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Trial record 1 of 1 for:    NCT03817125
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Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention (MCGRAW)

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ClinicalTrials.gov Identifier: NCT03817125
Recruitment Status : Recruiting
First Posted : January 25, 2019
Last Update Posted : January 14, 2020
Sponsor:
Collaborator:
Seres Therapeutics, Inc.
Information provided by (Responsible Party):
Parker Institute for Cancer Immunotherapy

Tracking Information
First Submitted Date  ICMJE January 18, 2019
First Posted Date  ICMJE January 25, 2019
Last Update Posted Date January 14, 2020
Actual Study Start Date  ICMJE January 28, 2019
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2019)
Percentage of patients with Adverse Events (AEs) [ Time Frame: Up to 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2019)
  • Determination of the engraftment of SER-401 bacteria in microbiome study intervention group relative to placebo. [ Time Frame: Up to 2 years ]
  • Objective response rate (ORR) at Weeks 24 and 52 [ Time Frame: Up to week 52 ]
    Defined as complete response (CR) or partial response (PR) as best response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 assessment.
  • Disease control rate (DCR) at Weeks 24 and 52 [ Time Frame: Up to week 52 ]
    Defined as CR, PR, or stable disease (SD) for ≥ 24 weeks as best response by RECIST v1.1.
  • Progression-free survival (PFS) Progression free survival [ Time Frame: Up to 2 years ]
    Defined as the time from randomization to date of first documented progression of disease, date of death due to any cause, or date of most recent participant contact that documented progression-free status
  • Overall survival [OS] [ Time Frame: Up to 2 years ]
    Defined as the time from randomization until death or last contact if still alive at the time of final data collection (after completion of anti-PD-1 therapy).
  • Duration of response [ Time Frame: Up to 2 years ]
    Defined as time from date of documented CR or PR to date of first documented progression of disease, date of death due to any cause, or date of most recent participant contact that documented response (ie, scan date).
  • Change in the percentage of CD8 cells in tumor tissue from baseline at Cycle 2. [ Time Frame: At cycle 2 (each cycle is 28 days) ]
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 Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention
Official Title  ICMJE A Multicenter Phase 1b Randomized, Placebo-controlled, Blinded Study to Evaluate the Safety, Tolerability and Efficacy of Microbiome Study Intervention Administration in Combination With Anti-PD-1 Therapy in Adult Patients With Unresectable or Metastatic Melanoma
Brief Summary This study is designed to evaluate the safety and tolerability of treatment with oral microbiome study intervention (SER-401) or matching placebo in combination with anti-programmed cell death 1 (anti-PD-1) therapy (nivolumab) in participants with unresectable or metastatic melanoma. The study also intends to assess clinical outcomes, the impact of microbiome study intervention administration on the microbiome profile, and its association with clinical and immunological outcomes.
Detailed Description This is a Phase 1b, multicenter, randomized, placebo-controlled, blinded study in adult participants with anti-PD-1 therapy naïve, unresectable or metastatic melanoma to evaluate the safety and tolerability of SER-401, or matching placebo in combination with anti-PD-1 therapy (nivolumab). Prior to initiating microbiome study intervention and nivolumab, participants will undergo an antibiotic or antibiotic placebo treatment lead-in to prime the gut microbiome for engraftment of the oral microbiome study intervention. Study intervention groups will be assessed for safety, changes in the microbiome, changes in the percentage of tumoral CD8 T cells, and antitumor activity. Participants must have measurable disease that can be biopsied and consent to baseline and on-treatment biopsies, as well as stool and blood biomarker collection throughout the study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Participants will be randomly assigned in a 2:1 ratio to oral microbiome study intervention or matching placebo. Nivolumab will be administered open-label as standard of care to all groups. Investigators, site personnel, and participants will remain blinded to the assignment of microbiome study intervention throughout the course of the study. Select Sponsor personnel, including but not limited to the Medical Monitor, Clinical Scientists, Biostatistician, and Patient Safety, will be unblinded to treatment assignment for ongoing safety monitoring.
Primary Purpose: Treatment
Condition  ICMJE Metastatic Melanoma
Intervention  ICMJE
  • Drug: Placebo for antibiotic
    Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout.
  • Drug: Vancomycin pretreatment
    Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout.
  • Drug: Nivolumab
    Nivolumab (480 mg) will be administered intravenously (IV) according to institutional guidelines every 4 weeks for up to 12 cycles. A cycle is defined as 4 calendar weeks.
    Other Name: Opdivo
  • Drug: Matching Placebo for SER-401
    Administered once a day for 7 days during the lead-in phase, followed by once a day for 8 weeks during the microbiome/anti-PD-1 treatment phase.
  • Drug: SER-401
    Administered once a day for 7 days during the lead-in phase, followed by once a day for 8 weeks during the microbiome/anti-PD-1 treatment phase.
Study Arms  ICMJE
  • Placebo Comparator: SER-401 Matching Placebo/ Nivolumab
    Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment.
    Interventions:
    • Drug: Placebo for antibiotic
    • Drug: Nivolumab
    • Drug: Matching Placebo for SER-401
  • Experimental: SER-401/ Nivolumab
    Participants will undergo a 4-day lead-in pretreatment with antibiotic (vancomycin) to prime the gut microbiome for engraftment of the oral microbiome study intervention, then SER-401 and nivolumab treatment.
    Interventions:
    • Drug: Vancomycin pretreatment
    • Drug: Nivolumab
    • Drug: SER-401
Publications *

