Metastatic MelanomaPhase 1MCGRAWNCT03817125
Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention
A Phase 1 study testing Vancomycin pretreatment, Nivolumab and SER-401 in people with Metastatic Melanoma, run by Parker Institute for Cancer Immunotherapy at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- Vancomycin pretreatment, Nivolumab and SER-401
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 7 sitesUnited States
- Study dates
- 28 Jan 2019to 4 Mar 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must be willing to provide a baseline stool sample.
- 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.
- 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).
- Malignant lymph nodes must be ≥ 15 mm in short axis when assessed by CT scan to be considered pathologically enlarged and measurable.
- Participants must have at least one measurable lesion by RECIST and a separate lesion amenable to biopsy that has not been previously irradiated.
- 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.
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- Participants must be willing to undergo tumor biopsy on treatment.
- 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.
- 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.
Who cannot join
- Participants who require hemodialysis.
- 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.
- Any known, untreated brain metastases. Participants with brain metastases are eligible if these have been treated, and provided:
- 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.
- Neurological symptoms should be absent or returned to baseline.
- Prior checkpoint inhibitor therapy with anti-PD-1 or anti-PD-L1 in the adjuvant setting.
Show all 19Show fewer
- Exception: Participants with stage 3 or 4 cutaneous melanoma status post-resection who have received up to one year of adjuvant anti-PD-1 therapy who have recurred > 6 months after their last dose of anti-PD-1 therapy are eligible.
- Other prior systemic treatment (ie, anticancer chemotherapy, immunotherapy, or investigational agents) for unresectable or metastatic melanoma EXCEPT:
- 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.
- Prior anti-CTLA 4 therapy in the adjuvant setting are allowed if completed at least 12 weeks prior to the first dose of anti-PD-1.
- 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).
- 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.
- Participants with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
- 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.
- History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (ie, bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan.
- History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Has a transplanted organ or has undergone allogeneic bone marrow transplant.
- Has received a live vaccine within 30 days prior to first dose. Participants must not receive live, attended influenza vaccine (eg, FluMist) within 30 days prior to Cycle 1, Day 1 or at any time during the study and 100 days after last dose of nivolumab.
- Has used antibiotics within 30 days prior to randomization or has planned or required need for antibiotic prophylaxis for more than 24 consecutive hours during the course of the study.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
MD Anderson Cancer Center
Houston, Texas, 77030
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Metastatic Melanoma
- Being tested
- Placebo for antibiotic, Vancomycin pretreatment, Nivolumab, Matching Placebo for SER-401, SER-401
- Keywords
- Metastatic Melanoma, anti-PD1, Nivolumab, Microbiome, SER-401
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo for antibioticDrug
Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout.
Vancomycin pretreatmentDrug
Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout.
NivolumabDrug
Also called Opdivo
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.
Matching Placebo for SER-401Drug
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.
SER-401Drug
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 group | Role | What they receive |
|---|---|---|
| SER-401 Matching Placebo/ Nivolumab | Placebo comparator | Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Receives: Drug: Placebo for antibiotic; Drug: Nivolumab; Drug: Matching Placebo for SER-401 |
| SER-401/ Nivolumab | Experimental | 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. Receives: Drug: Vancomycin pretreatment; Drug: Nivolumab; Drug: SER-401 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With Adverse Events (AEs)
Investigators recorded AEs during each participant interaction. Symptoms were evaluated by the Investigator using the CTCAE version 5.0. This system grades AEs on a 1 to 5 scale: Grades 1 and 2 indicate mild to moderate events; Grade 3 denotes severe events; Grades 4 and 5 signify life-threatening or fatal outcomes.
A treatment-emergent adverse event (TEAE) is defined as any event that either occurs after the initiation of study intervention, having been absent at baseline, or, if present at baseline, appears to have worsened in severity or frequency, regardless of its relation to the intervention. Adverse events deemed 'Possibly', 'Probably', or 'Definitely' related to the intervention were labeled as treatment-related adverse events (TRAE).
Measured: Up to 2 years
Secondary outcomes (7)
Mean Change From Baseline in the Number of Newly Appearing Spore-forming Species
Engraftment was defined as the number of spore-forming species detected in SER-401 that were absent in participant baseline samples, and present post-microbiome-treatment, also referred to as newly appearing dose species.
Measured: Up to 2 years
Objective Response Rate (ORR)
Objective Response Rate (ORR) is defined as the proportion of participants who attain a best overall response of complete response (CR; disappearance of all target lesions) or partial response (PR; >=30% decrease in the sum of the longest diameter of target lesions), as determined by RECIST version 1.1. Confirmation of response by a repeat tumor assessment is not required.
