E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Second-Line Treatment for Metastatic Colorectal Cancer. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061045 |
|
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 the study is to compare the PFS of subjects with metastatic CRC when treated with CT-322 (BMS-844203) in combination with FOLFIRI chemotherapy versus bevacizumab in combination with FOLFIRI. |
|
E.2.2 | Secondary objectives of the trial |
To compare overall survival (OS) between the 2 treatment arms To compare the objective tumor response rate (ORR) between the 2 treatment arms To estimate the duration of response and time to response in each of the 2 treatment arms To evaluate the safety of CT-322 (BMS-844203) plus FOLFIRI To evaluate the pharmacokinetics of CT-322 (BMS-844203) when administered in combination with irinotecan/SN-38, 5-FU and leucovorin. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOCINETICA/FARMACODINAMICA: Versione:1.0 Data:2009/02/05 Titolo:sottostudio PK (farmacocinetica) Obiettivi:A circa 12 pazienti per ogni gruppo di trattamento verranno raccolti I campioni per misurare la concentrazione plasmatica di CT-322 (BMS-844203). Riferimento nella sezione 6.5 del protocollo.
ALTRI SOTTOSTUDI: Sottostudio FDG-PET :Riferimento nella sezione 6.4.2.1 del protocollo.
|
|
E.3 | Principal inclusion criteria |
1) Signed Written Informed Consent 2) Target Population a) Histologically or cytologically confirmed, unresectable, metastatic adenocarcinoma of the colon or rectum that has progressed following first-line treatment which included each of the following agents: i) A fluoropyrimidine (5-FU or capecitabine) ii) Oxaliplatin (Subjects who are intolerant to oxaliplatin, defined as any toxicity preventing treatment with oxaliplatin, are permitted if disease progression has been documented following discontinuation of oxaliplatin) iii) Bevacizumab (last dose of bevacizumab must be < 8 weeks from the start of study therapy). b) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) &#8804; 1 c) Resolution of all prior therapy-related toxicities to &#8804; Grade 1 or baseline d) Measurable disease as defined by RECIST criteria (at least 1 target lesion &#8805; 20 mm by conventional techniques, or &#8805; 10 mm by spiral CT) i) If the only measurable disease is located in a previously radiated area, lesions must be documented as new lesions since the completion of radiotherapy. 3) Age and Sex a) Men and women of &#8805; 18 years of age. b) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study (and for up to 4 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized. |
|
E.4 | Principal exclusion criteria |
1) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study [and for up to 4 weeks after the last dose of investigational product]. b) Women who are pregnant or breastfeeding c) Women with a positive pregnancy test on enrollment or prior to investigational product administration. d) Sexually active fertile men not using effective birth control if their partners are WOCBP. 2) Target Disease Exceptions a) Known Central Nervous System (CNS) metastases. 3) Medical History and Concurrent Diseases a) Excessive risk of bleeding such as history of clinically significant bleeding diathesis or coagulopathy including platelet function disorder or acquired bleeding disorder within 12 months. b) Thrombotic or embolic cerebrovascular accident including transient ischemic attacks within the past 12 months. c) Uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg or diastolic > 90 mmHg, measured repeatedly at &#8805; 2 visits despite adequate treatment with &#8805; 2 different antihypertensive drugs). d) Clinically significant cardiovascular disease, including (but not limited to) the following: i) Myocardial infarction within the past 6 months ii) Unstable angina iii) New York Heart Association class II-IV congestive heart failure iv) Serious cardiac arrhythmia (eg, ventricular arrhythmia, high-grade atrioventricular-block), not controlled by medication or requiring medication which might interfere with regularity of study treatment. v) Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) as measured by 2-dimensional echocardiogram (ECHO) or cardiac MUGA scan. e) History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months. f) Serious non-healing wound, active peptic ulcer, non-healing bone fracture, or bleeding skin metastases. g) Active infection requiring IV antibiotics. h) Glomerulonephritis or other protein-wasting glomerulopathy. i) Gilberts disease. j) Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in-situ of the cervix. k) Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. l) A serious uncontrolled medical disorder that, in the opinion of the investigator, would impair the ability of the subject to receive study therapy. 4) Physical and Laboratory Test Findings a) Hematology: i) Hemoglobin < 9.0 g/dL, Absolute Neutrophil Count < 1500 /mm3, Platelets < 100,000 /mm3 b) Chemistry: i) Serum creatinine > 1.5 times the institutional upper limit of normal (ULN) ii) Serum total bilirubin > 1.5 times ULN iii) ALT or AST > 2.5 times ULN (> 5 times ULN for subjects with documented liver metastases). iv) Serum amylase and lipase > 1.5 times ULN. c) Known UGT1A1*28 allele homozygosity. 5) Allergies and Adverse Drug Reactions a) Known hypersensitivity to any of the study drugs or excipients. 6) Prohibited Treatments and/or Therapies a) Any prior treatment with irinotecan, including treatment in the adjuvant setting. b) Any prior treatment with VEGF or VEGFR inhibitors, with the exception of bevacizumab. FOR A COMPLETE LIST PLEASE REFER TO THE PROTOCOL. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is PFS and is based on tumor assessments (CT scans/MRI) that will be performed every 6 weeks until documented PD, death or initiation of subsequent therapy for CRC. Safety will be evaluated weekly for all treated subjects. Additional assessments include: metabolic response based on FDG-PET, pharmacokinetic, pharmacodynamics, pharmacogenomic/pharmacogenetic and immunogenicity assessments. |
|
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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
|
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
|
The study will end once all subjects have completed follow-up for toxicity and PD, or when 80% of death events have occurred, whichever comes last. |
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |