Phase III clinical trial of FOLF(HA)iri vs FOLFIRI forsecond or third line therapy in irinotecan-naïve patients with metastaticcolorectal cancer
- Conditions
- Metastatic colorectal cancer (mCRC)MedDRA version: 17.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2010-020348-36-BG
- Lead Sponsor
- Alchemia Oncology Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 390
1) Metastatic colorectal cancer with disease progression after first or second line chemotherapy (adjuvant chemotherapy is considered first line chemotherapy if progression occurs within 6 months of the end of the adjuvant chemotherapy). See Section 4.2 of the study protocol for prior chemotherapy requirements and for required documentation of disease progression.
2) Irinotecan naïve, i.e. no prior irinotecan.
3) ECOG performance status of 0 or 1.
4) Measurable disease, i.e. at least one measurable metastatic lesion (=1cm on spiral CT or MRI).
5) Histological proof of colorectal cancer (from either primary or metastatic lesion).
6) 18 years of age and older.
7) Adequately recovered from and at least 4 weeks after recent surgery or chemotherapy to randomization (the start of screening defined as the date of the first screening procedure; screening includes CT or MRI scans as defined below).
8) At least 4 weeks after treatment with a biologic monotherapy from last dose to randomization.
9) Women of child-bearing potential (WOCBP) and male partners of WOCBP must agree to use adequate contraception. WOCBP and male partners of WOCBP must agree to use adequate contraception prior to study entry, throughout the study and for 3 months after cessation of protocol therapy. WOCBP include women who have experienced menarche and who have not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or are not postmenopausal (defined as amenorrhoea > 12 consecutive months). Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or who are practicing abstinence or whose partner is sterile (eg., vasectomized) should be considered to be of child-bearing potential.
10) Patient consent obtained and signed according to local Institutional and/or University Human Experimentation Committee requirements and/or a central Institutional Review Board (IRB) or other as appropriate.
11) CT or MRI scan of chest/abdomen/pelvis with other scans as necessary to document all sites of disease, done within 21 days prior to randomization. Contrast enhancement should be used if no contraindication. The same imaging method should be used for the patient throughout the entire study (e.g. if a patient starts with CT scans all subsequent imaging should be with CT scans).
12) Hematology done within 14 days prior to randomization:
a. Absolute Neutrophil Count (ANC) >1.5 x 10(9)/L
b. Platelets > 100 x 10(9)/L
c. Hemoglobin > 100g/L (transfusions may be used to raise hemoglobin to >100g/L, but there must be no evidence of active bleeding)
13) Chemistry done within 14 days prior to randomization:
a. AST = 2.5 X ULN (= 5 X ULN if elevation thought to be related to hepatic metastatic disease)
b. Alkaline phosphatase < 5 x ULN
c. Serum creatinine < 1.5 x ULN
d. Total bilirubin = 2.0 mg/dl. (= 34.2 µmol/L)
e. Negative serum or urine pregnancy test if a WOCBP.
14) Patients must be accessible for treatment and follow-up, including complete documentation of the treatment, toxicity, and follow-up.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 290
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
1) History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for > 5 years.
2) Locally advanced or recurrent disease only, i.e. patients may have locally advanced or recurrent disease, but must also have measurable, metastatic disease.
3) Unsuitability for irinotecan including known Gilbert’s syndrome, active inflammatory bowel disease or chronic diarrhea = grade 2.
4) Abdominal or pelvic radiation therapy (including treatment with SIR-Spheres/Sirtex) within the last 12 months (i.e. the last day of prior radiation therapy must be 12 months prior to the start of screening; defined as the date of the first screening procedure).
5) Women who are pregnant or breastfeeding.
6) Any condition (e.g., psychological, geographical) that would render the protocol treatment dangerous, impair the ability of the patient to receive protocol therapy or that would impair compliance with the protocol.
6) Significant cardiac disease, defined as myocardial infarction within 3 months prior to randomization, congestive heart failure classified by the New York Heart Association as Class III or IV (Appendix A.9), uncontrolled cardiac arrhythmias, poorly controlled or unstable angina, or electrocardiographic evidence of acute ischemia.
7) Untreated or symptomatic brain or central nervous system (CNS) metastases (head CT or MRI is required only in the presence of neurological symptoms or signs consistent with cerebral metastases).
8) Presence of pleural effusion or ascites requiring therapeutic thoracocentesis or paracentesis and pleural effusion or ascites described in the radiological summaries as signoficant.
9) Current partial or complete bowel obstruction.
10) Concomitant active infection.
11) Enrolled in any other investigational trial, unless treatment in that trial has been discontinued at least 30 days prior to start of screening, defined as the date of the first screening procedure, and that treatment was fully compliant with the ACO-002 entry criteria. Patients who progressed in a previous trial and are still in follow up - will require case by case discussion with the Medical Monitor and Alchemia.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate that FOLF(HA)iri is superior to FOLFIRI in prolonging progression free survival (PFS) of irinotecan-naïve patients with metastatic colorectal cancer in the second or third line treatment setting.;Secondary Objective: To compare FOLF(HA)iri and FOLFIRI with respect to:<br>• Patient safety, including incidence of severe (Grade 3/4) toxicity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.02).<br><br>To compare FOLF(HA)iri and FOLFIRI with respect to:<br>• Overall survival (OS)<br>• Overall response rate (RR=CR+PR);Primary end point(s): The primary efficacy outcome is PFS based on tumor response assessments established by the independent radiology reviewers;Timepoint(s) of evaluation of this end point: The primary analysis of PFS will be completed after 350 progressions or deaths have been confirmed
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Overall Survival(OS)<br>Response Rate (RR);Timepoint(s) of evaluation of this end point: Secondary endpoints are to be evaluated at the time of the final OS analysis