Fecal Microbiota Transplant (FMT) in Melanoma Patients
|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: NCT03341143|
Recruitment Status : Recruiting
First Posted : November 14, 2017
Last Update Posted : May 6, 2019
|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Drug: Fecal Microbiota Transplant with Pembrolizumab||Phase 2|
This is a phase II Simon two-stage single-center study of concurrent fecal microbiota transplang (FMT) with pembrolizumab in patients with PD-1 resistant/refractory melanoma. The study will be conducted over a 12-week period (and up to 24-weeks in responding patients).
Patient eligibility is based upon prior exposure to PD-1 inhibitor therapy and response at first (or subsequent) restaging scans from week 12 up to week 52. Patients who have received either nivolumab or pembrolizumab are eligible. Patients who have received pembrolizumab/nivolumab in combination with other investigational agent(s) may be eligible at the discretion of the treating investigator. PD-1 refractory disease is defined as progressive disease (PD) at the first (or subsequent) radiographic evaluation while receiving PD-1 inhibitor treatment as assessed by RECIST v1.1 or immune-related RECIST criteria. Other eligibility criteria include absence of CNS disease, presence of disease amenable to biopsy and lack of contra-indications to FMT administration.
Suitable patients will be identified following restaging study documenting disease progression. Patients will undergo a rapid screening evaluation consisting of CNS imaging if clinically suspected, tumor biopsy, and serological/stool studies to confirm suitability for FMT administration. Eligible patients will receive FMT endoscopically (along with intestinal biopsy) (with cycle 1 pembrolizumab +/- 3 days) followed by 3 further cycles of pembrolizumab (cycles 2-4) following which restaging will be performed. Patients with stable and/or responding disease will continue to receive pembrolizumab on study for 4 cycles. Patients with stable and/or responding disease after 8 cycles of pembrolizumab will continue to receive therapy off study till progression.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Feasibility Study of Fecal Microbiota Transplant (FMT) in Advanced Melanoma Patients Not Responding to PD-1 Blockade|
|Actual Study Start Date :||January 10, 2018|
|Estimated Primary Completion Date :||November 30, 2019|
|Estimated Study Completion Date :||November 30, 2021|
Experimental: Fecal Microbiota Transplant (FMT) with Pembrolizumab
The FMT along with an intestinal biopsy will be performed as outpatient by a gastroenterologist. The FMT is infused into the colon by performing a colonoscopy. FMT will be performed on Cycle 1 Day 1 and will take 15 to 30 minutes.
Pembrolizumab, 200mg, through an IV over 30 minutes on Cycle 1 Day 1 (same day as the FMT), and then again on Day 1 of each 21-day cycle for an additional 3 cycles (Cycles 2 - 4).
Drug: Fecal Microbiota Transplant with Pembrolizumab
FMT is a procedure in which fecal matter or stool is collected from a tested donor, mixed with a saline or other solution, strained and infused into the colon by doing a colonoscopy. The FMT consists of introducing normal bacterial flora contained in stool collected from a donor into your small intestine. In this case, the donor is patient with advanced melanoma who has been treated with a PD-1 inhibitor (nivolumab or pembrolizumab) and has been rendered disease-free as a result. The FMT will be performed on Cycle 1 Day 1.
Pembrolizumab, 200mg, through an IV over 30 minutes on Cycle 1 Day 1 (same day as the FMT, and then again on Day 1 of each 21-day cycle for an additional 3 cycles (Cycles 2 - 4).
- Objective Response Rate (ORR) [ Time Frame: 3 years ]Number of patients with patients with objective responses (Complete Response (CR) + Partial Response (PR)) divided by the total number of evaluable patients, per RECIST 1.1.
- Change in T-cells Composition [ Time Frame: 4 years ]Quantitative differences in CD8 + PD1+ T cells (measured by percent of total cells) and MFI (staining intensity) between pre- and post- treatment samples from patients that respond and patients that do not respond (per RECIST 1.1), to study treatment
- Change in Innate/adaptive immune system subsets [ Time Frame: 4 years ]Changes in CD8+ T-cell receptor diversity (quantified/determined by using Immunoseq analyses), CD4 + Foxp3 + T regulatory cells, CD56 + NK cells, CD68+ dendritic cells between pre- and post- treatment samples from patients that respond and patients that do not respond (per RECIST 1.1), to study treatment.
- Function of T-cells [ Time Frame: 4 years ]Functional analyses (measured by percent of total cells) expressing IFNgamma) and MFI (staining intensity) between pre- and post- treatment samples from patients that respond and patients that do not respond (per RECIST 1.1), to study treatment.
- Association of PD-1 response with (common) gut microbiota [ Time Frame: 4 years ]Changes in bacterial abundance (quantified by the operational taxonomic unit (OTU)) which indicates the number of different species present along with the representative proportion of each species in the sample) and bacterial diversity (quantified by alpha diversity which is defined by the Shannon Index and quantifies both the organismal richness of a sample and the evenness of the organisms' abundance distribution), between pre- and post- treatment samples from patients that respond and patients that do not respond (per RECIST 1.1) to study treatment.
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): NCT03341143
|Contact: Diwakar Davar, MDfirstname.lastname@example.org|
|Contact: Amy Rose, RNemail@example.com|
|United States, Pennsylvania|
|UPMC Hillman Cancer Center||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Amy Rose, RN 412-647-8587 firstname.lastname@example.org|
|Principal Investigator:||Diwakar Davar, MD||Univ of Pittsburgh|