*   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: January 22, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Participant must be willing to provide a baseline stool sample.
  2. Histologically-confirmed Stage IV cutaneous melanoma or Stage III cutaneous, acral or mucosal melanoma that is judged inoperable. Participants with a history of uveal melanoma are not eligible.
  3. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1; ie, defined as at least 1 lesion that can be accurately measured in at least 1 dimension [longest diameter to be recorded] with a minimum size of ≥ 10 mm by computerized tomography [CT] scan or caliper measurement on clinical exam or ≥ 20 mm by chest X-ray).

    1. Malignant lymph nodes must be ≥ 15 mm in short axis when assessed by CT scan to be considered pathologically enlarged and measurable.
    2. Participants must have at least one measurable lesion by RECIST and a separate lesion amenable to biopsy that has not been previously irradiated.

    i. Participants must be willing to undergo a newly-obtained core needle or incisional biopsy at baseline (prior to antibiotic or antibiotic placebo administration). Fine needle aspiration is not acceptable.

  4. Participants must be willing to undergo tumor biopsy on treatment.
  5. Prior adjuvant or neoadjuvant melanoma therapy is permitted if completed at least 6 weeks prior to randomization and all related AEs have either returned to baseline or stabilized.

    1. Prior anti-CTLA-4 therapy in the adjuvant setting is allowed if completed at least 12 weeks prior to the first dose of anti-PD-1.
    2. Prior BRAF-targeted therapy in the neoadjuvant, adjuvant, or metastatic setting is allowed if completed at least 4 weeks prior to the first dose of anti-PD-1.

Exclusion Criteria:

  1. Participants who require hemodialysis.
  2. Participants with a history of another cancer in the last 5 years, except for: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; c) localized prostate cancer not requiring systemic therapy; and c) other primary tumors with no known active disease present that, in the opinion of the Investigator and the Sponsor, will not affect participant outcome in the setting of the current diagnosis.
  3. Any known, untreated brain metastases. Participants with brain metastases are eligible if these have been treated, and provided:

    1. Brain metastases must be stable (image-documented) 4 weeks after completion of treatment for brain metastases and require treatment with less than 10 mg/day prednisone equivalent for at least 2 weeks prior to study intervention administration.
    2. Neurological symptoms should be absent or returned to baseline.
  4. Prior checkpoint inhibitor therapy with anti-PD-1 or anti-PD-L1 in the adjuvant setting.
  5. Prior systemic treatment (ie, anticancer chemotherapy, immunotherapy, or investigational agents) for unresectable or metastatic melanoma.

    a. Prior BRAF-targeted therapy (ie, BRAF or BRAF-MEK) in the metastatic setting is allowed if completed at least 4 weeks prior to the first dose of anti-PD-1.

  6. History of active inflammatory bowel disease (eg, active Crohn's disease or ulcerative colitis) with diarrhea OR major gastrointestinal surgery (not including appendectomy or cholecystectomy) within 3 months of enrollment (ie, signed informed consent for the study), OR any history of total colectomy or bariatric surgery (bariatric surgery which does not disrupt the gastrointestinal lumen, ie, restrictive procedures such as banding, are permitted).
  7. Any diagnosis of autoimmune disease. Participants with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, adrenal insufficiency on replacement dose steroids, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

    a. Participants with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.

  8. Has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study intervention administration or has a contrast allergy requiring premedication with corticosteroids. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  9. Has a transplanted organ or has undergone allogeneic bone marrow transplant.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Recruiting sites have contact information. Please contact the site directly. If there is no contact info, please email mcgraw0014@parkerici.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03817125
Other Study ID Numbers  ICMJE PICI0014
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: Undecided
Responsible Party Parker Institute for Cancer Immunotherapy
Study Sponsor  ICMJE Parker Institute for Cancer Immunotherapy
Collaborators  ICMJE Seres Therapeutics, Inc.
Investigators  ICMJE
Study Director: Ramy Ibrahim, MD Parker Institute for Cancer Immunotherapy
PRS Account Parker Institute for Cancer Immunotherapy
Verification Date January 2020

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