Phase II: Pembrolizumab/Carboplatin/Taxol in Epithelial Ovary Cancer

February 21, 2024 updated by: Denise Uyar, Medical College of Wisconsin

Phase II Open Label Nonrandomized Trial of the Anti PD 1 Therapy Pembrolizumab With First Line Platinum Based Chemotherapy Followed by 12 Months Pembrolizumab Monotherapy for Patients With Stage III/IV Epithelial Ovarian Cancer

Phase II single arm, open label, nonrandomized study. The aim of our study is to assess the Progression Free Survival (PFS) in suboptimally cytoreduced epithelial ovarian/ primary peritoneal/ fallopian tube cancer patients treated with the novel combination of carboplatin every 21 days (triweekly) /weekly paclitaxel IV with pembrolizumab IV followed by maintenance pembrolizumab IV.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Utilization of combination standard intravenous chemotherapy with intravenous pembrolizumab (for 6 cycles) in first line treatment of patients with advanced ovarian cancer post surgery with any residual disease. This will be followed by single agent intravenous pembrolizumab (every 3 weeks) for 12 additional cycles.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States
        • Cleveland Clinic
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin and Froedtert Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Have advance stage III/IV epithelial ovarian, fallopian tube or primary peritoneal cancer
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be 18 years of age or older on day of signing informed consent.
  • Suboptimal cytoreductive surgery defined as any residual disease noted per operative report and/or have measurable/macroscopic disease (defined as target and/or non-target lesions) based on RECIST 1.1.
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
  • Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.
  • Demonstrate adequate organ function
  • All screening labs should be performed within 28 days of treatment initiation.
  • 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.
  • 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.

Exclusion Criteria:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device 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.
  • 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: 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 history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has a known additional malignancy within the last 3 years, or 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.
  • 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • 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.
  • Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study. The investigator should consult the Study Chair.
  • 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.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Patients with borderline ovarian tumors, recurrent epithelial ovarian/ primary peritoneal cancer/fallopian tube cancer or non-epithelial ovarian cancer are not eligible.
  • Has received a live vaccine within 30 days of planned start of study therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Chemotherapy combined with pembrolizumab

Single arm study:

Pembrolizumab IV every 21 days (200 mg) Carboplatin IV every 21 days Paclitaxel IV infusion (80 mg/m2) every 7 days for 6 cycles Followed by 12 months pembrolizumab IV every 21 days
Drug: Pembrolizumab
IV every 21 days at 200 mg
Other Names:
  • Keytruda
Drug: Carboplatin
IV every 21 days
Other Names:
  • Paraplatin
Drug: Paclitaxel
IV infusion (80mg/m2) every 7 days for 6 cycles
Other Names:
  • Taxol
  • Onxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) of Combination Platinum Based Therapy With Anti-Programmed Death (PD)-1 Therapy Followed by Maintenance Anti-PD-1 Therapy in Patients With Epithelial Ovarian Cancer (EOC).
Time Frame: measured from date of completion of primary therapy to the date of the first clinical, biochemical or radiologic evidence of disease progression or death due to any cause

Time to progression free survival (PFS) is the period from study entry (first dose of therapy) until disease progression, death or date of last contact.

All patients underwent baseline computed tomographic scans prior to initiation of therapy. The residual disease information was collected from surgical operative reports as well as post operative CT scans. Treatment responses were assessed with CA 125 at each cycle of therapy. CT scans were performed post-operatively prior to initiation of systemic therapy, at the completion of combination platinum, taxane, and pembrolizumab therapy, and at the completion of maintenance pembrolizumab therapy. CT scans were also performed with increasing CA 125 or if clinically indicated per treating physician and assessments were made using response evaluation criteria in solid tumor (RECIST) criteria defined as a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in non-target l
measured from date of completion of primary therapy to the date of the first clinical, biochemical or radiologic evidence of disease progression or death due to any cause

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Monitor Quality of Life During Combination Therapy and Single Agent Maintenance Therapy With Anti-PD-1 Therapy With the Functional Assessment of Cancer Therapy- Ovarian (FACT- O) Surveys at Intervals During Therapy.
Time Frame: Time of enrollment until 18 months from initiation of therapy

Each cycle is 21 days. All participants were asked to complete FACT-O surveys at baseline/ time of enrollment, at 3 months, 6 months and 18 months from initiation of therapy.

FACT-O is a validated 26-item summary score 112 points that captures the FACT-General (FACT-G) QOL dimensions of Physical Well-Being (7 items), Functional Well-Being (7 items), and an Ovarian Cancer Subscale (12 items). FACT-0 is a survey with 39 items self administered survey. Each item is scored on 5 point Likert-type scale. The FACT-0 scoring range is from 0-44. The subscale scoring ranges for FACT-G is 0-108. The higher the total score the better the patient well-being. the outcome measure data represent FACT-G scoring as it is the section that pertains to QOL.

https://www.facit.org/measures/FACT-O
Time of enrollment until 18 months from initiation of therapy

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
PD-L1 Expression in Preserved Tissue Obtained at the Time of Initial Diagnosis for Patients
Time Frame: At enrollment tissue from cytoreductive surgery will be obtained from pathology blocks.
PD-L1 expression in preserved tissue obtained at the time of initial diagnosis for patients with suboptimally cytoreduced ovarian cancer using immunohistochemistry (IHC) of initial tumor samples and correlate with clinical outcomes of response and survival.
At enrollment tissue from cytoreductive surgery will be obtained from pathology blocks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical College of Wisconsin

Collaborators

Merck Sharp & Dohme LLC
The Cleveland Clinic

Investigators

  • Principal Investigator: Denise Uyar, MD, Medical College of Wisconsin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2016

Primary Completion (Actual)

May 1, 2022

Study Completion (Actual)

December 30, 2023

Study Registration Dates

First Submitted

March 10, 2016

First Submitted That Met QC Criteria

May 5, 2016

First Posted (Estimated)

May 10, 2016

Study Record Updates

Last Update Posted (Estimated)

February 26, 2024

Last Update Submitted That Met QC Criteria

February 21, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Uyar 25680 IIT Merck

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Ovarian Cancer

Clinical Trials on Pembrolizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Croatia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe