Camu-Camu Prebiotic and Immune Checkpoint Inhibition in Patients With Non-small Cell Lung Cancer and Melanoma

NCT05303493 | Completed Phase 1 DMC

• 1 other identifier: 21.393
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief Summary

Modulating the gut microbiome to improve response to immune-checkpoint inhibitors is an active area of study. Prebiotic substances (compounds which positively shift the gut microbiome) are a reliable and safe method of gut microbiome modulation. Data suggest that the berry Camu Camu (CC), also known as Myrciaria dubia has prebiotic potential to enrich Akkermansia muciniphila, a bacterium shown to alleviate metabolic disorders and improve ICI efficacy in preclinical models. Our primary objective is to assess the safety and tolerability of CC prebiotic in patients with advanced NSCLC and melanoma in combination with standard-of-care ICI.

Conditions

NSCLC Stage IV; Melanoma Stage IV; Unresectable Melanoma; Advanced Non-Small Cell Lung Cancer

Keywords

CamuCamu; Prebiotics; Immune check points

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-related adverse events (safety and tolerability) in patients with NSCLC and melanoma

  Safety of administration of CamuCamu in the Safety Analysis Dataset. The assessment of safety will be based on the incidence of AEs, SAEs, AEs leading to discontinuation, and deaths in the Safety Analysis dataset. Treatment-related adverse events will be graded according to the NCI CTCAE v5.0. of CC prebiotic in addition to ICI in patients with NSCLC and melanoma on the basis of the following endpoints: * Incidence and severity of AEs, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) * Change from baseline in targeted vital signs * Change from baseline in targeted clinical laboratory test results

  At the end of every cycle (each cycle is 21 or 28 days, depending of the ICI treatment) until disease progression, then, every 3 months thereafter (for up to a total of 2 years)

Secondary Outcomes (1)

• Objective response rate in the NSCLC and melanoma cohort by RECIST criteria.

  At 3 and 6 months, then at 12 months and up to 2 years

Study Arms (1)

Camu-camu (intervention) in addition to standard-of-care ICI

EXPERIMENTAL

Camu-camu (intervention) will be added to standard-of-care ICI in: Cohort 1. For patients with advanced NSCLC, treatment will consist of single-agent pembrolizumab in combination with physician's choice platinum-doublet chemotherapy in combination with CC. Cohort 2. For patients with advanced cutaneous melanoma, treatment will consist of single-agent anti-PD-1 either nivolumab or pembrolizumab at the discretion of the treating physician. Cohort 3. For patients with advanced melanoma receiving standard-of-care ICI (either single-agent anti-PD-1 or combination anti-CTLA-4 plus anti-PD-1) who experience progressive disease (PD), their current regimen will continue unchanged and they will receive CC at 1500 mg for 3 months or until confirmed progression if progression occurs earlier.

Biological: Camu Camu Capsules (Camu Camu powder encapsulated (500mg each) + ICI

Interventions

Camu Camu Capsules (Camu Camu powder encapsulated (500mg each) + ICI BIOLOGICAL

Evaluate the safety and tolerability of CC prebiotic in addition to ICI in patients with NSCLC and melanoma

