A Study of Pembrolizumab With Standard Treatment in Patients With Recurrent Platinum-resistant Ovarian Cancer

NCT02608684 | Completed Phase 2 Results DMC

• 1 other identifier: IIT2015-13-Walsh-PemCiGem
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of anti-PD-1 antibody MK-3475 (pembrolizumab) in combination with gemcitabine and cisplatin chemotherapy in women with recurrent platinum-resistant ovarian cancer.

Conditions

Ovarian Cancer

Keywords

immunotherapy; platinum-resistant ovarian cancer; immune checkpoint inhibitors

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Defined as complete or partial response per RECIST 1.1 criteria with assessment every 6 weeks during first 6 cycles of therapy and every 9 weeks thereafter. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Up to 2 years

Secondary Outcomes (6)

• Overall Response Rate by iRECIST

  Up to 2 years

• Progression-free Survival (PFS) at 6 Months and at 12 Months

  6 months and 12 months

• Time to Progression

  Up to 2 years

• Duration of Response

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

Study Arms (1)

Cisplatin+Gemcitabine+Pembrolizumab

EXPERIMENTAL

2 cycles of 750mg gemcitabine and 30mg cisplatin chemotherapy (standard of care) followed by 4 cycles of gemcitabine and cisplatin combined with pembrolizumab in 21-day treatment cycles followed by single-agent pembrolizumab maintenance therapy for up to 2 years of treatment (6 cycles combination treatment + 28 cycles maintenance). Gemcitabine 750 mg/m2 every 3 weeks (Q3W) x 6 cycles IV infusion -Day 1 and Day 8 of each 3 week cycle Standard of care Cisplatin 30 mg/m2 Q3W x 6 cycles IV infusion -Day 1 and Day 8 of each 3 week cycle after gemcitabine Standard of care Pembrolizumab 200 mg Q3W starting with cycle 3 IV infusion -Day 1 of each 3 week cycle after gemcitabine and cisplatin Experimental

Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Pembrolizumab DRUG

Pembrolizumab IV solution

Also known as: Keytruda, MK-3475

Cisplatin+Gemcitabine+Pembrolizumab

Gemcitabine DRUG

Gemcitabine IV solution

Also known as: Gemzar

Cisplatin+Gemcitabine+Pembrolizumab

Cisplatin DRUG

Cisplatin IV solution

Also known as: Platinol

Cisplatin+Gemcitabine+Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/ for the trial.
• Be at least 18 years of age on day of signing informed consent.
• Have histologically confirmed diagnosis of recurrent epithelial ovarian, peritoneal or fallopian tube carcinoma that has progressed within 6 months of prior cytotoxic chemotherapy. Histologic confirmation of the primary tumor by review of the pathology report is required. Patients must have had at least one prior platinum-based chemotherapeutic regimen. Initial treatment may have been administered as an intraperitoneal, intravenous or dose-dense regimen. Progression within 6 months of a non-platinum containing regimen is eligible if the patient is considered platinum-resistant to the last platinum-containing regimen. Patients who have received prior cisplatin and gemcitabine treatment are eligible to participate.
• Have measurable disease based on RECIST 1.1
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (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 test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Patients who have had prior hysterectomy and/or bilateral oophorectomy are not required to have a pregnancy test.
• 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. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.

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 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: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery including (curative or palliative surgery), they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Note: Patients who have hypertension as an adverse event related to prior angiogenesis targeted therapy may be allowed if ≤ Grade 2 and considered by investigator to be well-controlled on anti-hypertensive agents.
• Has a known additional malignancy 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. Subjects 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 trial 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 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• 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.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

pembrolizumab; Gemcitabine; Cisplatin

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)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Bobbie J. Rimel, MD
• Organization: Cedars-Sinai Medical Center

Bobbie.Rimel@cshs.org

310-423-1126

Study Officials

• Bobbie J Rimel, MD

  Cedars-Sinal Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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, Obstetrics and Gynecology

Study Record Dates

• First Submitted: November 12, 2015
• First Posted: November 20, 2015
• Study Start: February 8, 2016
• Primary Completion: May 17, 2019
• Study Completion: March 7, 2022
• Last Updated: March 23, 2022
• Results First Posted: March 17, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)