Hepatic Arterial Chemotherapy With Raltitrexed and Oxaliplatin Versus Capecitabine Plus Mitomycin (HEARTO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Centre Georges Francois Leclerc
Sponsor:
Collaborators:
National Cancer Institute, France
Hospira, Inc.
Information provided by (Responsible Party):
Centre Georges Francois Leclerc
ClinicalTrials.gov Identifier:
NCT01348412
First received: April 27, 2011
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

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 oral capecitabine and intravenous mitomycin for patients with metastases of colorectal origin restricted to the liver after failure of conventional chemotherapy.


Condition Intervention Phase
Colorectal Cancer
Liver Metastases
Drug: oxaliplatin
Drug: raltitrexed
Drug: mitomycin C
Drug: capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Randomized Study Comparing the Association of Intraarterial Perfusion of Raltitrexed and Oxaliplatin Versus Oral Capecitabine and Mitomycin Using Intravenous Perfusion for Colorectal Cancer Patient With Metastases Localized to Liver After Failure of Conventional Treatments.

Resource links provided by NLM:


Further study details as provided by Centre Georges Francois Leclerc:

Primary Outcome Measures:
  • progression-free survival [ Time Frame: for each patient after the 6 months of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: December 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: oxaliplatin
130 mg/m²Every 21 days
Drug: raltitrexed
3 mg/m² with a maximum of 6 mg every 21 days
Active Comparator: ARM B
Combination of intravenous mitomycin-C (7 mg/m ²) every 42 days and oral capecitabine (2000 mg/m ²) 2 weeks over 3 every 42 days.
Drug: mitomycin C
7 mg/m² administered every 42 days
Drug: capecitabine
every day from day 2 to 15 then from day 23 to 36

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01348412

Contacts
Contact: Jérémy SKRZYPSKI, PHD 3 80 73 75 00 (3461) ext +33 jskrzypski@cgfl.fr
Contact: Sandrine Tiago, MD 3 45 34 80 51 ext +33 stiago@cgfl.fr

Locations
France
Centre Georges François Leclerc Recruiting
Dijon, France, 21000
Sponsors and Collaborators
Centre Georges Francois Leclerc
National Cancer Institute, France
Hospira, Inc.
  More Information

No publications provided

Responsible Party: Centre Georges Francois Leclerc
ClinicalTrials.gov Identifier: NCT01348412     History of Changes
Other Study ID Numbers: 0329-1ghfr09
Study First Received: April 27, 2011
Last Updated: September 25, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Georges Francois Leclerc:
non resectable metastases
liver of colic or rectal origin
after failure of the conventional treatments

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases
Mitomycins
Mitomycin
Oxaliplatin
Raltitrexed
Capecitabine
Fluorouracil
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014