Camu-camu (intervention) in addition to standard-of-care ICI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, informed consent;
• Age 18 years or older;
• One of the following histological-confirmed diagnoses\*\*
• No prior anti-PD1 treatment (except for patients in cohort 3)
• Evaluable disease as per RECIST 1.1;
• ECOG performance status of 0-2;
• Ability to ingest capsules;
• Patients receiving systemic steroids at physiologic doses are permitted to enroll provided the dose not exceed 10 mg prednisone daily or equivalent;
• Negative pregnancy test for women of child-bearing potential; and
• Highly effective contraception (any method above 97% success rate) for both male and female subjects throughout the study and for at least 60 days after last treatment administration, if the risk of conception exists
• a.Cohort 1: patients with stage IV or unresectable NSCLC (including squamous cell carcinoma) with PD-L1 expression \<50% who are going to be treated with anti-PD-1 in combination with platinum-doublet chemotherapy b.Cohort 2: Patients with untreated stage IV or unresectable cutaneous melanoma, acral or mucosal melanoma who are going to be treated with single-agent anti-PD-1 therapy i. Patients with prior treatment with BRAF-targeting agents (BRAF inhibition +/- MEK inhibition) are permitted to enroll ii. Patients with melanoma of unknown primary are permitted to enroll. Diagnosis of melanoma of unknown primary at the discretion of the treating oncologist and sponsor c.Cohort 3: Patients with stage IV or unresectable cutaneous melanoma, acral or mucosal melanoma already receiving standard-of-care ICI (either single-agent anti-PD-1 or combination anti-CTLA-4 plus anti-PD-1) at the first sign of progression i.Patients with melanoma of unknown primary are permitted to enroll. Diagnosis of melanoma with unknown primary at the discretion of the treating oncologist and PI.

You may not qualify if:

• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment;
• Has a diagnosis of severe immunodeficiency (e.g. transplantation) or receiving systemic steroid therapy (\>10mg prednisone daily or equivalent) or any other form of active immunosuppressive therapy at the discretion of the sponsor;
• a. Patients with well-controlled HIV who are on HAART and have undetectable viral load are permitted to enroll;
• Use of probiotics. Probiotics must be discontinued a minimum of 2 weeks before CC administration and patients are not permitted to take probiotics during the course of immunotherapy treatment;
• Use of natural supplements including prebiotics. Prebiotics must be discontinued a minimum of 2 weeks before CC administration and patients are not permitted to take other prebiotics during the course of immunotherapy treatment;
• Use of antibiotics within 2 weeks of enrollment in the study;
• a. If a patient requires antibiotics during CC treatment, they are permitted to stay on the study.
• Expected to require any other form of systemic anti-neoplastic therapy while on study (radiation therapy is permitted);
• In the last year, has a known history of a malignancy requiring anti-neoplastic treatment.
• a. NOTE: This time requirement 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;
• Symptomatic central nervous system (CNS) metastases
• Leptomeningeal involvement (leptomeningeal enhancement on MRI/CT imaging and/or positive CSF cytology);
• Has an uncontrolled autoimmune disease that requires systemic steroids or immunosuppressive agents;
• a. Patients with vitiligo, type I diabetes, well controlled hypothyroidism due to Hashimoto disease, resolved childhood asthma/atopy are permitted to enroll.
• A history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead

Study Sites (3)

CISSS de la Montérégie-Centre- Hôpital Charles-Le Moyne

Longueuil, Quebec, J4V 2H2, Canada

Location

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (1)

• Pang SA, Elkrief A, Capella MP, Miller WH Jr. Two Cases of Durable and Deep Responses to Immune Checkpoint Inhibition-Refractory Metastatic Melanoma after Addition of Camu Camu Prebiotic. Curr Oncol. 2023 Aug 25;30(9):7852-7859. doi: 10.3390/curroncol30090570.

  PMID: 37754485 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Arielle Elkrief, MD

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cohort 1. For patients with advanced NSCLC, treatment will consist of ICI in combination with CamuCamu. Cohort 2. For patients with advanced cutaneous melanoma, treatment will consist of single-agent anti-PD-1 either nivolumab or pembrolizumab at the discretion of the treating physician in combination with investigational CC capsules Cohort 3. For patients with advanced melanoma receiving standard-of-care ICI who exhibit either an ORR of SD or PD during the first 3 months of ICI initiation, their current regimen will continue unchanged and they will receive Camu C and will be continued for 18 weeks or upon progression.

Study Record Dates

• First Submitted: September 22, 2021
• First Posted: March 31, 2022
• Study Start: June 29, 2022
• Primary Completion: July 15, 2025
• Study Completion: July 15, 2025
• Last Updated: July 30, 2025

Record last verified: 2025-07

Locations

CA (3)