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

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ClinicalTrials.gov Identifier: NCT02608684
Recruitment Status : Active, not recruiting
First Posted : November 20, 2015
Last Update Posted : April 12, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Christine Walsh, Cedars-Sinai Medical Center

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Pembrolizumab Drug: Gemcitabine Drug: Cisplatin Phase 2

Detailed Description:
This is a single-arm, open-label, phase II trial to evaluate the efficacy and safety of anti-PD-1 antibody MK-3475 (pembrolizumab) in combination with standard of care gemcitabine and cisplatin chemotherapy in women with recurrent platinum-resistant ovarian cancer (encompasses ovarian, peritoneal and fallopian tube cancer). Subjects will receive 2 cycles of gemcitabine and cisplatin chemotherapy followed by 4 cycles of gemcitabine and cisplatin combined with pembrolizumab in 21-day treatment cycles. Subjects will continue to receive single-agent pembrolizumab every 21 days as maintenance therapy for up to 2 year until progression or the subject meets withdrawal criteria. Tumor imaging with CT scan will occur at baseline and every 6 weeks (after each second cycle) during chemotherapy treatment and every 9 weeks thereafter. The primary endpoint is efficacy as defined overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST v.1.1). Secondary endpoints for efficacy include progression free survival at 6 and 12 months, time to progression, duration of response and overall survival. Safety and tolerability of the regimen will be determined by assessing the frequency and intensity of adverse events as defined by the Common Terminology Criteria for Adverse Events (CTCAE v.4). Quality of life will be measured using the European Organization for Research and Treatment of Cancer quality of life questionnaire (QLQ-C30).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Pembrolizumab With Cisplatin and Gemcitabine Treatment in Patients With Recurrent Platinum-resistant Ovarian Cancer
Study Start Date : February 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020


Arm Intervention/treatment
Experimental: Cisplatin+Gemcitabine+Pembrolizumab

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
Pembrolizumab IV solution
Other Names:
  • Keytruda
  • MK-3475

Drug: Gemcitabine
Gemcitabine IV solution
Other Name: Gemzar

Drug: Cisplatin
Cisplatin IV solution
Other Name: Platinol




Primary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Up to 2 years ]
    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.


Secondary Outcome Measures :
  1. Overall response rate by iRECIST [ Time Frame: Up to 2 years ]
  2. Progression-free survival (PFS) at 6 months and at 12 months [ Time Frame: 6 months and 12 months ]
    Proportion of patients who have not progressed at 6 and 12 months with progression-free survival calculated from the start of treatment to the date of progression or death from any cause

  3. Time to progression [ Time Frame: Up to 2 years ]
    Calculated in months from the start of treatment to disease progression as defined by RECIST 1.1

  4. Duration of response [ Time Frame: Up to 2 years ]
    Calculated in months as time from documentation of tumor response to disease progression

  5. Overall survival (OS) [ Time Frame: Up to 2 years ]
    Calculated in months from the start of treatment to the date of death from any cause

  6. Frequency and intensity of adverse events (CTCAE v.4) [ Time Frame: Up to 2 years ]
    As measured at each visit, during safety follow up (30 days after discontinuation of treatment) and during follow up (every nine weeks after discontinuation)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

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 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.
  • Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with 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) or positive serum test for HIV as per testing at screening
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected) as per test at screening
  • Has received a live vaccine within 30 days of planned start of study therapy. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02608684


Locations
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United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Christine Walsh, MD Cedars-Sinal Medical Center

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Responsible Party: Christine Walsh, Associate Professor in Residence, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT02608684     History of Changes
Other Study ID Numbers: IIT2015-13-Walsh-PemCiGem
First Posted: November 20, 2015    Key Record Dates
Last Update Posted: April 12, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Christine Walsh, Cedars-Sinai Medical Center:
immunotherapy
platinum-resistant ovarian cancer
immune checkpoint inhibitors

Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Cisplatin
Gemcitabine
Pembrolizumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological