AzTrials
AzTrials

NSCLC Stage IVPhase 1NCT05303493

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

A Phase 1 study testing Camu Camu Capsules (Camu Camu powder encapsulated (500mg each) + ICI in people with NSCLC Stage IV and Melanoma Stage IV, run by Centre hospitalier de l'Université de Montréal (CHUM) at 3 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Camu Camu Capsules (Camu Camu powder encapsulated (500mg each) + ICI
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
3 sitesCanada
Study dates
29 Jun 2022to 15 Jul 2025
Phase
Phase 1
Are there results?
None posted in the registry

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

  • 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;
Show all 11Show fewer
  • 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.

Who cannot join

  • 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;
  • 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;
Show all 22Show fewer
  • 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.
  • 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;
  • 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.
  • Has serious concomitant illnesses, such as: impaired cardiovascular function or clinically significant cardiovascular disease (uncontrolled congestive heart failure requiring treatment (NYHA grade > 3), uncontrolled hypertension, acute myocardial cardiac ischemia or unstable angina < 2 months prior to study entry, and severe cardiac arrhythmia), active inflammatory bowel disorders.
  • Active kidney disease/severe chronic kidney or liver disease or hematological blood test alteration that would preclude safe administration of chemotherapy at the discretion of the sponsor.
  • Has an active infection requiring systemic therapy;
  • Patient has received a live vaccine within 4 weeks prior to the first dose of treatment
  • 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. COVID-19 vaccinations are not live vaccinations and are allowed.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Known life-threatening or severe allergy to CC at the discretion of the sponsor

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

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

    Longueuil, Quebec, J4V 2H2

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

    Montreal, Quebec, H2X 3E4

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

Other trials in Canada

About this study

Official title: Phase I Trial of Camu Camu Prebiotic and Immune Checkpoint Inhibition in Patients With Non-Small Cell Lung Cancer and Melanoma

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.

Read the detailed description

Immune-checkpoint inhibitors (ICI) now represent the backbone therapy for patients with advanced or unresectable non-small cell lung cancer (NSCLC) and metastatic melanoma. However, only a minority of patients obtain durable complete responses.

In patients with advanced NSCLC with a Programmed Death Ligand-1 (PD-L1) expression level below 50%, the standard-of-care is pembrolizumab plus platinum doublet chemotherapy, with overall survival (OS) at 2 years reaching 46%. In patients with advanced melanoma, combination of anti-CTLA-4 (ipilimumab) and anti-PD-1 (nivolumab) is a key standard-of-care option. In a study in patients with advanced melanoma evaluating the combination regimen of nivolumab plus ipilimumab group, OS at 5 years was 52% in the nivolumab plus ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group.

Despite these improvements in outcomes with ICI, these survival and response rates remain suboptimal, and therefore, developing strategies to safely increase ICI efficacy or reverse ICI resistance represents an unmet clinical need. Moreover, there are currently no available options for patients who progress on standard-of-care ICI. Recent pre-clinical studies have demonstrated the role of the gut microbiome in improving ICI efficacy, and therefore, efforts to modulate the gut microbiome is an active area of study. Indeed, two phase I clinical studies evaluating gut microbiome modulation with fecal microbial transplantation (FMT) demonstrated increase in objective response rate compared to historical controls. Moreover, studies in over 8,000 patients (including patients with NSCLC and melanoma) have confirmed the independent and negative role of antibiotics (ATB) in patients receiving ICI, further validating the important role of the gut microbiome.

Therefore, it is clear that modulation of the gut microbiome represents a promising therapeutic strategy in improving ICI efficacy. Other than FMT, 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 preclinical work showed that CC oral supplementation significantly decreased tumor size and had an additive effect in combination with anti-PD-1 in two murine tumor models, MCA-205 (anti-PD-1 sensitive) and E0771 (anti-PD-1 resistant). Flow cytometry and RNA seq analysis of the tumor microenvironment (TME) and T cell depletion showed that CC's anti-tumor effect was dependent on CD8+ T cells. Moreover, CC supplementation was able to transform an anti-PD-1-resistant tumor into an anti-PD-1-sensitive tumor. ATB administration inhibited CC activity, proving that the activity of CC was dependent on the gut microbiome. The 16S rRNA profiling of murine fecal samples showed that CC increased bacterial diversity and enrichment of beneficial bacteria.

CC is available over the counter as a natural prebiotic and has been approved for human clinical trials in obesity (NCT04130321) and HIV (NCT04058392).

Being tested
Camu Camu Capsules (Camu Camu powder encapsulated (500mg each) + ICI
Keywords
CamuCamu, Prebiotics, Immune check points
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Camu Camu Capsules (Camu Camu powder encapsulated (500mg each) + ICIBiological

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

Study groups in NCT05303493
Study groupRoleWhat they receive
Camu-camu (intervention) in addition to standard-of-care ICIExperimentalCamu-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.
Receives: Biological: Camu Camu Capsules (Camu Camu powder encapsulated (500mg each) + ICI

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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)

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

    To evaluate the preliminary activity of CC in combination with single-agent anti-PD-1 in patients with melanoma, and in combination with anti-PD-1 and chemotherapy in patients with advanced NSCLC as measured by ORR (ORR; the rate of complete response plus partial response, as per the iRECIST and RECIST criteria).

    Objective Response Rate (ORR) as defined by the proportion of patients with NSCLC and melanoma whose Best Overall Response (BOR) is either a complete response (CR) or partial response (PR) as assessed by iRECIST, based on RECIST v1.1. BOR is defined as the best response designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy. CR or PR determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2022
  2. Study start29 Jun 2022
  3. Primary completion15 Jul 2025
  4. Study completion15 Jul 2025

Resources

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
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05303493
Sponsor's protocol ID
21.393
Status last verified
Jul 2025
First submitted
22 Sep 2021
Last updated
30 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 37754485

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Camu Camu Capsules (Camu Camu powder encapsulated (500mg each) + ICI in people with NSCLC Stage IV and Melanoma Stage IV, run by Centre hospitalier de l'Université de Montréal (CHUM) at 3 sites in Canada.

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 11 inclusion and 22 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 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. 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. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of treatment-related adverse events (safety and tolerability) in patients with NSCLC and melanoma (time frame: 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)). 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 NCT05303493, which also lists 1 linked publication.

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 30 Jul 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in