Measured: Up to week 52
Disease Control Rate (DCR)
Defined as CR, PR, or stable disease (SD) for ≥ 24 weeks as best response by RECIST v1.1.
Measured: Up to week 52
Progression-free Survival (PFS)
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
Measured: Up to 2 years
Overall Survival (OS)
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).
Measured: Up to 2 years
Duration of Response
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).
Measured: Up to 2 years
Absolute Change in the Percentage of CD8 Cells in Tumor Tissue From Baseline at Cycle 2.
Absolute change in the percentage of CD8 cells in tumor tissue from baseline at Cycle 2.
Measured: At cycle 2 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2019
- Study start28 Jan 2019
- Primary completion4 Mar 2022
- Study completion4 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Parker Institute for Cancer Immunotherapy
- Sponsor type
- University, hospital or other
- Collaborators
- Seres Therapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Parker Institute for Cancer Immunotherapy, Study director, Parker Institute for Cancer Immunotherapy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03817125
- Sponsor's protocol ID
- PICI0014
- Acronym
- MCGRAW
- Status last verified
- Jun 2024
- First submitted
- 18 Jan 2019
- Last updated
- 6 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Alang N, Kelly CR. Weight gain after fecal microbiota transplantation. Open Forum Infect Dis. 2015 Feb 4;2(1):ofv004. doi: 10.1093/ofid/ofv004. eCollection 2015 Jan.
PubMed 26034755Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Ding S, Byrd DR, Cascinelli N, Cochran AJ, Coit DG, Eggermont AM, Johnson T, Kirkwood JM, Leong SP, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sondak VK. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol. 2010 May 10;28(14):2452-9. doi: 10.1200/JCO.2009.27.1627. Epub 2010 Apr 5.
PubMed 20368546Choi HH, Cho YS. Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives. Clin Endosc. 2016 May;49(3):257-65. doi: 10.5946/ce.2015.117. Epub 2016 Mar 9.
PubMed 26956193Dubberke ER, Lee CH, Orenstein R, Khanna S, Hecht G, Gerding DN. Results From a Randomized, Placebo-Controlled Clinical Trial of a RBX2660-A Microbiota-Based Drug for the Prevention of Recurrent Clostridium difficile Infection. Clin Infect Dis. 2018 Sep 28;67(8):1198-1204. doi: 10.1093/cid/ciy259.
PubMed 29617739Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PubMed 19097774Ekwueme DU, Guy GP Jr, Li C, Rim SH, Parelkar P, Chen SC. The health burden and economic costs of cutaneous melanoma mortality by race/ethnicity-United States, 2000 to 2006. J Am Acad Dermatol. 2011 Nov;65(5 Suppl 1):S133-43. doi: 10.1016/j.jaad.2011.04.036.
PubMed 22018062Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2.
PubMed 29097493Hamilton MJ, Weingarden AR, Unno T, Khoruts A, Sadowsky MJ. High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria. Gut Microbes. 2013 Mar-Apr;4(2):125-35. doi: 10.4161/gmic.23571. Epub 2013 Jan 18.
PubMed 23333862Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5.
PubMed 20525992Khanna S, Button JE, Lombardo MJ, Vulic M, Henn MR, Cook DN, Pomerantz RJ, Hohmann EL. Reply to Lagier et al. J Infect Dis. 2017 Jan 1;215(1):162-164. doi: 10.1093/infdis/jiw490. Epub 2016 Oct 20. No abstract available.
PubMed 28077592Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Jul 2;373(1):23-34. doi: 10.1056/NEJMoa1504030. Epub 2015 May 31.
PubMed 26027431Lee CH, Steiner T, Petrof EO, Smieja M, Roscoe D, Nematallah A, Weese JS, Collins S, Moayyedi P, Crowther M, Ropeleski MJ, Jayaratne P, Higgins D, Li Y, Rau NV, Kim PT. Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA. 2016 Jan 12;315(2):142-9. doi: 10.1001/jama.2015.18098.
PubMed 26757463Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016 Dec 15;375(24):2369-2379. doi: 10.1056/NEJMra1600266. No abstract available.
PubMed 27974040Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018 Jan 5;359(6371):104-108. doi: 10.1126/science.aao3290.
PubMed 29302014McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994. doi: 10.1093/cid/ciy149.
PubMed 29562266
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03817125
- Acronym / sponsor ID
- MCGRAW / PICI0014
- Conditions
- Metastatic Melanoma
- Keywords
- Metastatic Melanoma, anti-PD1, Nivolumab, Microbiome, SER-401
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Parker Institute for Cancer ImmunotherapyUniversity, hospital or other
- Collaborators
- Seres Therapeutics, Inc.
