- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01348412
Hepatic Arterial Chemotherapy With Raltitrexed and Oxaliplatin Versus Standard Chemotherapy in Unresectable Liver Metastases From Colorectal Cancer After Conventional Chemotherapy Failure (HEARTO)
July 12, 2018 updated by: Centre Georges Francois Leclerc
Phase II Randomized Study Comparing the Association of Intraarterial Perfusion of Raltitrexed and Oxaliplatin Versus Standard Chemotherapy Using Intravenous Perfusion for Colorectal Cancer Patient With Metastases Localized to Liver After Failure of Conventional Treatments.
Standard treatment of metastatic colorectal cancers relies on fluoropyrimidines, irinotecan alone or in association with fluoropyrimidines, oxaliplatin in association with fluoropyrimidines, bevacizumab and anti EGFR antibodies.
After failure of classical regimen the national reference frame on the basis of phase II study proposes an association of fluoropyrimidine and mitomycin.
These treatments give response rates of 10-20% with progression free survivals from 2 to 3 months.
Hepatic intra-arterial chemotherapy is logical in the case of isolated hepatic metastases nonaccessible to curative resection: 1) hepatic metastases are vascularized by hepatic arterial system in contrast to nontumoral hepatic parenchyma; 2) arterial perfusion of oxaliplatin leads to a strong extraction by the liver during the first passage, a high intra-tumoral concentration and a low systemic concentration.
So oxaliplatin is a drug of choice for arterial treatment but combination with fluoropyrimidines is impossible because of need for prolonged perfusion.
Floxuridin is not available in France.
Raltitrexed, a definitive inhibitor of the thymidylate synthase, does not require a prolonged perfusion and could be a good substitute.In a previous pilot study we demonstrated the feasibility, safety and efficacy of combination of raltitrexed and oxaliplatin arterial perfusion.
Now we propose a phase II randomized clinical trial to evaluate the efficacy of hepatic arterial infusion of raltitrexed and oxaliplatin association versus standard chemotherapy for patients with metastases of colorectal origin restricted to the liver after failure of conventional chemotherapy.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
31
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Dijon, France, 21000
- Centre Georges Francois Leclerc
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Informed consent signature by the patient-
- Cover by an health insurance
- Age between 18 and 75 years
- Age between 76 et 80 years if patient WHO Status 0
- WHO status of 0 or 1
- Estimated Life expectancy > 3 months
- Hepatic metastases of colorectal cancer confirmed on CT Scan without extra-hepatic metastasis (the presence of asymptomatic primary tumor is tolerated)
- TEP-Scan without fixation outside the liver and the primary tumor
- Histological proven colorectal cancer obtained from primary tumor or the hepatic metastases
- Metastases not accessible to curative hepatectomy (impossible R0 surgery or leaving less than 30 % of residual liver), or requiring a complex, very wide hepatectomy (5 segments or more) and\or risky procedure (RPC Class II)- - Presence of hepatic lesion > 10 mm on CTScan or hepatic MRI
- Failure or arrest of a previous chemotherapy because of intolerance to oxaliplatin, irinotecan, a fluoropyrimidine and/or target therapies (bevacizumab, cetuximab or panitumumab given for tumor expressing wild type Ki-Ras)
- Bilirubinemia< 1,5 times the superior limit of the normal ( N ),
- ASAT and ALAT < 5 N,
- Creatinemia < 1.5 N and creatinine clearance > 65ml/mn,
- Neutrophils > 1,5 x 109/L, platelets 100 x 109/L, hemoglobin > 9 g/dL (patients includables even after red blood cell transfusion)-Reference CTScan +/-MRI performed in 21 days preceding the first cycle of treatment
Exclusion Criteria:
- extra-hepatic metastases (presence of 1 to 3 pulmonary nodules, of a maximal diameter of 5 mm with non specific aspect on CTScan and with no fixation on TEP Scan does not constitute a criterion of exclusion)
- Symptomatic primary colorectal tumor in place
- Contraindication for allergy of rank 3-4 for one of the compounds of chemotherapy- Peripheral neuropathy > 2 (Levy Scale)
- Current participation or in the 30 days preceding the inclusion in the study in another therapeutic trial with an experimental molecule
- Concomitant systemic treatment by immunotherapy, chemotherapy or hormonotherapy- Unbalanced serious illness, unchecked active infection or the other underlying serious disorder susceptible to prevent the patient from receiving the treatment
- Pregnancy (pregnancy test compulsory for the inclusion), breast-feeding
- Intestinal occlusion or sub-occlusion or history of inflammatory intestinal disease
- Other cancer during the 5 years preceding entry in the trial or concomitant (except in situ cancer of the cervix or skin basal cell carcinoma)Patient in custody or under guardianship, Impossibility to adhere to the medical follow-up for geographical, social or psychiatric reason
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: ARM A
Hepatic artery infusion through an implanted arterial catheter of the combination of raltitrexed (3 mg/m ²) and oxaliplatin (100 mg/m ²) every 21 days.
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130 mg/m²Every 21 days
3 mg/m² with a maximum of 6 mg every 21 days
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Active Comparator: ARM B
Intravenous standard chemotherapy.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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progression-free survival
Time Frame: for each patient after the 6 months of treatment
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for each patient after the 6 months of treatment
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Estimate the parameters of tumor perfusion using arterial CT Scan data
Time Frame: for each patient of experimental arm every 9 weeks after the six months of treatment or until progression
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for each patient of experimental arm every 9 weeks after the six months of treatment or until progression
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Estimate the rate of objective response according to the criteria of CHOI and RECIST
Time Frame: for each patient every 9 weeks during the 6 months of treatment or until progression
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for each patient every 9 weeks during the 6 months of treatment or until progression
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Estimate the overall survival which will be compared with the median of overall survival in other studies published in the literature
Time Frame: after all data completion after the end of all patient follow-up (december 2013-anticipated)
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after all data completion after the end of all patient follow-up (december 2013-anticipated)
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Estimate the rate of secondary resectable hepatic metastases
Time Frame: after all data completion after the end of all patient follow-up (december 2013-anticipated)
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after all data completion after the end of all patient follow-up (december 2013-anticipated)
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Estimate the tolerance of the treatment (NCI-CTCAE version 4.0)
Time Frame: For each patient every 21 days during the six months of treatment and for one year of follow up or until progression
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For each patient every 21 days during the six months of treatment and for one year of follow up or until progression
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Estimate the quality of life (QLQ C30) and the fatigue MFI20
Time Frame: after all data completion after the end of all patient follow-up (december 2013-anticipated)
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after all data completion after the end of all patient follow-up (december 2013-anticipated)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 15, 2010
Primary Completion (Actual)
December 15, 2010
Study Completion (Actual)
April 18, 2018
Study Registration Dates
First Submitted
April 27, 2011
First Submitted That Met QC Criteria
May 4, 2011
First Posted (Estimate)
May 5, 2011
Study Record Updates
Last Update Posted (Actual)
July 16, 2018
Last Update Submitted That Met QC Criteria
July 12, 2018
Last Verified
July 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Neoplastic Processes
- Colorectal Neoplasms
- Neoplasm Metastasis
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Folic Acid Antagonists
- Oxaliplatin
- Raltitrexed
Other Study ID Numbers
- 0329-1ghfr09
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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