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Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03274661
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : September 20, 2019
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Miami Cancer Institute
Information provided by (Responsible Party):
Baptist Health South Florida

Tracking Information
First Submitted Date  ICMJE September 5, 2017
First Posted Date  ICMJE September 7, 2017
Last Update Posted Date September 20, 2019
Actual Study Start Date  ICMJE November 2, 2017
Estimated Primary Completion Date March 15, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 5, 2017)
immune-related objective response rate [ Time Frame: every 2 cycles (3 weeks cycles); that is before every third dose of pembrolizumab ]
Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2017)
20-week immune-related progression-free survival rate [ Time Frame: 20-week ]
Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors
Official Title  ICMJE Evaluating Immune Checkpoint Inhibition In Solid Tumor Patients With Homologous Recombination Repair Deficiency
Brief Summary Phase II trial in which patients with metastatic solid tumors experiencing progression after first line standard chemotherapy or for which there is no standard chemotherapy, and for which pembrolizumab does not have an FDA or compendia listing approved indication, will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.
Detailed Description

Patients with metastatic or recurrent solid malignancy who have progressed on first line standard of care treatment or for which defined standard of care does not exist or is not readily available are eligible to participate on this trial. Patients for which pembrolizumab has an FDA approved indication and for whom pembrolizumab is covered by their insurance should receive standard commercial pembrolizumab and will not be eligible for this trial.

The primary objective of this trial is to evaluate the Immune-Related Objective Response Rate (IR-ORR) achieved with pembrolizumab in patients with Fanconi Anemia Repair Pathway functionally competent and functionally deficient tumors.

Trial treatment should be administered on Day 1 of each cycle after all procedures/assessments have been completed. Trial treatment may be administered up to 3 days before or after the scheduled Day 1 of each cycle due to administrative reasons.

All trial treatments will be administered on an outpatient basis.

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Target infusion timing is 30 minutes.

Expansion Cohort:

Ten (10) additional subjects with the diagnosis of metastatic or recurrent endometrial carcinoma will be enrolled in the trial at the conclusion of regular enrollment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Eligible participants will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor, Adult
Intervention  ICMJE Drug: Pembrolizumab 200 mg Q3W
Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle
Other Name: Pembrolizumab 200 mg
Study Arms  ICMJE Experimental: Pembrolizumab 200 mg Q3W
Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle
Intervention: Drug: Pembrolizumab 200 mg Q3W
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: September 5, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 15, 2026
Estimated Primary Completion Date March 15, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have measurable disease based on RECIST 1.1.
  • Be willing to provide consent for retrieval of archival tumor material tissue from a previously obtained core or excisional biopsy of a tumor lesion.
  • Have a tumor presentation at screening for which pembrolizumab does not have an FDA approved indication for commercial use.
  • Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.
  • Demonstrate adequate organ function
  • 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.

Expansion cohort - additional criteria

  1. Diagnosis of Endometrial Carcinoma or Sarcoma which is metastatic and has failed standard treatment or is recurrent, or for which standard chemotherapy is contraindicated or refused by patient.
  2. Sufficient tissue is available for correlative studies
  3. MSI studies have been performed, either by immunohistochemistry or next generation sequencing and results show that patient is MS low or stable.

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 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 a known history of active Bacillus Tuberculosis
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable. 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).
  • Has immunohistochemically proven mismatch repair deficient cancer
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Evidence of interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • 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 or father 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).
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: John P Diaz, MD 786-596-2000 JohnPD@baptisthealth.net
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03274661
Other Study ID Numbers  ICMJE MK-3475-663
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 Baptist Health South Florida
Study Sponsor  ICMJE Baptist Health South Florida
Collaborators  ICMJE
  • Merck Sharp & Dohme Corp.
  • Miami Cancer Institute
Investigators  ICMJE
Principal Investigator: John P Diaz, MD Miami Cancer Institute at Baptist Health, Inc.
PRS Account Baptist Health South Florida
Verification Date September 2019

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