months
             following the last dose of pembrolizumab and 30 days following the last dose of
             chemotherapy on this trial, and must have a negative urine or serum pregnancy test
             within 2 weeks prior to beginning treatment on this trial Phase II only

               1. Patients must have metastatic sarcoma to be enrolled in the following 4 arms:
                  pembro plus gemcitabine, pembro plus gemcitabine and docetaxel, pembro plus
                  gemcitabine and vinorelbine, and pembro plus liposomal doxorubicin

               2. Patients must have metastatic pancreatic adenocarcinoma to be enrolled in the
                  pembro plus gemcitabine and nab-paclitaxel arm

               3. Patients must have extensive-stage small cell lung cancer to be enrolled in the
                  pembro plus irinotecan arm

        Exclusion Criteria:

          1. Active clinically serious infection > CTCAE (version 4.03) Grade 2.

          2. Serious non-healing wound, ulcer, or bone fracture

          3. Patient has known brain metastases, unless previously treated and well-controlled for
             at least 1 month (defined as clinically stable, no edema, no steroids and stable in 2
             scans at least 4 weeks apart)

          4. Inability to complete informed consent process and adhere to the protocol treatment
             plan and follow-up requirements

          5. Patient has known active infection with HIV, hepatitis B, or hepatitis C (patients are
             NOT required to be tested for the presence of such viruses prior to therapy on this
             protocol)

          6. Requiring daily corticosteroid dose ≥ 10 mg prednisone or equivalent per day

          7. Patient has undergone major surgery, other than diagnostic surgery (e.g., surgery done
             to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to
             Day 1 of treatment in this study

          8. Patient has a history of allergy or hypersensitivity to any of the study drugs or any
             of their excipients, or the patient exhibits any of the events outlined in the
             Contraindication or Special Warnings and Precautions sections of the product or
             comparator SmPC or Prescribing Information

          9. Patient has serious medical risk factors involving any of the major organ systems, or
             serious psychiatric disorders, which could compromise the patient's safety or the
             study data integrity

         10. Patient will be receiving any other anti-cancer therapy during participation in this
             trial

         11. Prior treatment with pembro. Receipt of other PD-1 inhibitors or PD-L1 inhibitors is
             allowed

         12. Active or prior documented autoimmune disease requiring systemic treatment within the
             past 2 years Phase II portion only

        1. Patients with a history of more than one primary cancer, with the exception of:

          1. curatively resected nonmelanomatous skin cancer;

          2. curatively treated cervical carcinoma in-situ; or

          3. other primary solid tumor treated with curative intent and no known active disease
             present and no treatment administered during the 2 years prior to enrollment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the recommended phase 2 dose
Time Frame:3 weeks
Safety Issue:
Description:Objective for phase Ib: Determine the recommended phase 2 dose (RP2D) of chemotherapy in combination with pembrolizumab (pembro) in subjects with advanced cancer.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Western Regional Medical Center

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