Clinical Trials /

Pembrolizumab, Paclitaxel, and Carboplatin in Patients With Advanced Stage Epithelial Ovarian Cancer (EOC).

NCT02834975

Description:

The investigators hypothesize that tumor cell killing by cytotoxic chemotherapy exposes the immune system to high levels of tumor antigens.The combination of Paclitaxel/Carboplatin and Pembrolizumab may result in deeper and more durable responses compared with standard chemotherapy alone.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab, Paclitaxel, and Carboplatin in Patients With Advanced Stage Epithelial Ovarian Cancer (EOC).
  • Official Title: Phase II Single Arm Study of Combination Pembrolizumab, Paclitaxel, and Carboplatin in Patients With Advanced Stage Ovarian, Fallopian Tube, or Peritoneal Carcinoma Receiving Neoadjuvant Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 20160477
  • NCT ID: NCT02834975

Conditions

  • Fallopian Tube Carcinoma
  • Peritoneal Carcinoma
  • Epithelial Ovarian Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, MK-3475Pembrolizumab, Paclitaxel + Carboplatin
PaclitaxelTaxolPembrolizumab, Paclitaxel + Carboplatin
CarboplatinPembrolizumab, Paclitaxel + Carboplatin

Purpose

The investigators hypothesize that tumor cell killing by cytotoxic chemotherapy exposes the immune system to high levels of tumor antigens.The combination of Paclitaxel/Carboplatin and Pembrolizumab may result in deeper and more durable responses compared with standard chemotherapy alone.

Detailed Description

      This is a single arm, open-label, phase II study to assess pathologic objective response rate
      (complete response + partial response) in patients treated with pembrolizumab, paclitaxel and
      carboplatin for advanced stage III or IV Ovarian, Fallopian Tube, or Peritoneal Carcinoma
      (EOC).

      Eligible patients will undergo tissue biopsies to confirm diagnosis, followed by 3 to 4
      cycles of neoadjuvant chemotherapy (NACT).
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab, Paclitaxel + CarboplatinExperimental- Neoadjuvant chemotherapy (NACT) will be administered with pembrolizumab, paclitaxel, and carboplatin, on day 1 every 21 days.
  • Pembrolizumab
  • Paclitaxel
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          1. No prior treatment for primary advanced (Stage III or IV) high grade epithelial
             ovarian, primary peritoneal, or fallopian tube carcinoma such as irradiation,
             chemotherapy, hormonal therapy, immunotherapy, investigational therapy, and/or other
             concurrent agents or therapies.

          2. Patients must undergo diagnostic laparoscopy for disease assessment for tissue
             biopsies to confirm diagnosis with planned interval tumor reductive surgery after
             completion of 3-4 cycles of treatment. For those not medically fit to undergo
             laparoscopy, as determined by the Investigator. (interventional radiology) IR-guided
             core biopsies may be used.

          3. Patients must be appropriate candidates for planned neoadjuvant chemotherapy with
             combination carboplatin and paclitaxel given intravenously (IV) every 3 weeks.

          4. Tissue from an archival sample or newly obtained core or excisional biopsy of a tumor
             lesion.

          5. Age ≥ 18 years.

          6. Life expectancy > 3 months.

          7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

          8. Patients must have normal organ and marrow function as defined below:

               -  Hematologic

                    -  Absolute neutrophil count (ANC) ≥1,500 /microliter (mcL).

                    -  Platelets ≥ 100,000 / mcL.

                    -  Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or Erythropoietin
                       (EPO) dependency

               -  Renal

                    -  Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR

                    -  Measured or calculated a creatinine clearance ≥60 mL/min for subject with
                       creatinine levels > 1.5 X institutional ULN (GFR can also be used in place
                       of creatinine or CrCl). Creatinine clearance should be calculated per
                       institutional standard.

