Ipilimumab, Maraviroc and Nivolumab in Advanced Metastatic Colorectal and Pancreatic Cancer the LUMINESCENCE Trial
Primary Purpose
Colorectal Cancer Metastatic, Pancreatic Cancer Metastatic
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Nivolumab plus Ipilimumab plus Maraviroc
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring microsatellite stable, immunotherapy
Eligibility Criteria
Inclusion Criteria:
- 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
- preferentially with metastatic lesion in the liver amenable to biopsy (must have at least one measurable lesion or evaluable disease by CT or MRI per RECIST criteria measured within 56 days prior to trial inclusion)
- 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
Exclusion Criteria:
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
- Known allergy or hypersensitivity to peanuts, soy, soy beans or derivatives of soy or peanuts
- Contra-indication for MRI
- Participation in another clinical trial within three weeks before screening day
- Patient will not be allowed to enroll in this trial more than once.
- Known microsatellite-instability (MSI-H or dMMR) as evidenced by a standard laboratory practice (e.g. PCR or staining or sequencing etc.)
- Prisoners or patients who are involuntarily incarcerated.
- Patients who are compulsorily detained for treatment of either a psychiatric or physical(e.g., infectious disease) illness
Sites / Locations
- University of Heidelberg / NCT
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Combination immunotherapy
Arm Description
Treatment arm with Nivolumab, Ipilimumab and Maraviroc combination treatment
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Progression Free Survival
Progression free survival after initiation of trial medication, time to progression on trial medication, radiologic evaluation based on RECIST and iRECIST criteria
Overall Survival
Overall survival after initiation of trial medication, radiologic evaluation based on RECIST and iRECIST criteria
Tissue Response
Detailed evaluation of in-treatment biopsy compared to pre-treatment biopsies, investigating overt tumor cell death, immune cell activation, immune cell density and general markers of proliferation
Full Information
NCT ID
NCT04721301
First Posted
November 12, 2020
Last Updated
October 16, 2023
Sponsor
University Hospital Heidelberg
Collaborators
German Cancer Research Center
1. Study Identification
Unique Protocol Identification Number
NCT04721301
Brief Title
Ipilimumab, Maraviroc and Nivolumab in Advanced Metastatic Colorectal and Pancreatic Cancer the LUMINESCENCE Trial
Official Title
LUMINESCENCE-001 Ipilimumab, Maraviroc and Nivolumab in Advanced Metastatic Colorectal and Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
January 15, 2017 (Actual)
Primary Completion Date
March 15, 2023 (Actual)
Study Completion Date
March 15, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Heidelberg
Collaborators
German Cancer Research Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
A study to evaluate the safety, tolerability and feasibility of treatment with Maraviroc, nivolumab and ipilimumab in layers of colon and pancreatic cancer patients
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Metastatic, Pancreatic Cancer Metastatic
Keywords
microsatellite stable, immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Single Center Phase 1 trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Combination immunotherapy
Arm Type
Experimental
Arm Description
Treatment arm with Nivolumab, Ipilimumab and Maraviroc combination treatment
Intervention Type
Combination Product
Intervention Name(s)
Nivolumab plus Ipilimumab plus Maraviroc
Intervention Description
In the single treatment arm, all patients receive Nivolumab, Ipilimumab and Maraviroc
Primary Outcome Measure Information:
Title
Number of participants and severity of treatment-related adverse Events as assessed by CTCAE v4.0
Description
Safety and tolerability of combined Maraviroc, Ipilimumab and Nivolumab
Time Frame
up to 11 days
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
Progression free survival after initiation of trial medication, time to progression on trial medication, radiologic evaluation based on RECIST and iRECIST criteria
Time Frame
up to 36 months
Title
Overall Survival
Description
Overall survival after initiation of trial medication, radiologic evaluation based on RECIST and iRECIST criteria
Time Frame
up to 36 months
Title
Tissue Response
Description
Detailed evaluation of in-treatment biopsy compared to pre-treatment biopsies, investigating overt tumor cell death, immune cell activation, immune cell density and general markers of proliferation
Time Frame
up to 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
preferentially with metastatic lesion in the liver amenable to biopsy (must have at least one measurable lesion or evaluable disease by CT or MRI per RECIST criteria measured within 56 days prior to trial inclusion)
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
Exclusion Criteria:
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
Known allergy or hypersensitivity to peanuts, soy, soy beans or derivatives of soy or peanuts
Contra-indication for MRI
Participation in another clinical trial within three weeks before screening day
Patient will not be allowed to enroll in this trial more than once.
Known microsatellite-instability (MSI-H or dMMR) as evidenced by a standard laboratory practice (e.g. PCR or staining or sequencing etc.)
Prisoners or patients who are involuntarily incarcerated.
Patients who are compulsorily detained for treatment of either a psychiatric or physical(e.g., infectious disease) illness
Facility Information:
Facility Name
University of Heidelberg / NCT
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Ipilimumab, Maraviroc and Nivolumab in Advanced Metastatic Colorectal and Pancreatic Cancer the LUMINESCENCE Trial
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