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Trial record 87 of 297 for:    colon cancer AND Capecitabine AND chemotherapy

De-escalation Chemotherapies Versus Escalation in Non Pre-treated Unresectable Patients With Metastatic Colorectal Cancer (HIGH-LIGHT)

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ClinicalTrials.gov Identifier: NCT02842580
Recruitment Status : Terminated (Inclusion rythm too slow.)
First Posted : July 25, 2016
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive

Brief Summary:

The intensity of tumour response appears to be correlated with the feasibility and the duration of a therapeutic pause or of a reduced maintenance therapy maintained until progression in patients initially controlled by so-called "induction" chemotherapy. Bevacizumab combined with cytotoxic chemotherapy (5-FU, irinotecan and/or oxaliplatin) has shown that it is possible to improve the tumour response rate and patient prognosis in 1st and 2nd lines. With a very favourable safety profile , it is an excellent candidate as induction treatment and also as maintenance treatment. Prospective data from recent trials have actually demonstrated improvement in PFS and/or overall survival with bevacizumab maintenance alone or in combination with 5FU (or capecitabine) after induction chemotherapy (FOLFIRI or FOLFOX + bevacizumab).

At the same time, the maintenance of anti-angiogenic pressure after progression in 1st line metastatic has demonstrated its benefit in terms of PFS and overall survival. Bevacizumab maintenance in 2nd line metastatic, despite progression, thus appears to be a valid strategy.


Condition or disease Intervention/treatment Phase
Colorectal Neoplasms Drug: 5 FLUOROURACYL Drug: acide folinique Drug: irinotecan Drug: Oxaliplatin Drug: capécitabine Drug: bevacizumab Phase 2

Detailed Description:
Thus, the objective of this work is to combine continuous blocking of angiogenesis by bevacizumab given on the first 3 metastatic lines in a randomised phase II trial evaluating a "descending" strategy of immediate optimisation by 4 cycles of FOLFOXIRI-bevacizumab and 4 cycles of FOLFIRI-bevacizumab, followed by maintenance treatment with 5FU-bevacizumab until progression (re-introduction of induction in case of progression) and evaluate an "ascending" strategy with 5FU-bevacizumab immediately followed, at progression, by the introduction of irinotecan, then oxaliplatin, with maintenance of blocking of angiogenesis by bevacizumab.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Study Assessing the Efficacy and Safety of 2 Therapeutic Strategies Combining Bevacizumab With Chemotherapy: De-escalation Versus Escalation in Patients With Non-pretreated Unresectable Metastatic Colorectal Cancer
Actual Study Start Date : September 2016
Actual Primary Completion Date : March 2018
Actual Study Completion Date : March 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Standard arm (escalation strategy - arm A)
LV5FU2 (5 FLUOROURACYL)+avastin. After progression: FOLFIRI + avastin. after the 2nd progression:FOLFOX4 (eloxatine)+ avastin.
Drug: 5 FLUOROURACYL

Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as a 2 hr infusion.

The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).

The cycles will last 14 days. For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.

Other Name: FLUOROURACILE EBEWE

Drug: acide folinique
200 mg/m² if Elvorine
Other Name: ELVORINE

Drug: irinotecan

Irinotecan is administered IV at a dose of 180 mg/m² over 90 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with irinotecan.

The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).

The cycles will last 14 days.

Other Name: CAMPTO

Drug: Oxaliplatin

Oxaliplatin is administered IV at a dose of 85 mg/m² over 120 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with oxaliplatin.

The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).

The cycles will last 14 days.

Other Name: ELOXATINE 5 mg/ml

Drug: capécitabine
For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.
Other Name: XELODA

Drug: bevacizumab
Bevacizumab is administered IV at a dose of 5 mg/kg over 90 min at cycle 1, then 60 min at cycle 2 and 30 min in subsequent cycles. Bevacizumab is administered every 2 weeks before the start of chemotherapy
Other Name: AVASTIN

Experimental: Experimental arm (de-escalation strategy -arm B)
(4 cycles of FOLFOXIRI (campto) + avastin and 4 cycles of FOLFIRI + avastin) is followed by maintenance with capecitabine
Drug: 5 FLUOROURACYL

Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as a 2 hr infusion.

The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).

The cycles will last 14 days. For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.

Other Name: FLUOROURACILE EBEWE

Drug: acide folinique
200 mg/m² if Elvorine
Other Name: ELVORINE

Drug: irinotecan

Irinotecan is administered IV at a dose of 180 mg/m² over 90 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with irinotecan.

The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).

The cycles will last 14 days.

Other Name: CAMPTO

Drug: Oxaliplatin

Oxaliplatin is administered IV at a dose of 85 mg/m² over 120 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with oxaliplatin.

The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).

The cycles will last 14 days.

Other Name: ELOXATINE 5 mg/ml

Drug: capécitabine
For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.
Other Name: XELODA

Drug: bevacizumab
Bevacizumab is administered IV at a dose of 5 mg/kg over 90 min at cycle 1, then 60 min at cycle 2 and 30 min in subsequent cycles. Bevacizumab is administered every 2 weeks before the start of chemotherapy
Other Name: AVASTIN




Primary Outcome Measures :
  1. The primary objective is the percentage of patients without failure of the strategy 16 months after the randomization. [ Time Frame: 16 months after randomization ]

    The failure of the strategy is defined by:

    • Progression (under certain condition) using RECIST version 1.1
    • Death (all causes)
    • Toxicity leading to definitive stop of chemotherapy (oxaliplatine and/or irinotecan).


