Clinical trial NCT03772899: Fecal Microbial Transplantation in Combination With Immunotherapy in Melanoma Patients (MIMic)
Official title: Fecal Microbial Transplantation in Combination With Immunotherapy in Melanoma Patients (MIMic)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Melanoma
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2018-12-11
Enrollment: 20
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Immunotherapy has helped many cancer patients in the last 5 years by enhancing a patient's immune system to fight cancer. Anti-Programmed Death (PD-1) immunotherapy drugs such as pembrolizumab and nivolumab remove the breaks from cancer-fighting immune cells and have been effective in treating some melanoma patients. Despite the major breakthrough of immunotherapy in oncology treatment, many patients do not respond to this new class of anti-cancer drugs. Recently, evidence suggests that the microorganisms living in a patient's intestines play a major role in modifying the response to anti-PD-1drugs. Patients who respond to these drugs have a unique and healthy group of microorganisms in their gut. Therefore, positive modification of a cancer patient's gut microorganisms to create a more diverse and healthy microbiome may improve the response to immunotherapy. One method of modifying the microbiome is Fecal Microbial Transplantation (FMT) that is already being successfully used in the clinic to treat non-cancer patients with persistent bacterial infections.

In this study, the investigators will combine FMT with the approved immunotherapy drugs pembrolizumab or nivolumab that are the standard of care for the treatment of advanced melanoma. The purpose of this study is to examine the safety of combining these two therapies in melanoma patients. The investigator will use fecal material from a healthy donor selected via our stringent protocol that is Health Canada approved. In addition to assessing the safety of the combination, the investigator will also study the effect of FMT on the immune system and microbial ecosystem of the gut.


Eligibility criteria: Inclusion Criteria:

* Patients must be 18-years old or older
* Patients must have a confirmed diagnosis of unresectable or metastatic cutaneous melanoma (BRAF wild type or mutant)
* Patients with ECOG performance of 0-2
* Patients must be able to provide written informed consent and understand the infectious risks associated with FMT administration
* Must understand non-infectious risks associated with FMT administration
* Ability to ingest capsules
* Understand that data regarding the long-term safety risk of FMT are lacking
* Patients receiving systemic steroids at physiologic doses are permitted to enroll assuming steroid dose is not above the acceptable threshold (\> 10 mg prednisone daily or equivalent)
* Have measurable disease as per RECIST version 1.1

Exclusion Criteria:

* 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.
* Current or recent \[in the last 90 days\] exposure to high dose oral or IV corticosteroids

  o Patients who require intermittent use of bronchodilators or local steroid injections are not excluded from the study
* Has a diagnosis of immunodeficiency (e.g. HIV, transplantation) or receiving systemic steroid therapy (\>10mg prednisone daily or equivalent) or any other form of immunosuppressive therapy prior to trial treatment
* Ongoing use of antibiotics or previous use of antibiotics in the last two weeks prior to the FMT procedure
* Presence of a chronic intestinal disease (e.g. Celiac, malabsorption, colonic tumor)
* Presence of absolute contra-indications to FMT administration

  * Toxic megacolon
  * Severe dietary allergies (e.g. shellfish, nuts, seafood)
  * Inflammatory bowel disease
  * Anatomic contra-indications to colonoscopy
* Expected to require any other form of systemic or localized anti-neoplastic therapy while on study
* Has a known history of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the patient has undergone potentially curative therapy with no evidence of that disease for five years

  o NOTE: This time requirement also does not apply to patients who underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cancers including cervical cancer, breast cancer, melanoma, or other in situ cancers.
* Active central nervous system (CNS) metastases and/or leptomeningeal involvement
* Patients with leptomeningeal disease (leptomeningeal enhancement on MRI/CT imaging and/or positive CSF cytology)
* Has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents.

  o Patients with vitiligo, type I diabetes, resolved childhood asthma/atopy are exceptions to this rule
* A history of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Has serious concomitant illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, autoimmune diseases, severe obstructive or restrictive pulmonary diseases, active systemic infections, and inflammatory bowel disorders

  o This includes HIV or AIDS-related illness, or active HBV and HCV
* Has an active infection requiring systemic therapy.
* Patient has received a live vaccine within 4 weeks prior to the first dose of treatment

  o 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.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Primary outcomes:
measure: To evaluate the safety of combining Fecal Microbial Transplantation (FMT) using intestinal bacteria existing in the stool of healthy donors with immunotherapy in melanoma patients.
timeFrame: 60 months
Secondary outcomes:
measure: Assess Objective Response Rate
timeFrame: At baseline and every 12 weeks thereafter up to 60 months
measure: To Evaluate the effect(s) combination FMT and immunotherapy has on the gut microbiome
timeFrame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy (2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
measure: Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
timeFrame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
measure: Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
timeFrame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
measure: Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
timeFrame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
measure: Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
timeFrame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
measure: Evaluate the effect(s) combination FMT and immunotherapy has on patient's metabolomics
timeFrame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy (2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Other outcomes:
Locations:
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Montréal
country: Canada
facility: CHUM
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: London Regional Cancer Program
name: John Lenehan, MD
role: PRINCIPAL_INVESTIGATOR
References: