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

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ClinicalTrials.gov Identifier: NCT02834975
Recruitment Status : Recruiting
First Posted : July 15, 2016
Last Update Posted : July 8, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Marilyn Huang, University of Miami

Tracking Information
First Submitted Date  ICMJE July 13, 2016
First Posted Date  ICMJE July 15, 2016
Last Update Posted Date July 8, 2019
Actual Study Start Date  ICMJE December 22, 2016
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2019)
Pathologic Objective Response Rate (pORR) in Participants Receiving Protocol Therapy [ Time Frame: up to 48 months ]
Measure of pathologic response
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2016)
Pathologic Objective Response Rate (pORR) in Participants Receiving Protocol Therapy [ Time Frame: up to 48 months ]
Rate of pathologic objective response rate (pORR) in participants receiving protocol therapy. PORR is defined as complete response + partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
Change History Complete list of historical versions of study NCT02834975 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2016)
  • Progression-Free Survival (PFS) Rate in Participants Receiving Protocol Therapy [ Time Frame: Up to 48 months ]
    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.
  • To confirm safety and tolerability of combination therapy [ Time Frame: Up to 48 Months ]
    Rate of toxicity in participants receiving protocol therapy to confirm the safety and tolerability.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2016)
  • Progression-Free Survival (PFS) Rate in Participants Receiving Protocol Therapy [ Time Frame: Up to 48 months ]
    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.
  • Rate of Toxicity in Participants Receiving Protocol Therapy [ Time Frame: Up to 48 Months ]
    Rate of toxicity in participants receiving protocol therapy to confirm the safety and tolerability.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab, Paclitaxel, and Carboplatin in Patients With Advanced Stage Epithelial Ovarian Cancer (EOC).
Official Title  ICMJE 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
Brief Summary 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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Fallopian Tube Carcinoma
  • Peritoneal Carcinoma
  • Epithelial Ovarian Cancer
Intervention  ICMJE
  • Drug: Pembrolizumab
    Pembrolizumab on Day 1, every 21 days per protocol.
    Other Names:
    • Keytruda
    • MK-3475
  • Drug: Paclitaxel
    Paclitaxel on Day 1, every 21 days per protocol.
    Other Name: Taxol
  • Drug: Carboplatin
    Carboplatin every 21 days per protocol.
Study Arms  ICMJE Experimental: Pembrolizumab, Paclitaxel + Carboplatin
- Neoadjuvant chemotherapy (NACT) will be administered with pembrolizumab, paclitaxel, and carboplatin, on day 1 every 21 days.
Interventions:
  • Drug: Pembrolizumab
  • Drug: Paclitaxel
  • Drug: Carboplatin
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 13, 2016)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02834975
Other Study ID Numbers  ICMJE 20160477
Has Data Monitoring Committee Yes
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
Plan to Share IPD: No
Responsible Party Marilyn Huang, University of Miami
Study Sponsor  ICMJE Marilyn Huang
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Marilyn Huang, MD University of Miami
PRS Account University of Miami
Verification Date July 2019

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