Colorectal CancerPhase 2HEARTONCT01348412
Hepatic Arterial Chemotherapy With Raltitrexed and Oxaliplatin Versus Standard Chemotherapy in Unresectable Liver Metastases From Colorectal Cancer After Conventional Chemotherapy Failure
A Phase 2 study testing oxaliplatin, raltitrexed and other intravenous chemotherapy drugs in people with Colorectal Cancer and Liver Metastases, run by Centre Georges Francois Leclerc at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer, Liver Metastases
- What is being tested?
- oxaliplatin, raltitrexed and other intravenous chemotherapy drugs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteFrance
- Study dates
- 15 Dec 2010to 18 Apr 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 15Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Colorectal Cancer, Liver Metastases
- Being tested
- oxaliplatin, raltitrexed, other intravenous chemotherapy drugs
- Keywords
- non resectable metastases, liver of colic or rectal origin, after failure of the conventional treatments
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oxaliplatinDrug
130 mg/m²Every 21 days
raltitrexedDrug
3 mg/m² with a maximum of 6 mg every 21 days
other intravenous chemotherapy drugsDrug
| Study group | Role | What they receive |
|---|---|---|
| ARM A | Experimental | 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. Receives: Drug: oxaliplatin; Drug: raltitrexed |
| ARM B | Active comparator | Intravenous standard chemotherapy. Receives: Drug: other intravenous chemotherapy drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival
Measured: for each patient after the 6 months of treatment
Secondary outcomes (6)
Estimate the parameters of tumor perfusion using arterial CT Scan data
Measured: for each patient of experimental arm every 9 weeks after the six months of treatment or until progression
Estimate the rate of objective response according to the criteria of CHOI and RECIST
Measured: for each patient every 9 weeks during the 6 months of treatment or until progression
Estimate the overall survival which will be compared with the median of overall survival in other studies published in the literature
Measured: after all data completion after the end of all patient follow-up (december 2013-anticipated)
Estimate the rate of secondary resectable hepatic metastases
Measured: after all data completion after the end of all patient follow-up (december 2013-anticipated)
Estimate the tolerance of the treatment (NCI-CTCAE version 4.0)
Measured: For each patient every 21 days during the six months of treatment and for one year of follow up or until progression
Estimate the quality of life (QLQ C30) and the fatigue MFI20
Measured: after all data completion after the end of all patient follow-up (december 2013-anticipated)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2011 (estimated)
- Study start15 Dec 2010
- Primary completion15 Dec 2010
- Study completion18 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Georges Francois Leclerc
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute, France, Hospira, now a wholly owned subsidiary of Pfizer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01348412
- Sponsor's protocol ID
- 0329-1ghfr09
- Acronym
- HEARTO
- Status last verified
- Jul 2018
- First submitted
- 27 Apr 2011
- Last updated
- 16 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT01348412
- Acronym / sponsor ID
- HEARTO / 0329-1ghfr09
- Conditions
- Colorectal Cancer, Liver Metastases
- Keywords
- non resectable metastases, liver of colic or rectal origin, after failure of the conventional treatments
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Centre Georges Francois LeclercUniversity, hospital or other
- Collaborators
- National Cancer Institute, France, Hospira, now a wholly owned subsidiary of Pfizer
- Study start
- 15 Dec 2010 (actual)
- Primary completion
- 15 Dec 2010 (actual)
- Study completion
- 18 Apr 2018 (actual)
- First posted
- 5 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM A | Experimental | Drug: oxaliplatin, Drug: raltitrexedHepatic 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. |
| ARM B | Active comparator | Drug: other intravenous chemotherapy drugsIntravenous standard chemotherapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oxaliplatin130 mg/m²Every 21 days | Drug | ARM A |
| raltitrexed3 mg/m² with a maximum of 6 mg every 21 days | Drug | ARM A |
| other intravenous chemotherapy drugs | Drug | ARM B |
Primary outcome
progression-free survival
Time frame: for each patient after the 6 months of treatment
6 secondary outcomes
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
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
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)
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)
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
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing oxaliplatin, raltitrexed and other intravenous chemotherapy drugs in people with Colorectal Cancer and Liver Metastases, run by Centre Georges Francois Leclerc at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression-free survival (time frame: for each patient after the 6 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2018.