CCR5-blockade in Metastatic Colorectal Cancer (MARACON)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University Hospital Heidelberg
Information provided by (Responsible Party):
National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier:
NCT01736813
First received: October 24, 2012
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

The surface molecule CCR5 is found on tumor cells within liver metastases of colorectal cancer. Inhibition of this molecule leads to a reduction in growth signals for tumor cells and subsequent slowed or halted tumor growth. The agent for the inhibition of CCR5 has already received FDA approval for treatment of HIV and has shown little side effects and toxicities even on long term treatment. Therefore CCR5-inhibition has the potential of providing non-toxic tumor growth inhibition.


Condition Intervention
Colorectal Cancer
Neoplasm Metastasis
Liver Metastases
Advanced Stage Colorectal Cancer Patients Standard of Care Chemotherapy
Drug: Maraviroc

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Treatment of Advanced Colorectal Cancer Patients With Hepatic Liver Metastases Using the CCR5-Antagonist Maraviroc (Phase I Maracon Trial)

Resource links provided by NLM:


Further study details as provided by National Center for Tumor Diseases, Heidelberg:

Primary Outcome Measures:
  • safety as occurence of adverse events ≥ Grade 3 according to CTCAE, Version 4.0 criteria, that are definitely, probably, or possible related to the administration of the investigational agent [ Time Frame: after eight weeks of treatment ] [ Designated as safety issue: Yes ]
    safety, tolerability and feasibility will be assessed after eight weeks of continuous intake of the CCR5-inhibitor. Safety measures include blood analyses (hematologic, liver function, renal function etc.) and the overall performance status of the patient. Especially infections and infection-related events are investigated.


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: one year after eight weeks of treatment ] [ Designated as safety issue: No ]
    Patients will be evaluated for one year afterwards to assess progression free survival.

  • Tumor response according to the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: after eight weeks of treatment ] [ Designated as safety issue: No ]
    Tumor response will be evaluated after eight weeks of continuous treatment with the CCR5-inhibitor, using the RECIST criteria on MRI images (comparing pre- and post-treatment)

  • Tissue level responses of growth inhibition via the CCR5 axis [ Time Frame: during the first four weeks of treatment ] [ Designated as safety issue: No ]
    The evaluation of tissue alterations within the tumor microenvironment induced by CCR5-inhibition will be performed during the first four weeks of treatment, comparing the pre-treatment tissue situation with the post-treatment situation.

  • Overall survival [ Time Frame: one year after eight weeks of treatment ] [ Designated as safety issue: No ]
    Patients will be evaluated for one year afterwards to assess overall survival.


Biospecimen Retention:   Samples With DNA

Biopsies, Serum and DNA


Estimated Enrollment: 12
Study Start Date: November 2012
Estimated Study Completion Date: November 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
CCR5-inhibitor at 300 mg/bid
colorectal cancer patients with liver metastases (twelve patients treated with 300 mg/bid)
Drug: Maraviroc
Twelve patients with 300 mg/bid
Other Name: Celsentri

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

large university hospital with local private practice referrers

Criteria

Inclusion Criteria:

  • written informed consent (must be available before enrollment in the trial)
  • age ≥ 18 years
  • male or female patient with a history of treated metastatic stage IV colorectal cancer with liver metastases of the primary colorectal cancer
  • histologically confirmed liver metastasis of colorectal cancer with histologically confirmed CCR5 (C-C chemokine receptor type 5) expression in the tumor cells
  • expected survival of at least three months
  • Karnofsky performance status > 70 %
  • patients that have received current standard treatment options (progression or intolerance to oxaliplatin, irinotecan and 5-Fluorouracil with or without treatment combinations of cetuximab and/or bevacizumab or panitumumab)
  • no chemotherapy treatment within the last three weeks
  • within the last 2 weeks prior to study day 1 the following laboratory parameters, which should be within the ranges specified (or as deemed acceptable by trial investigator): absolute neutrophil count (ANC) ≥ 1000/mm3 (≥ 1.0 x 109/L), platelets ≥ 80.000/mm3 (≥ 80 x 109/L), creatinine Clearance limit as assessed by golermular filtration rate > 60 mL/min/1.73m², ALT (alanine transaminase), AST (aspartate transaminase), and total bilirubin all ≤ 5.0 x ULN (upper limit normal)
  • able and willing to give valid written informed consent and to understand character and individual consequences of the clinical trial
  • if the patient is female, she must be of non-childbearing potential, or practice adequate contraception.

Exclusion Criteria:

  • 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 immunosuppressive agents. Topical or inhalational steroids are permitted.
  • Patients taking immunomodulatory medication (Type 1 interferons).
  • Use of any investigational or non-registered product (drug or vaccine) other than the study treatment
  • Patients with single metastatic lesions (intent to resect the metastasis)
  • Patients with metastatic colorectal cancer that have a drastic clinical progression (e.g. from Karnofsky performance 100% to 60%) within the last six weeks before screening cannot participate
  • The patient has 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 psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
  • The patient has concurrent chronic severe medical problems (heart failure, uncontrolled diabetes, bleeding disorder etc.), unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
  • 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.
  • Women of childbearing potential: Refusal or inability to use effective means of contraception
  • 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
  • Participation in other clinical trials or observation period of competing trials, respectively
  • No subject will be allowed to enroll in this trial more than once.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01736813

Locations
Germany
National Center for Tumor Diseases, Department of Medical Oncology
Heidelberg, Baden-Württemberg, Germany, 69120
Sponsors and Collaborators
National Center for Tumor Diseases, Heidelberg
University Hospital Heidelberg
Investigators
Principal Investigator: Niels Halama, MD National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany
Study Director: Dirk Jaeger, MD National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Germany
  More Information

No publications provided

Responsible Party: National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier: NCT01736813     History of Changes
Other Study ID Numbers: MARACON-001, 2012-000861-18
Study First Received: October 24, 2012
Last Updated: July 1, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by National Center for Tumor Diseases, Heidelberg:
colorectal cancer
liver metastases
chemotherapy
chemokine
CCR5 inhibition

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases

ClinicalTrials.gov processed this record on July 10, 2014