Secondary Outcome Measures :
  1. Best response rate (using RECIST version 1.1) at 16 months [ Time Frame: 16 months after randomization ]
    Assessed on the CT scans performed during treatment

  2. Overall survival (OS) at 2 years and at 3 years [ Time Frame: 2 years and 3 years ]
  3. Progression free survival (PFS) at 2 years and at 3 years [ Time Frame: 2 years and 3 years ]
    Time between the date of randomization and the date of the first radiologic progression or death (all causes)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Metastatic colorectal cancer, histologically proven (on primary tumour and/or metastases)
  • Unresectable and non-pretreated metastases
  • BRAF wild-type
  • Patient considered able to receive 3 lines of chemotherapy
  • At least one measurable target lesion > 1 cm according to RECIST 1.1 (Appendix 4)
  • Tumour assessment according to RECIST, performed 4 weeks or less prior to randomization
  • Age ≥ 18 years
  • WHO performance status ≤ 2 (Appendix 5)
  • No major surgery within 4 weeks prior to randomisation. Wound healing must be complete
  • Life expectancy greater than 3 months
  • Laboratory tests: Neutrophils ≥ 1500/mm3, platelets ≥ 100,000/mm3, haemoglobin > 9 g/dL
  • Creatinine clearance > 30 mL /min (capecitabine dose modification if the creatinine clearance < 30-50 mL/min), serum creatinine < 1.25 x ULN
  • Liver function tests: bilirubin < 1.25 x ULN, AST/ALT < 5 x ULN
  • Women of childbearing age and men (who have sexual relations with women of childbearing age) must agree to use effective contraception without interruption throughout the duration of treatment and for 6 months after the last administration
  • Signed informed consent

Exclusion Criteria:

  • Patient with a potentially resectable colorectal cancer; i.e. for whom the goal of chemotherapy would be to make all metastases resectable
  • Patients with symptomatic metastases
  • Patient with aggressive disease and a large tumour volume
  • Active gastroduodenal ulcer, wound or bone fracture
  • At least one of the following laboratory values: Neutrophils <1500/mm3, platelets < 100,000/mm3, haemoglobin < 9 g/dL, total bilirubin > 1.5 N, alkaline phosphatase > 2.5 N (or > 5 N in case of hepatic involvement), serum creatinine > 1.5 N, 24 hr proteinuria > 1 g
  • Chronic inflammatory bowel disease, extensive resection of the small bowel
  • Clinically significant coronary artery disease or a history of myocardial infraction within the last 6 months. Uncontrolled hypertension while receiving chronic medication
  • Abdominal or major extra-abdominal surgical procedure (except diagnostic biopsy) or radiation within 4 weeks before starting treatment
  • Previous treatment with an anti-angiogenic or irinotecan
  • Known or suspected central nervous system metastasis CNS metastases, or suspected CNS metastases
  • Other previous malignancies within 5 years, except for basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix - Peritoneal macro-nodular carcinomatosis
  • History of haemoptysis ≥ grade 2 (defined as ≥ 2.5 mL of bright red blood per episode) in the month prior to inclusion
  • Known hypersensitivity to any component of bevacizumab or to one of the study treatments
  • Active infection requiring intravenous antibiotics at start of treatment
  • History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to treatment start
  • Pregnant or breastfeeding women
  • Concomitant participation in another clinical study involving a drug during the treatment phase and 30 days before starting the study treatment
  • Patient unable to undergo medical treatment for geographical, social, psychological or legal reasons.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02842580


Locations
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France
Hopital Pierre Oudot - Service de Gastroenterologie
Bourgoin-Jallieu, France, 38300
Ch de Cholet - Service Maladies de L4Appareil Digestif Du Dr Kaasis
Cholet, France, 49325
Chd Vendee - Service D'Hge
La Roche-sur-Yon, France, 85925
Ch Annecy Genevois - Service Hge
Pringy, France, 74374
CH - Annecy Genevois
Pringy, France
Chu Robert Debre - Medecine Ambulatoire-Cancerologie
Reims CEDEX, France, 51092
CHU Robert DEBRE
Reims, France
Chu Charles Nicolle - Service D'Hge
Rouen CEDEX 01, France, 76031
Hopital Prive Saint Gregoire - Service de Radiotherapie
Saint-Grégoire, France, 35768
Centre Hospitalier de St Malo - Service Hepato-Gastro-Enterologie
Saint-Malo, France, 35403
Chu de Saint Etienne-Hopital Nord - Service Hge
Saint-Priest-en-Jarez, France, 42270
Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Investigators
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Principal Investigator: Jean Marc PHELIP, MD-PhD CHU St Etienne

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Responsible Party: Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier: NCT02842580     History of Changes
Other Study ID Numbers: PRODIGE 45
First Posted: July 25, 2016    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Federation Francophone de Cancerologie Digestive:
colorectal
cancer
metastasis
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Colonic Diseases
Capecitabine
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Oxaliplatin
Irinotecan
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors