Clinical trial NCT06236360: Metastatic Melanoma Patients on Immunotherapy With Nutritive Intervention Based on Mediterranean Diet
Official title: The Effect of Individualized Nutritive Intervention Based on the Mediterranean Diet on the Changes in the Gut Microbiome, Quality of Life, and Radiological and Biochemical Response to Immunotherapy in Metastatic Melanoma Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Melanoma Stage Iv
Metastatic Melanoma
Keywords: melanoma
immunotherapy
metastasis
mediterranean diet
Lead sponsor: University Hospital Rijeka
Sponsor class: OTHER
First posted: 2024-02-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This research will study the effect of Mediterranean diet intervention in patients undergoing immunotherapy treatment for metastatic melanoma and its relationship with gut microbiome and quality of life. One group of patients will continue with their regular diet, while the other will receive dietary tele-intervention with trained nutritionist during the 12-week period. Gut microbiome, quality of life questionnaires, blood parameters and radiological examination will be evaluated before and 12-weeks after the start of the intervention.

Detailed description: Metastatic melanoma is a malignant tumor of melanocyte origin that has spread to other organs. The basis of treatment is systemic therapy, most commonly anti-programmed death-1 (PD-1) and anti- cytotoxic T-lymphocyte-associated protein 4 (CTLA- 4) immunotherapy, although for some patients, thyrosine kinase inhibition is also a treatment option. Survival of metastatic melanoma patients has been significantly extended over the last decade, and the use of immunotherapy has led to a median overall survival of 72 months and a response rate of up to 60%. However, not all cancer patients respond equally to immunotherapy, and the variation in response may be attributed to the individual's microbiome, which is heavily influenced by dietary habits. Over 2/3 of patients will progress during the 6.5 years of follow-up and currently there is a limited number prognostic and predictive parameters to assess the response to immunotherapy. However, understanding and manipulating the microbiome through dietary interventions offers a potential avenue for enhancing immunotherapy outcomes in cancer patients and, consequently, may serve as a complementary therapeutic strategy. Due to previous data, as well as investigators' previous publication on the importance of gut microbiome as a co-denominator for immunotherapy response, and aiming towards constructing a protocol on dietary intervention for enhancing immunotherapy response in metastatic melanoma patients, the investigators evaluated a systematic search for the data showing association with an improved immunotherapy response.

A diet with moderately elevated sodium use (2.3-4 g daily), diet rich in fiber (20-25 g daily), fruits and vegetables (≥5 servings daily), vitamin D, 23 omega-3 fatty acids and whole grains (≥3 servings daily) has been associated with a more diverse and beneficial microbiome, which in turn promotes the production of short-chain fatty acids (SCFA). All the listed foods belong to the Mediterranean diet (MD), which is based on fresh fruits and vegetables, legumes, olive oil, and unrefined fiber. MD also includes a lower intake of meat, eggs, processed foods, sugars, and saturated fatty acids, which may all lead to a less diverse and potentially less favorable microbiome and health outcomes. Various clinical studies already demonstrated the beneficial effect of MD in non-oncology patients. As for oncology patients, the benefit of the MD in reducing the incidence of cancer has been known for many years, especially for breast cancer patients. Furthermore, a published cohort study with 52 patients receiving immune checkpoint blockade (ICB) treatment for various solid tumors revealed that higher fecal SCFA concentrations were associated with longer progression-free survival. Another cohort study comprising patients with advanced melanoma in the UK and the Netherlands, demonstrated that a stronger adherence to the MD principles was linked to a higher likelihood of responding positively to ICB treatment. However, there is a scarcity of randomized trials evaluating the effect of the nutritional intervention based on the MD in cancer patients undergoing treatment. As far as the investigators are aware, there are no current clinical trials applying a nutritional intervention based on the MD in patients with metastatic melanoma; however, there is an ongoing randomized DIET study - NCT04645680 (with expected ending in 2024), aiming to evaluate effectiveness of fiber-enriched diet within the melanoma setting. The potential effect of the MD based nutritional intervention could result in a greater benefit compared to trials focusing only on one nutrient. Considering the issues learned from COVID-19 pandemic, the main goal of the trial is to determine the effectiveness and applicability of a remote personalized nutritional intervention based on the MD to increase the intake of micronutrients (flavones, anthocyanins, omega-3 fatty acids, vitamin D and fiber) previously associated with a positive response to immunotherapy.

Eligibility criteria: Inclusion Criteria:

* age ≥18 years
* pathophysiologically confirmed cutaneous melanoma stage IV or inoperable stage IIIC,
* radiologically measurable disease on computerized tomography (CT) or positron emission tomography (PET)/CT,
* The multidisciplinary team recommended initiation of treatment with dual immunotherapy with anti-PD-1 + anti-CTLA4 immunotherapy
* written informed consent prior to participation
* willingness to monitor and adjust the dietary regimen if necessary
* Eastern Cooperative Oncology Group (ECOG) status 0-1.

Exclusion Criteria:

* lifetime history of psychiatric disorders
* active brain metastases
* active autoimmune disease
* systemic use of equal or more than 10 mg of prednisone or an appropriate corticosteroid equivalent during screening
* exposure to antibiotics and probiotics or other supplements that can affect the study outcome during screening within the last 3 weeks,
* uncontrolled diabetes
* history of clinically significant drug or alcohol abuse within the last 6 months
* specific dietary habits that are not inclined or able to change or the existence of food allergy or intolerance to certain food
* inability or refusal to participate in all research procedures

Primary outcomes:
measure: Change in the level of ingested flavones
timeFrame: From enrollment to the end of treatment at 12 weeks
measure: Change in the level of ingested anthocyanins
timeFrame: From enrollment to the end of treatment at 12 weeks
measure: Change in the level of ingested omega-3 fatty acids
timeFrame: From enrollment to the end of treatment at 12 weeks
measure: Change in the level of ingested vitamin D
timeFrame: From enrollment to the end of treatment at 12 weeks
measure: Change in the level of ingested fibre
timeFrame: From enrollment to the end of treatment at 12 weeks
Secondary outcomes:
measure: A change in radiological response rate (PET/CT or CT)
timeFrame: From enrollment to the end of treatment at 12 weeks
measure: A change in gut microbiome strains associated with an improved response to immunotherapy
timeFrame: From enrollment to the end of treatment at 12 weeks
measure: A change in the quality of life assessed by EORTC QLQ C15-PAL
timeFrame: From enrollment to the end of treatment at 12 weeks
measure: A change of biochemical biomarkers of melanoma (S100 and LDH)
timeFrame: From enrollment to the end of treatment at 12 weeks
Other outcomes:
measure: A change of concentration of microbiome associated with a good immune response
timeFrame: From enrollment to the end of treatment at 12 weeks
measure: A correlation between microbiome associated with a good immune response and response
timeFrame: From enrollment to the end of treatment at 12 weeks
measure: A correlation between microbiome associated with a good immune response and less adverse effects
timeFrame: From enrollment to the end of treatment at 12 weeks
Locations:
city: Zagreb
country: Croatia
facility: University Hospital Zagreb-Rebro
state: Grad Zagreb
Study officials:
affiliation: CHC Zagreb
name: Davorin Herceg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: