| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| LOCALLY-ADVANCED OR METASTATIC COLORECTAL CANCER |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10052362 |
| E.1.2 | Term | Metastatic colorectal cancer |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010035 |
| E.1.2 | Term | Colorectal cancer stage IV |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010034 |
| E.1.2 | Term | Colorectal cancer stage III |
|
| 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 |
| The primary objective of this study is to evaluate the anti-tumor activity (best overall response rate [ORR]) of the anti-EGFR monoclonal antibody IMC-11F8 administered in combination with the mFOLFOX-6 chemotherapy regimen in treatment-naïve, locally-advanced or metastatic colorectal cancer patients. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate:
• the overall survival
• the progression-free survival
• the safety profile
• the duration of response
• the pharmacokinetic profile of IMC-11F8 and immunogenicity of IMC-11F8
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. The patient must have histologically-confirmed, EGFR-detectable or EGFR-undetectable colorectal cancer. Patients who do not have tissue available for EGFR testing will undergo biopsy of an accessible tumor. A waiver may be given to patients who do not wish to undergo a biopsy.
2. The patient has locally-advanced unresectable or metastatic adenocarcinoma of the colon or rectum.
3. The patient has at least one unidimensionally-measurable target lesion (≥2 cm with conventional techniques or ≥1 cm with spiral computed tomography [CT] scan) by CT scan or magnetic resonance imaging (MRI); target lesion(s) must not lie within an irradiated area.
4. The patient is age ≥18 years.
5. The patient has a life expectancy of ≥6 months.
6. The patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) <2 at study entry.
7. The patient has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1.5 x 109/L, hemoglobin ≥10 g/dL (the patient may be transfused or may be receiving erythropoietin to meet this criterion), and platelets ≥100 x 109/L.
8. The patient has adequate hepatic function as defined by a total bilirubin ≤1.5 mg/dL, aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 X upper limit of normal (ULN) [or 5.0 x ULN in the case of liver metastases], and alkaline phosphatase ≤2.5 x ULN (or 5.0 x ULN in the case of liver metastases).
9. The patient has adequate renal function as defined by a serum creatinine 1.5 x ULN, creatinine clearance (measured or calculated) ≥60 mL/min, or serum albumin ≥ lower limit of normal institutional range (LLN).
10. The patient’s relevant toxicities/effects of prior therapy (surgery, radiotherapy) must have recovered to a stable or chronic (grade 1) level.
11. The patient agrees to use adequate contraception during the study period and for 4 weeks after the last dose of study treatment. Patients must notify the principal investigator if they themselves or their partner becomes pregnant.
12. The patient has provided signed informed consent.
|
|
| E.4 | Principal exclusion criteria |
1. The patient has received prior systemic chemotherapy for locally-advanced unresectable or metastatic CRC. (Prior adjuvant chemotherapy is allowed if disease progression has been documented (including serum tumor markers, if available) >6 months after the end of the last cycle of adjuvant chemotherapy or ≥12 months for oxaliplatin-containing regimens.)
2. The patient has received prior radiotherapy to >25% of bone marrow. (Radiation therapy as a part of standard adjuvant chemoradiotherapy for rectal cancer >6 months prior to study entry is allowed.)
3. The patient has documented and/or symptomatic brain metastases.
4. The patient has participated in clinical studies of non-approved experimental agents or procedures within 12 weeks of study entry.
5. The patient has received previous therapy with monoclonal antibodies.
6. The patient has received previous therapy with any agent that targets the epidermal growth factor receptor.
7. The patient has serious concomitant medical conditions including active uncontrolled infection or cardiac disease, which in the opinion of the investigator, could compromise the patient or the study.
8. The patient is on chronic non-topical corticosteroid treatment for >6 months at doses >10 mg/day of prednisolone or equivalent before study entry, which in the opinion of the investigator could compromise the patient or the study.
9. The patient has a known dihydropyrimidine dehydrogenase (DPD) deficiency.
10. The patient has a known allergy to any of the treatment components.
11. The patient has an acute or subacute intestinal occlusion.
12. The patient has peripheral neuropathy ≥ grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE], Version 3.0).
13. The patient has a history of other malignancies, with the exception of curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix.
14. The patient, if female, is pregnant (confirmed by urine or serum beta human chorionic gonadotropin [βHCG] test) or breast-feeding.
15. The patient has received a prior autologous or allogeneic organ or tissue transplantation.
16. The patient has interstitial pneumonia or interstitial fibrosis of the lung.
17. The patient has pleural effusion or ascites that causes ≥ grade 2 dyspnea.
18. The patient has psychological, familial, sociological, or geographical conditions which do not permit adequate study follow-up, compliance with the protocol, or signature of Informed Consent.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Endpoint:
Best overall response rate (ORR: CR + PR) as determined according to RECIST. An overall response will be evaluated for each patient every four cycles. Responses must be confirmed at least 4 weeks after the criteria for response were first met.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| 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 | Yes |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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