Camu Camu + ICI for Non-Small Cell Lung Cancer

Recruiting at2 trial locations

Overseen by Arielle Elkrief, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must be taking: Anti-PD-1, Platinum-doublet

Must not be taking: Probiotics, Prebiotics, Antibiotics

Disqualifiers: Pregnancy, Severe immunodeficiency, CNS metastases, others

No Placebo Group

Breakthrough Therapy

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses a natural berry supplement to improve gut health in patients with advanced lung cancer and melanoma. These patients often do not respond well to current treatments. The supplement works by increasing beneficial gut bacteria, potentially making cancer treatments more effective. Berries have shown potential against several cancers, including lung cancer and melanoma, by influencing cellular processes and improving gut health.

Do I have to stop taking my current medications for the trial?

The trial requires you to stop taking probiotics and prebiotics at least 2 weeks before starting, and you cannot take them during the trial. Antibiotics should also be stopped 2 weeks before, but if needed during the trial, you can continue. Other medications are not specifically mentioned, so check with the trial team.

What data supports the effectiveness of the drug Camu Camu + ICI for Non-Small Cell Lung Cancer?

Research shows that combining nivolumab and ipilimumab, which are part of the immune checkpoint inhibitors (drugs that help the immune system fight cancer), can improve survival in patients with advanced non-small cell lung cancer compared to traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of Camu Camu and immune checkpoint inhibitors safe for humans?

Immune checkpoint inhibitors like nivolumab and ipilimumab can cause serious side effects, including heart problems and immune-related reactions affecting the skin, liver, and lungs. While these side effects are rare, they should be monitored closely. There is no specific safety data available for Camu Camu in combination with these drugs. ^{6 7 8 9 10}

How is the Camu Camu + ICI treatment different from other drugs for non-small cell lung cancer?

The Camu Camu + ICI treatment is unique because it combines natural ingredients from Camu Camu with immune checkpoint inhibitors (drugs that help the immune system attack cancer cells), which may offer a novel approach compared to traditional chemotherapy or ICI alone. ^{4 11 12 13 14}

Research Team

Arielle Elkrief, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) or melanoma, who are receiving standard immune checkpoint inhibitors (ICIs). Participants must not have had prior anti-PD1 treatments (except specific melanoma patients), be able to swallow capsules, and use effective contraception. Exclusions include recent probiotic/prebiotic use, severe immunodeficiency, active infections requiring systemic therapy, certain autoimmune diseases, and pregnancy.

Inclusion Criteria

I have not received anti-PD1 treatment before, unless I am in cohort 3.

I have been treated with BRAF-targeting drugs before.

I can take care of myself and perform daily activities.

Exclusion Criteria

I am taking medication for an autoimmune disease that is not under control.

I am currently being treated for an infection.

I have only received the flu shot and COVID-19 vaccines, not the nasal spray flu vaccine.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Camu Camu prebiotic in combination with standard-of-care immune checkpoint inhibitors

3 months

Every 21 or 28 days, depending on ICI treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months

Treatment Details

Interventions

• Camu Camu Capsules (Prebiotic)
• Immune Checkpoint Inhibitors (Checkpoint Inhibitor)

Trial Overview The study tests the safety and tolerability of Camu Camu (CC) prebiotic capsules in combination with standard ICIs in treating NSCLC and melanoma. CC may enrich beneficial gut bacteria linked to better ICI response. Patients are grouped based on their disease stage and treatment regimen.

Participant Groups

Group I: Camu-camu (intervention) in addition to standard-of-care ICI Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Dr. Réjean Lapointe

Centre hospitalier de l'Université de Montréal (CHUM)

Chief Medical Officer since 2023

MD from Université de Montréal

Dr. Fabrice Brunet

Centre hospitalier de l'Université de Montréal (CHUM)

Chief Executive Officer since 2015

MD from Université de Montréal

Findings from Research

In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.

