Ipilimumab, Maraviroc and Nivolumab in Advanced Metastatic Colorectal and Pancreatic Cancer the LUMINESCENCE Trial

NCT04721301 | Completed Phase 1 DMC

• 1 other identifier: 2017-003297-13
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The study will be conducted in compliance with Good Clinical Practices (ICH-GCP) and the Declaration of Helsinki, and in accordance with applicable legal and regulatory requirements, including archiving of essential documents.

Conditions

Colorectal Cancer Metastatic; Pancreatic Cancer Metastatic

Keywords

microsatellite stable; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Number of participants and severity of treatment-related adverse Events as assessed by CTCAE v4.0

  Safety and tolerability of combined Maraviroc, Ipilimumab and Nivolumab

  up to 11 days

Secondary Outcomes (3)

• Progression Free Survival

  up to 36 months

• Overall Survival

  up to 36 months

• Tissue Response

  up to 3 months

Study Arms (1)

Combination immunotherapy

EXPERIMENTAL

Treatment arm with Nivolumab, Ipilimumab and Maraviroc combination treatment

Combination Product: Nivolumab plus Ipilimumab plus Maraviroc

Interventions

Nivolumab plus Ipilimumab plus Maraviroc COMBINATION_PRODUCT

In the single treatment arm, all patients receive Nivolumab, Ipilimumab and Maraviroc

Combination immunotherapy

Eligibility Criteria

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

You may qualify if:

• written informed consent given, signed and dated
• age ≥ 18 years
• male or female patient with a history of treated metastatic stage IV colorectal or pancreatic cancer with liver metastases of the primary colorectal or pancreatic cancer
• histologically confirmed primary colorectal or pancreatic cancer
• expected survival of at least three months
• Karnofsky performance status \> 70 %
• patients that have received current standard treatment options (or could not receive treatment due to medical reasons, e.g. allergic reactions, contraindications, toxicities etc.) for colorectal cancer (oxaliplatin or irinotecan in combination or alone with 5-FU with or without treatment combinations of cetuximab and/or bevacizumab or panitumumab, trifluridine plus tipiracil) or patients with pancreatic cancer that have received standard treatment options (at least first line therapy, progression or intolerance to oxaliplatin, irinotecan and 5-FU, FOLFIRINOX as first or second line therapy) or platinum containing adjuvant chemotherapy and palliative after first line chemotherapy
• no chemotherapy treatment within the last two weeks (to baseline)
• within the last 2 weeks prior to study day 1 the following laboratory parameters, which should be within the ranges specified:
• Laboratory Parameter Range Absolute neutrophil count (ANC) ≥ 1000/mm3 (≥ 1.0 x 109/L) Platelets ≥ 50.000/mm3 (≥ 80 x 109/L) Creatinine Clearance limit as assessed by GFR \> 360 mL/min/1.73m² ALT and AST \< 3.0 x ULN (w. liver met.) total bilirubin hemoglobin \< 1.5 x ULN \>9 g/dl
• ability to understand character and individual consequences of the clinical trial
• if the patient is female, she must be of non-childbearing potential, or practice highly effective contraception (Pearl Index \<1%, e.g. intrauterine device (IUD)) while receiving study drug and up to 5 months from the last dose of study drug.
• if the patient is male, he must continue contraception for at least 31 weeks (90 days plus the time required for nivolumab to undergo 5 half-lives) after the last dose of investigational drug. In addition, male patients must abstain from sperm donation during this time

You may not qualify if:

• Patients presenting with any of the following criteria will not be included in the trial:
• Patients with severe kidney disorders (GFR of \<30 mL/min/1.73m² and diagnosed kidney disease) or who are on hemodialysis.
• The patient requires concomitant chronic treatment with systemic corticosteroids or any other systemic immunosuppressive agents. Inhaled or topical steroids, and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease (See also Section 7.7)
• Patients taking immunomodulatory medication (e.g. Type 1 interferons).
• Current use of any investigational or non-registered product (drug or vaccine) other than the study treatment
• Patients with a single metastatic lesion without identified concomitant lymph node metastasis (i.e. a patient with the intent to resect the metastasis)
• Patients with metastatic colorectal or pancreatic cancer that have a drastic clinical progression (e.g. from Karnofsky performance 100% to 70%) within the last six weeks before screening cannot participate
• The patient with active autoimmune disease or with a history of autoimmune disease.
• The patient has a family history of congenital or hereditary immunodeficiency.
• The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immunodeficient condition.
• The patient has concurrent chronic severe medical problems (significant heart failure, uncontrolled diabetes, bleeding disorder, interstitial lung disease, etc.), unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
• Patients with untreated known CNS metastases, patients are eligible if CNS metastases are adequately treated and patients are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to trial participation.
• The patient has previous or concomitant malignancies at other sites, except effectively treated carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
• For female patients: the patient is pregnant or lactating.
• History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product

Sponsors & Collaborators

• University Hospital Heidelberg: lead
• German Cancer Research Center: collaborator

Study Sites (1)

University of Heidelberg / NCT

Heidelberg, 69120, Germany

Location

MeSH Terms

Interventions

Nivolumab; Ipilimumab; Maraviroc

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Head of Department Translational Immunotherapy

Model Details: Single Center Phase 1 trial

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: January 22, 2021
• Study Start: January 15, 2017
• Primary Completion: March 15, 2023
• Study Completion: March 15, 2023
• Last Updated: October 17, 2023

Record last verified: 2023-10

Locations

DE (1)