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

NCT02766582 | Completed Phase 2 Results DMC

• 1 other identifier: Uyar 25680 IIT Merck
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Ovarian Cancer

Keywords

Ovarian; platinum; pembrolizumab; taxane

Outcome Measures

Primary Outcomes (1)

• 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 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 Outcomes (1)

• 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 of enrollment until 18 months from initiation of therapy

Other Outcomes (1)

• PD-L1 Expression in Preserved Tissue Obtained at the Time of Initial Diagnosis for Patients

  At enrollment tissue from cytoreductive surgery will be obtained from pathology blocks.

Study Arms (1)

Chemotherapy combined with pembrolizumab

EXPERIMENTAL

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; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Pembrolizumab DRUG

IV every 21 days at 200 mg

Also known as: Keytruda

Chemotherapy combined with pembrolizumab

Carboplatin DRUG

IV every 21 days

Also known as: Paraplatin

Chemotherapy combined with pembrolizumab

Paclitaxel DRUG

IV infusion (80mg/m2) every 7 days for 6 cycles

Also known as: Taxol, Onxol

Chemotherapy combined with pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• The Cleveland Clinic: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Cleveland Clinic

Cleveland, Ohio, United States

Location

Medical College of Wisconsin and Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (50)

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MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

pembrolizumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: D. Denise Uyar
• Organization: Medical College of Wisconsin

duyar@mcw.edu

414-805-6606

Study Officials

• Denise Uyar, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor; Chief of Gynecologic Oncology

Study Record Dates

• First Submitted: March 10, 2016
• First Posted: May 10, 2016
• Study Start: October 1, 2016
• Primary Completion: May 1, 2022
• Study Completion: December 30, 2023
• Last Updated: February 26, 2024
• Results First Posted: June 22, 2023

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)