E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with metastatic colorectal cancer, who have not previously received systemic treatment for metastatic disease. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055114 |
E.1.2 | Term | Colon cancer metastatic |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
First step: To determine the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT) and the recommended dose of erlotinib in combination with fixed doses of bevacizumab, capecitabine, and oxaliplatin. Second step: To assess the preliminary antitumor activity in terms of overall response rate (complete and partial responses) of erlotinib in combination with bevacizumab, capecitabine, and oxaliplatin |
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E.2.2 | Secondary objectives of the trial |
To evaluate toxicity and the safety profile of the combination. To evaluate duration of response (DR), time to progression (TTP), time to treatment failure (TTF), and overall survival (OS). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically proven diagnosis of colorectal cancer 2. Metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease 3. Age >= 18 4. ECOG Performance Status 0-1 (Appendix III) 5. Life expectancy of at least 12 weeks 6. Measurable and/or evaluable lesions according to RECIST criteria 7. Laboratory requirements: &#61485;Neutrophils >=1.5 x 10(9)/L and Platelets >=100 x 10(9)/L &#61485;Total bilirubin <=1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) <=2.5 x UNL, or <=5 x UNL in case of liver metastases, alkaline phosphatase <=2.5 x UNL, <=5 x UNL in case of liver metastases, <=10 x UNL in case of bone metastases. &#61485; Creatinine clearance >50 mL/min or serum creatinine <=1.5 x UNL) &#61485; Urine dipstick of proteinuria <2+. Patients discovered to have >=2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate <=1 g of protein/24 hr. 8. Written informed consent. 9. Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating center |
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E.4 | Principal exclusion criteria |
1. Radiotherapy to any site within 4 weeks before the study. 2. Prior adjuvant chemotherapy with an oxaliplatin-containing regimen. 3. Symptomatic and/or unstable pre-existing brain metastases. 4. History of inflammatory bowel disease and/or acute/subacute bowel occlusion. 5. Serious non-healing wound or ulcer. 6. Evidence of bleeding diathesis or coagulopathy. 7. Uncontrolled hypertension. 8. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (&#8804;6 months), myocardial infarction (&#8804; 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. 9. Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes. 10. Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration. |
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E.5 End points |
E.5.1 | Primary end point(s) |
This is a phase I-II study. At each dose level (first step) will be treated a cohort of 3 consecutive patients. In absence of dose- limiting toxicity (DLT) we will proceed to the next dose-level. Each cycle of treatment will be repeated every three weeks and patients are scheduled to receive at least three courses of therapy at the same dose level. Escalation of the dose to the next higher level proceeds after all 3 patients received the first cycle of therapy with the preceding dose and have been observed for at least 21 days without evidence of a dose-limiting toxicity (DLT), as defined below. Drug-related toxicities will be evaluated during each cycle of therapy and graded according to the NCI Common Toxicity Criteria. A DLT is defined as any of the following events: grade 4 neutropenia, grade 4 thrombocytopenia; any drug-related nonhematological toxicity greater than or equal to grade 3 (except alopecia). At the occurrence of a DLT in three patients from any cohort, an additional three patients will be enrolled at the preceding dose level, which is then considered the maximum tolerated dose (MTD) and the recommended dose for further evaluation (second step). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |