E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This study will enroll patients with untreated, metastatic colorectal carcinoma who are eligible for first line FOLFOX therapy. |
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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 | 10052358 |
E.1.2 | Term | Colorectal 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 |
The objective of this Phase II study is to evaluate the safety, tolerability and efficacy of FOLFOX plus CT-011 versus FOLFOX alone administered intravenously to patients with colorectal adenocarcinoma previously untreated for metastatic disease. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of CT -011 Evaluate the pharmacokinetics and immunogenicity of CT-011 Evaluate the progression - free survival rate Evaluate the overall survival Evaluate th eobiective response rate by RECIST Evaluate of duration of response Evaluate the serum levelsof the tumor marker CEA Evaluate the imune reactivity by: - profiles of lymphocyte sub populations Periferal blood lymphocyte cell surface markers |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patient’s age is 18 years or older, both genders. 2) Histologically or cytologically confirmed adenocarcinoma of the colon or rectum 3) Patients with metastatic disease who are eligible for first line FOLFOX chemotherapy. Adjuvant or neoadjuvant given at least 12 months prior for non-metastatic disease is permited. 4) Measurable disease defined by the identification at least 1 measurable lesion by CT scan using RECIST criteria. MRI with contrast may be in use in situations where CT scan results are inconsistent with respect to the extent of the disease in the liver. PET scan is not to be used to assess measurability or response. 5) ECOG performance status ≤ 1 6) Serum albumin greater than 3.5 7) At least 4 weeks from prior major surgery or radiotherapy. 8) Life expectancy >3 months 9) Hematology: ANC ≥ 1.5X109/L; Platelets >100x109/L. 10) Adequate Renal function Creatinine <1.5 x the upper limit of normal (ULN) or calculated creatinine clearance of ≥ 50cc/min. 11) Adequate Hepatic functions: Bilirubin less than 1.5 mg/dL; (except in patients with Gilbert’s Syndrome, who must have a total bilirubin less than 3.0 mg/dL). AST or ALT <3xULN, or <5x ULN if known liver metastases. 12) Normal Cardiac function: No active coronary artery disease; No New York Heart Association class II, III or IV disease; no arrhythmia requiring treatment. 13) Women with child bearing potential who are negative for pregnancy test (urine or blood) and who agree to use effective contraceptive method. Reliable contraception should be used from trial screening and must be continued throughout the study and until at least four months from the last CT-011 treatment. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. 14) A man participating in this study must agree to utilize reliable barrier form of contraception for the duration of the study and during 4 months from the last CT-011 treatment. 15) Signed and dated written informed consent to participate in this clinical trial must be obtained prior to any study procedure. |
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E.4 | Principal exclusion criteria |
1) Patients who had adjuvant or neoadjuvant therapy for non-metastatic disease given within the last 12 months. 2) Patients who had received Oxaliplatin within 12 months prior to diagnosis of metastatic disease. 3) Patients on concurrent anti cancer therapy other than that allowed in the study. 4) Patients on concurrent steroids, other than those allowed for routine antiemetics, or inhaled steroids 5) Presence of clinically apparent or suspected brain metastasis. 6) Patients who have had myocardial infarction, severe congestive heart failure, or significant arrhythmia within the past 6 months. 7) Serious active infection at the time of pre-study screening. Conditions requiring antibiotics must be fully resolved off of antibiotics before initiating treatment on protocol. 8) Active or history of autoimmune disorders/conditions including ulcerative colitis or active diverticulitis. Chronic Diabetes meletis, vitiligo or stable hypothyroidism will not be considered exclusion criteria. 9) Women who are pregnant or lactating 10) Concurrent active malignancy. 11) Ascites, pleural effusions, or osteoblastic bone metastases as the only site of disease. 12) Other prior malignancies, except for cured non melanoma skin cancer or curatively treated in situ carcinoma of the cervix or adequately treated malignancies for which there has been no evidence of activity for more than 5 years. 13) Subjects with a condition which may interfere with the subjects' ability to understand the requirements of the study. 14) Patients with history of life threatening allergic reactions to food or drugs 15) Patients with symptomatic peripheral neuropathy> Grade 1. 16) Known positive HIV, Hepatitis B surface antigen or Hepatitis C antibody. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is the median progression free survival in patients with colorectal adenocarcinoma previously untreated for metastatic disease treated with CT-011 in combination with FOLFOX compared to that of patients treated with FOLFOX alone. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
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) | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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The end of the trial is the last visit by the last patient. The study will be early terminated only by the data monitoring committee due to safety concerns. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |