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Colorectal NeoplasmsPhase 2HIGH-LIGHTNCT02842580

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

A Phase 2 study testing 5 FLUOROURACYL, acide folinique and irinotecan in people with Colorectal Neoplasms, run by Federation Francophone de Cancerologie Digestive at 11 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Neoplasms
What is being tested?
5 FLUOROURACYL, acide folinique and irinotecan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
11 sitesFrance
Study dates
Sep 2016to Oct 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

France11 sites
  • Hopital Pierre Oudot - Service de Gastroenterologie

    Bourgoin, 38300

  • Ch de Cholet - Service Maladies de L4Appareil Digestif Du Dr Kaasis

    Cholet, 49325

  • Chd Vendee - Service D'Hge

    La Roche-sur-Yon, 85925

  • Ch Annecy Genevois - Service Hge

    Pringy, 74374

  • CH - Annecy Genevois

    Pringy

  • Chu Robert Debre - Medecine Ambulatoire-Cancerologie

    Reims, 51092

  • CHU Robert DEBRE

    Reims

  • Chu Charles Nicolle - Service D'Hge

    Rouen, 76031

  • Hopital Prive Saint Gregoire - Service de Radiotherapie

    Saint-Grégoire, 35768

  • Chu de Saint Etienne-Hopital Nord - Service Hge

    Saint-Priest-en-Jarez, 42270

  • Centre Hospitalier de St Malo - Service Hepato-Gastro-Enterologie

    St-Malo, 35403

Other trials in France

About this study

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

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.

Read the 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.

Being tested
5 FLUOROURACYL, acide folinique, irinotecan, Oxaliplatin, capécitabine
Keywords
colorectal, cancer, metastasis
Medical subject headings
Colorectal Neoplasms, Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 5 FLUOROURACYLDrug

    Also called FLUOROURACILE EBEWE

    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.

  • acide foliniqueDrug

    Also called ELVORINE

    200 mg/m² if Elvorine

  • irinotecanDrug

    Also called CAMPTO

    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.

  • OxaliplatinDrug

    Also called ELOXATINE 5 mg/ml

    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.

  • capécitabineDrug

    Also called XELODA

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

  • bevacizumabDrug

    Also called AVASTIN

    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

Study groups in NCT02842580
Study groupRoleWhat they receive
Standard arm (escalation strategy - arm A)Active comparatorLV5FU2 (5 FLUOROURACYL)+avastin. After progression: FOLFIRI + avastin. after the 2nd progression:FOLFOX4 (eloxatine)+ avastin.
Receives: Drug: 5 FLUOROURACYL; Drug: acide folinique; Drug: irinotecan; Drug: Oxaliplatin; Drug: capécitabine; Drug: bevacizumab
Experimental arm (de-escalation strategy -arm B)Experimental(4 cycles of FOLFOXIRI (campto) + avastin and 4 cycles of FOLFIRI + avastin) is followed by maintenance with capecitabine
Receives: Drug: 5 FLUOROURACYL; Drug: acide folinique; Drug: irinotecan; Drug: Oxaliplatin; Drug: capécitabine; Drug: bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Primary Objective Was the Percentage of Patients Without Failure of the Strategy 16 Months After the Randomization.

    The failure of the strategy is defined by the following events:

    • Progression (under certain condition) using RECIST version 1.1 and defined as a 20% increase in the sum of the longest diameter of target lesions compared the little sum of diameters observed durin the study (NADIR), or a measurable increase in a nontarget lesion, or the appearance of new lesions
    • Death (all causes)
    • Toxicity leading to definitive stop of chemotherapy (oxaliplatine and/or irinotecan).

    Measured: 16 months after randomization

Secondary outcomes (3)
  1. Best Response Rate (Using RECIST Version 1.1)

    Best response derived from all the CT scans performed during treatment and based on RECIST 1.1 definition of response.

    Measured: At 16 months

  2. Overall Survival (OS)

    Overall survival was defined as the time from the date of the patient's inclusion to the patient's death (all causes). For alive patients the date of the latest news was taken into account

    Measured: Up to 3 years after the treatment start

  3. Progression Free Survival (PFS)

    The progression-free survival is the time from inclusion to the first radiological progression or death (all causes). For patients alive without progression date of last news will be considered.

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions compared the little sum of diameters observed durin the study (NADIR), or a measurable increase in a nontarget lesion, or the appearance of new lesions

    Measured: up to 24 months after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jul 2016 (estimated)
  2. Study startSep 2016
  3. Primary completionOct 2020
  4. Study completionOct 2020

Why it stopped: Inclusion rythm too slow.

Resources

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
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02842580
Sponsor's protocol ID
PRODIGE 45
Acronym
HIGH-LIGHT
Status last verified
Jul 2024
First submitted
13 Jul 2016
Last updated
10 Jul 2024
Data monitoring committee
Yes
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 5 FLUOROURACYL, acide folinique and irinotecan in people with Colorectal Neoplasms, run by Federation Francophone de Cancerologie Digestive at 11 sites 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 18 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: stopped early, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites 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?

Yes. Results are posted in the registry (first posted 10 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

The Primary Objective Was the Percentage of Patients Without Failure of the Strategy 16 Months After the Randomization. (time frame: 16 months after randomization). 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 10 Jul 2024.

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