               -  Hepatic

                    -  Serum total bilirubin ≤ 1.5 X ULN OR

                    -  Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN

                    -  Aspartate transaminase (AST/SGOT) and Alanine transaminase (ALT/SGPT) ≤ 2.5
                       X ULN OR ≤ 5 X ULN for subjects with liver metastases.

                    -  Albumin > 2.5 mg/dL

               -  Coagulation

                    -  International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 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

                    -  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.

          9. Negative urine or serum pregnancy ≤ 72 hours (i.e. 3 days) prior to receiving the
             first dose of study medication if not surgically sterilized. If the urine test is
             positive or cannot be confirmed as negative, a serum pregnancy test will be required.

         10. Female subjects of childbearing potential (have not been surgically sterilized or have
             not been without menses for > 1 year) should be willing to use 2 methods of birth
             control at the same time or be surgically sterile, or abstain from heterosexual
             activity for the course of the study and at least 120 days after the last study dose.

         11. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Patients who are currently in or have participated in a study of an investigational
             agent or used an investigational device within 4 weeks of the first dose of treatment.

          2. Histology showing mucinous or low grade epithelial ovarian cancer.

          3. Patients who will not be likely to undergo interval tumor reductive surgery either
             secondary to performance status or sites of disease. If at the time of surgery, the
             patient is deemed to be surgically resectable to no gross residual, the patient will
             not be eligible for the study.

          4. Patients with known active central nervous system (CNS) metastases and/or
             carcinomatous meningitis. Patients 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 28 days prior to Study treatment.

          5. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy.

          6. Has received prior therapy with an anti-PD1, anti-PDL1, anti-CD137, 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)
             or anti-PDL2 agent.

          7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          8. 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.

          9. 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 adverse events
             administered more than 4 weeks earlier.

         10. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
             weeks prior to study Day 1 or has not recovered (i.e. ≤ Grade 1 or at baseline) from
             adverse events due to previously administered event.

             Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may
             qualify for this study. If subject received major surgery, they must have recovered
             adequately from the toxicity and/or complications from the intervention prior to
             starting therapy.

         11. Has active autoimmune disease that has required systemic treatment in the past two
             years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

         12. Evidence of interstitial lung disease or active, non-infectious pneumonitis

         13. Known psychiatric or substance abuse disorders that would interfere with cooperation
             with requirements of the study.

         14. Is pregnant or breastfeeding or expecting to conceive 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.

         15. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         16. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

         17. Received live vaccine within 30 days prior to the first dose of study treatment. 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.

         18. Patient has active bacillus tuberculosis (TB).

         19. Patient with known hypersensitivity to pembrolizumab or any of its excipients.

         20. Patient receiving concurrent additional biologic therapy.

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

         22. Any other serious medical or psychiatric illness/condition likely in the judgment of
             the Investigator(s) to interfere or limit compliance with study
             requirements/treatment.

         23. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or
             child who is an investigational site or sponsor staff directly involved with this
             trial, unless prospective institutional review board (IRB) approval (by chair or
             designee) is given, allowing exception to this criterion.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic Objective Response Rate (pORR) in Participants Receiving Protocol Therapy
Time Frame:up to 48 months
Safety Issue:
Description:Measure of pathologic response

Secondary Outcome Measures

Measure:Progression-Free Survival (PFS) Rate in Participants Receiving Protocol Therapy
Time Frame:Up to 48 months
Safety Issue:
Description:Rate of Progression-Free Survival (PFS) in participants receiving protocol therapy. PFS is defined as the length of time from the date of first dose of study treatment until date of disease progression or death due to any cause, whichever comes first.
Measure:To confirm safety and tolerability of combination therapy
Time Frame:Up to 48 Months
Safety Issue:
Description:Rate of toxicity in participants receiving protocol therapy to confirm the safety and tolerability.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Marilyn Huang

Trial Keywords

  • Fallopian Tube Carcinoma
  • Peritoneal Carcinoma
  • Epithelial Ovarian Cancer

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