The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]

Immune checkpoint inhibitor (ICI) therapy in lung cancer shows a significant survival benefit, with pooled overall survival Cox hazard ratios indicating improved outcomes for patients with higher PD-L1 expression levels, particularly those with PD-L1 ≥ 50% (HR 0.62).

Approximately 10% of patients treated with ICI achieved long-term survival across different treatment lines, although for patients with PD-L1 < 1%, the long-term survival and short-term survival rates did not reach statistical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit. Lin, EP., Hsu, CY., Chiou, JF., et al.[2023]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

In a study of 373 patients from 11 phase I clinical trials, ipilimumab-related grade 3/4 adverse events were more common in patients who responded to treatment, indicating a potential link between therapeutic response and toxicity.

The likelihood of experiencing severe adverse events increased with the number of additional agents used alongside ipilimumab, while longer treatment duration was associated with more low-grade toxicities but not high-grade ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic and predictive factors associated with ipilimumab-related adverse events: a retrospective analysis of 11 NCI-sponsored phase I clinical trials. Chauhan, A., Kabir, T., Wu, J., et al.[2023]

In a study analyzing 2,088 individual case safety reports (ICSRs) related to immune checkpoint inhibitors (ICIs) in Italy, 801 reports documented serious immune-related adverse drug reactions (irADRs), primarily affecting male patients with gastrointestinal and skin toxicities.

Among the ICIs, nivolumab and pembrolizumab were most frequently associated with irADRs, with significant risks identified for pembrolizumab and ipilimumab, highlighting the need for oncologists to recognize and manage these serious side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. Ruggiero, R., Fraenza, F., Scavone, C., et al.[2022]

A meta-analysis of 21 trials involving 11,454 patients found that immune checkpoint inhibitors (ICIs) significantly increase the risk of various immune-related adverse events (irAEs), including colitis, liver enzyme elevation, rash, hypothyroidism, and pneumonitis compared to non-ICI treatments.

While the incidence of fatal irAEs was less than 1%, the study highlights the importance of early recognition and intervention for these adverse events to prevent complications, particularly noting that ipilimumab was linked to a higher risk of certain skin and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients. De Velasco, G., Je, Y., Bossé, D., et al.[2023]

In a study of 128 patients with previously treated non-small cell lung cancer (NSCLC), the combination of nivolumab and docetaxel significantly improved overall survival (OS) to 23.1 months compared to 14.7 months with nivolumab alone.

The combination therapy also resulted in a longer progression-free survival (PFS) of 6.7 months versus 3.1 months for nivolumab alone, although it was associated with higher rates of hematotoxicity and gastrointestinal adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Comparison of Nivolumab versus Nivolumab + Docetaxel for Previously Treated Advanced or Recurrent ICI-Naïve Non-Small Cell Lung Cancer: TORG1630. Taniguchi, Y., Shimokawa, T., Takiguchi, Y., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Impact of clinicopathological features on the efficacy of immune checkpoint inhibitors plus conventional treatment in patients with advanced lung cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Prognostic and predictive factors associated with ipilimumab-related adverse events: a retrospective analysis of 11 NCI-sponsored phase I clinical trials. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Immunotherapy-associated complete heart block in a patient with NSCLC: A case report and literature review. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients. [2023]

10. Spain pubmed.ncbi.nlm.nih.gov

Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

The efficacy and safety of immune checkpoint inhibitor plus chemotherapy in patients with advanced non-small-cell lung cancer: a meta-analysis. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Association of tumour and stroma PD-1, PD-L1, CD3, CD4 and CD8 expression with DCB and OS to nivolumab treatment in NSCLC patients pre-treated with chemotherapy. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

A Randomized Comparison of Nivolumab versus Nivolumab + Docetaxel for Previously Treated Advanced or Recurrent ICI-Naïve Non-Small Cell Lung Cancer: TORG1630. [2023]

14. United States pubmed.ncbi.nlm.nih.gov

Meta-analysis of the Efficacy and Tolerability of Immune Checkpoint Inhibitors Combined With Chemotherapy in First-line Treatment of Small Cell Lung Cancer. [2021]