- Study start
- 28 Jan 2019 (actual)
- Primary completion
- 4 Mar 2022 (actual)
- Study completion
- 4 Mar 2022 (actual)
- First posted
- 25 Jan 2019 (actual)
- Results
- Posted 6 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SER-401 Matching Placebo/ Nivolumab | Placebo comparator | Drug: Placebo for antibiotic, Drug: Nivolumab, Drug: Matching Placebo for SER-401Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. |
| SER-401/ Nivolumab | Experimental | Drug: Vancomycin pretreatment, Drug: Nivolumab, Drug: SER-401Participants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Participant must be willing to provide a baseline stool sample.
- 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.
- 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).
- Participants must be willing to undergo tumor biopsy on treatment.
- 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.
Key exclusion criteria (19 listed)
- Participants who require hemodialysis.
- 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.
- Any known, untreated brain metastases. Participants with brain metastases are eligible if these have been treated, and provided:
- Prior checkpoint inhibitor therapy with anti-PD-1 or anti-PD-L1 in the adjuvant setting.
- Other prior systemic treatment (ie, anticancer chemotherapy, immunotherapy, or investigational agents) for unresectable or metastatic melanoma EXCEPT:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo for antibioticPlacebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. | Drug | SER-401 Matching Placebo/ Nivolumab |
| Vancomycin pretreatmentVancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. | Drug | SER-401/ Nivolumab |
| NivolumabAlso: OpdivoNivolumab (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. | Drug | SER-401 Matching Placebo/ Nivolumab, SER-401/ Nivolumab |
| Matching Placebo for SER-401Administered 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 Matching Placebo/ Nivolumab |
| SER-401Administered 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/ Nivolumab |
Primary outcome
Percentage of Patients With Adverse Events (AEs)
Time frame: Up to 2 years
Investigators recorded AEs during each participant interaction. Symptoms were evaluated by the Investigator using the CTCAE version 5.0. This system grades AEs on a 1 to 5 scale: Grades 1 and 2 indicate mild to moderate events; Grade 3 denotes severe events; Grades 4 and 5 signify life-threatening or fatal outcomes. A treatment-emergent adverse event (TEAE) is defined as any event that either occurs after the initiation of study intervention, having been absent at baseline, or, if present at baseline, appears to have worsened in severity or frequency, regardless of its relation to the intervention. Adverse events deemed 'Possibly', 'Probably', or 'Definitely' related to the intervention were labeled as treatment-related adverse events (TRAE).
7 secondary outcomes
Mean Change From Baseline in the Number of Newly Appearing Spore-forming Species
Time frame: Up to 2 years
Objective Response Rate (ORR)
Time frame: Up to week 52
Disease Control Rate (DCR)
Time frame: Up to week 52
Progression-free Survival (PFS)
Time frame: Up to 2 years
Overall Survival (OS)
Time frame: Up to 2 years
Duration of Response
Time frame: Up to 2 years
Absolute 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26034755Alang N, Kelly CR. Weight gain after fecal microbiota transplantation. Open Forum Infect Dis. 2015 Feb 4;2(1):ofv004. doi: 10.1093/ofid/ofv004. eCollection 2015 Jan.
- Background: PubMed 20368546Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Ding S, Byrd DR, Cascinelli N, Cochran AJ, Coit DG, Eggermont AM, Johnson T, Kirkwood JM, Leong SP, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sondak VK. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol. 2010 May 10;28(14):2452-9. doi: 10.1200/JCO.2009.27.1627. Epub 2010 Apr 5.
- Background: PubMed 26956193Choi HH, Cho YS. Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives. Clin Endosc. 2016 May;49(3):257-65. doi: 10.5946/ce.2015.117. Epub 2016 Mar 9.
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- NCT02437487: SER-109 Versus Placebo to Prevent Recurrent Clostridium Difficile Infection (RCDI)Link provided by the sponsor.
- NCT02530385: Fecal Microbiota Transplant for Obesity and MetabolismLink provided by the sponsor.
- NCT02618187: A Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER- 287 in Subjects With Mild-to-Moderate Ulcerative Colitis PatientsLink provided by the sponsor.
- NCT03341143: Fecal Microbiota Transplant (FMT) in Melanoma PatientsLink provided by the sponsor.
- NCT03353402: Fecal Microbiota Transplantation (FMT) in Metastatic Melanoma Patients Who Failed ImmunotherapyLink provided by the sponsor.
- NCT03637803: MRx0518 and Pembrolizumab Combination StudyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parker Institute for Cancer Immunotherapy study director
Parker Institute for Cancer Immunotherapy
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vancomycin pretreatment, Nivolumab and SER-401 in people with Metastatic Melanoma, run by Parker Institute for Cancer Immunotherapy at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With Adverse Events (AEs) (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03817125, which also lists 32 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2024.