MelPRO-0322 (CRISTINA Trial) [miCrobiome pRedIctS aPD1 effecTivnes In melaNoma pAtietns] (CRISTINA)

Neoadjuvant Monotherapy With Anti-PD1 Agents in Patients With Resectable Stage IIIB-D Melanoma: Analysis of Novel Biomarkers

The goal of this observational study is to learn about if new biomarkers such as gut microbiota and molecular genetics melanoma features could predict clinical radiological and pathological response to neoadjuvant monotherapy with anti-PD1 agents in patients with resectable stage IIIB-D melanoma. The main questions it aims to answer are:

• radiological and pathological response rate to three doses of antiPD1 agents;
• do radiological and pathological responses correlate with gut microbiota and melanoma molecular genetics features Participants will receive three doses of aPD1 monotherapy as per center routine practice and will undergo regional lymphadenectomy. Before treatment initiation patients will be asked to bring faeces probes and fill out dietary questionnaire as well as just before the surgery.

After sugery adjuvant therapy will be prescribed for 12 month and patients will be followed up according to institutional routine practice for 5 years.

Study Overview

• Status: Recruiting
• Conditions: Melanoma Stage Iii; Melanoma, Skin
• Intervention / Treatment: Diagnostic test: Gut microbiota analysis

Detailed Description

The clinical efficacy of PD1 inhibitors on the 2-year recurrence-free survival of patients with resectable stage III B-D melanoma will be assessed. This indicator will be compared with a historical control group using adjuvant PD1 immunotherapy and targeted therapy. Various factors will be analyzed for their potential impact on immunotherapy effectiveness, including demographics, disease stage and sub-stage, molecular-genetic status of the tumor, composition of the tumor's lymphoid infiltrate, LDH levels, gut microbiome composition, radiological and pathological response to treatment, and the development of immune-mediated adverse events. These findings may help optimize treatment by implementing neoadjuvant therapy for stage III B-D cutaneous melanoma.

• Study Type: Observational
• Enrollment (Estimated): 72

Contacts and Locations

• Study Contact: Name: Igor V Samoylenko, MD; Phone Number: +74993249024; Email: i.samoylenko@ronc.ru
• Study Contact Backup: Name: Angelina O Kuzmenko, MD; Phone Number: +74993249024; Email: angelin.kuzmenko@gmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Recruiting
    • N.N. Blokhin Russian Cancer Research Center, skin tumor department
    • Contact: Angelina O Kuzmenko, MD; Phone Number: +74993249024; Email: angelin.kuzmenko@gmail.com
    • Contact: Igor V Samoylenko, MD, PhD; Phone Number: +7 (499) 444-24-24; Email: i.samoylenko@ronc.ru
    • Principal Investigator: Igor V Samoylenko, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

No specific requurements to study population

Description

Inclusion Criteria:

• Patients aged 18 years and older.
• Performance status according to the Eastern Cooperative Oncology Group (ECOG) of 0-1.
• Patients who have not previously received immunotherapy with anti-PD1, anti-PDL1, or anti-CTLA4 agents.
• Clinical stage III (B-D), i.e., with clinically or radiologically determined metastatic changes in lymph nodes.
• Histologically confirmed involvement of regional lymph nodes.
• Lesions assessable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Exclusion Criteria:

• Patients with melanoma of non-skin localizations.
• Patients with active autoimmune diseases.
• Patients with active infectious diseases.
• Patients with severe concomitant diseases with an ECOG status >1.
• Pregnant or lactating patients.
• Patients requiring the intake of glucocorticoids at a dose greater than 10 mg of prednisone (or equivalent) per day.
• Patients requiring the use of, or having received, systemic antibiotics within 4 weeks prior to the start of the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Group 1; Neoadjuvant

Diagnostic test: Gut microbiota analysis; Patients with resectable stage IIIB-D melanoma will have a lymph node core biopsy to confirm metastatic lesions, following standard procedures. Additionally, a portion of the tumor tissue will be preserved for biomarker analysis. Participants will then be instructed to submit fecal samples and complete a dietary questionnaire before receiving three doses of PD1 monotherapy, in accordance with the center's routine practice, typically spanning 6-10 weeks. Between weeks 10 and 12, a radiological assessment of the response will be conducted. Following this, participants will undergo regional lymphadenectomy, and the pathological response will be evaluated. After surgery, patients will be placed on adjuvant therapy for 12 months as per routine practice of the center . Subsequently, they will be monitored for five years, adhering to the institution's standard follow-up protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year disease-free survival	2-year disease-free survival: time from surgery to disease recurrence (either locoregional or distant) or death from any cause	time from surgery and up to 2 years follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological response rate	Rate of pathological complete response, near-to-pCR, non-pCR/disease progression	from enrollment to surgery (in average up to 20 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
biomarker reproducibility	Gut microbiota isolation and 16S-RNA clusterization	from enrollment to end of the study follow up (in average during 6 months since randomization)

Collaborators and Investigators

• Sponsor: Russian Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: February 23, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: neoadjuvant therapy; gut microbiota; stage IIIB-D resectable melanoma
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma
• Other Study ID Numbers: MelPRO-0322

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD data could be aggregated later with another neoadjuvant study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No