Clincosm LogoSign in Get a demo

NEXIRI2: Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors

Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle (Other)
Overall Status
Completed
CT.gov ID
NCT01715441
Collaborator
(none)
173
Enrollment
9
Locations
3
Arms
36
Actual Duration (Months)
19.2
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this multicenter randomized phase II trial is to determine the efficacy of sorafenib and irinotecan combination versus irinotecan monotherapy or versus sorafenib monotherapy in metastatic colorectal cancer patients with KRAS mutated tumors after failure of all active drugs known to be effective.

Condition or Disease Intervention/Treatment Phase
  • Drug: Sorafenib and irinotecan combination
  • Drug: Sorafenib monotherapy
  • Drug: Irinotecan monotherapy
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
173 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II Trial Assessing Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors After Failure of All Drugs Known to be Effective
Actual Study Start Date :
Sep 1, 2012
Actual Primary Completion Date :
Mar 1, 2015
Actual Study Completion Date :
Sep 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Irinotecan monotherapy

Intravenous infusion irinotecan 180 mg/m2 over 90 minutes (D1=D15) with cross over to irinotecan and sorafenib combination at progression.

Drug: Irinotecan monotherapy
Active Comparator: Sorafenib monotherapy

Oral sorafenib 400 mg twice daily (total dose 800 mg/day) with cross over to irinotecan and sorafenib combination at progression

Drug: Sorafenib monotherapy
Experimental: Sorafenib and irinotecan combination

Intravenous infusion irinotecan 120 mg/m2 over 90 minutes (D1=D15) at Cycle 1, 150 mg/m² at C2 if no diarrhea > grade 1 and no other toxicity > grade 2, and 180 mg/m² at C3 in the same conditions Oral sorafenib 400 mg twice daily (total dose 800 mg/day) from C1. 1 cycle = 15 days and 1 course = 4 weeks.

Drug: Sorafenib and irinotecan combination

Outcome Measures

Primary Outcome Measures

  1. Non-progression rate [At 2 months]

    To evaluate the non-progression rate at 2 months according to RECIST criteria (Version 1.1)

Secondary Outcome Measures

  1. Disease control rate [At 2 months]

    According to RECIST criteria (Version 1.1)

  2. Treatment-related toxicity [At 6 months]

    According to NCI CTC V4.0

  3. Overall survival [At 6 months]

    Overall survival is defined as the time from the date of inclusion to the date of death from any cause.

  4. Quality of life questionnaire [6 months]

    Using the EORTC QLQ-C30 questionnaire

  5. Progression Free Survival [At 6 months]

    Progression Free Survival is defined as the time from the date of inclusion to first documentation of objective tumor progression or to death due to progression.

  6. Response rate [At 2 months]

    According to RECIST criteria (Version 1.1)

Other Outcome Measures

  1. Cmax and Tmax of sorafenib and irinotecan [Up to 3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Male or female ≥ 18 years old

  • Histologically confirmed diagnosis of colorectal cancer

  • Asymptomatic or resected primary tumor

  • Metastatic colorectal cancer patient not eligible for curative surgery

  • At least one target lesion:

  • Unidimensionally measurable on cross-sectional imaging

  • In an area not previously irradiated

  • Disease progression after failure of active drugs (5-Fu or 5-Fu prodrugs, irinotecan, oxaliplatin, bevacizumab)

  • Patients with bone metastases are eligible if they have other measurable lesions

  • WHO performance status ≤ 2

  • Confirmation of KRAS mutation in codons 12 or 13 in the primary tumor or metastases

  • Total bilirubin ≤ 1.5 ULN, ALT or AST ≤ 2.5 ULN (or < 5 in case of liver impairment)

  • Haemoglobin ≥ 10 g/dL, neutrophils ≥ 1,500/mm3, platelets ≥ 100,000/mm3

  • Serum creatinine ≤ 1.5 ULN

  • Negative pregnancy test in women of childbearing potential

  • Use of an effective contraceptive method during the whole treatment and up to 3 months after the completion of treatment in males and females

  • Life expectancy of at least 3 months

  • Informed consent signed prior any study specific procedures

  • Tumor evaluation should be performed within 3 weeks prior to starting treatment

Exclusion Criteria:

  • History of Gilbert's syndrome

  • Symptomatic brain metastases or carcinomatous meningitis

  • Bone-only metastases

  • History or presence of other cancers within the past 5 years (except curatively treated non-melanoma skin cancer and in situ cervical cancer)

  • Prior surgery or radiotherapy within 4 weeks before entering the study

  • Cardiac arrhythmia requiring treatment (except for beta-blockers and digoxin), unstable cardiac disease, myocardial infarction within the previous 6 months, > grade II NYHA heart failure, uncontrolled hypertension

  • Kalemia lower than normal serum potassium value

  • From ECG, QTc interval > 470 ms

  • History of acute or chronic pancreatitis

  • History of epileptic seizures requiring long-term anticonvulsant therapy

  • History of organ transplantation with use of immunosuppression therapy

  • Severe bacterial or fungal infection (Grade > 2 NCI-CTCAE v.4.0)

  • Known HIV infection

  • Long-term use of CYP 3A4 enzyme-inducing agents such as rifampicin, St. John's Wort (hypericum perforatum), phenytoin, carbamazepine, phenobarbital, dexamethasone, and ketoconazole

  • Pregnant or breastfeeding women

  • Bowel malabsorption or extended bowel resection that could affect the absorption of sorafenib, occlusive syndrome, inability to take oral medications

  • Inflammatory bowel disease with chronic diarrhea (NCI-CTCAE v.4.0)

  • Participation in another clinical trial 30 days prior to study entry

  • Concurrent treatment with any other investigational product or anticancer therapy (except for irinotecan or sorafenib)

  • Psychological, social, geographical disorders or any other condition that would preclude study compliance (treatment administration and study follow-up).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hôpital AVICENNE Bobigny France 93009
2 Centre François Baclesse Caen France 14076
3 Centre Oscar Lambret Lille France 59020
4 Centre Léon Bérard Lyon France 69373
5 Hôpital LA TIMONE Marseille France 13365
6 CRLC Val d'Aurelle-Paul Lamarque Montpellier France 34298
7 C.H.U. de REIMS Reims France 51092
8 CHU Charles Nicolle Rouen France 76038
9 Institut de Cancérologie de l'Ouest - René Gauducheau St. Herblain France 44805

Sponsors and Collaborators

  • Institut du Cancer de Montpellier - Val d'Aurelle

Investigators

  • Principal Investigator: Emmanuelle SAMALIN, MD, CRLC Val d'Aurelle-Paul Lamarque
  • Study Chair: Marc YCHOU, MD,, CRLC Val d'Aurelle

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Institut du Cancer de Montpellier - Val d'Aurelle
ClinicalTrials.gov Identifier:
NCT01715441
Other Study ID Numbers:
  • NEXIRI2
  • 2012-000644-94
First Posted:
Oct 29, 2012
Last Update Posted:
Aug 22, 2019
Last Verified:
Mar 1, 2015
Keywords provided by Institut du Cancer de Montpellier - Val d'Aurelle
Metastatic colorectal cancer patients
KRAS mutation
Sorafenib
Additional relevant MeSH terms:
Colorectal Neoplasms
Irinotecan
Sorafenib

Study Results

No Results Posted as of Aug 22, 2019