E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 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 |
This study is divided into 2 parts: a phase 1b portion (part 1) and a phase 2 portion (part 2).
Part 1: The primary objective of part 1 is to identify a tolerable dose of AMG 655 in combination with panitumumab based on the incidence of dose-limiting toxicities (DLTs) in subjects with metastatic colorectal cancer (mCRC).
Part 2: The primary objective of part 2 is to evaluate stratified by KRAS status (wild-type versus mutant) the objective response rate (ORR) in subjects with mCRC treated with the combination of panitumumab and AMG 655 (tolerable dose identified in part 1). |
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E.2.2 | Secondary objectives of the trial |
Secondary Part 1 and 2: To evaluate the effect of the combination of panitumumab and AMG 655 overall and stratified by KRAS status (wild-type versus mutant) on the following secondary endpoints in subjects with mCRC: • Incidence of all adverse events (AEs) and clinical laboratory abnormalities • Incidence of human anti-panitumumab antibodies (HAPA) and human anti-AMG 655 antibodies • Objective response (OR) • Duration of response • Time to response • Disease control rate (includes complete response [CR] and partial response [PR], or stable disease [SD]) • Progression-free survival (PFS) • Overall survival (OS) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria
Disease Related - Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum - Radiographically documented disease progression per modified RECIST during or following treatment with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for mCRC. Progressive disease must be documented during or ≤ 6 months after the last dose of the most recent chemotherapy regimen prior to enrollment - At least 1 uni-dimensionally measurable lesion measuring ≥ 20 mm in one dimension per modified RECIST (Appendix D). Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Available archived paraffin-embedded tumor tissue from the primary tumor or metastasis for submission to the central laboratory (see Section 7.7)
Demographic - Man or woman ≥ 18 years of age at the time of enrollment
Laboratory (performed ≤ 7 days before enrollment) - Hematologic function within the following limits: - Absolute neutrophil count (ANC) > 1.0 x 109 cells/L - Platelets ≥ 100 x 109/L - Renal function within the following limits: - Creatinine < 2.0 mg/dL - Hepatic function within the following limits: - Aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases) - Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases) - Bilirubin ≤ 2 x ULN - Metabolic function within the following limits: - Amylase ≤ 2 x ULN - Lipase ≤ 2 x ULN - Magnesium ≥ lower limit of normal - Negative pregnancy test ≤ 72 hours before enrollment (for woman of childbearing potential only)
Medications - Subject must have received 1, 2, or 3 prior chemotherapy regimens for mCRC
Ethical - Competent to comprehend, sign, and date the IEC/IRB approved written informed consent |
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E.4 | Principal exclusion criteria |
Disease Related - History of other primary cancer, unless: - Curatively resected non-melanomatous skin cancer - Curatively treated cervical carcinoma in situ - Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before enrollment
Medications - Prior treatment with anti-EGFr inhibitors (eg, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting ≥ 6 months before enrollment - Use of systemic chemotherapy and radiotherapy ≤ 30 days before enrollment - Use of prior anti-tumor therapies with a short serum half-life (less than 1 week) including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrollment - Use of anti-tumor therapies with a longer serum half-life (eg, bevacizumab) including prior experimental or approved protein/antibodies ≤ 42 days before enrollment - Any investigational agent or therapy ≤ 30 days before enrollment - Known allergy or hypersensitivity to any component of panitumumab and/or AMG 655
General - History of or known presence of central nervous system (CNS) metastases - History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan - Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment - Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ CTC grade 2 [CTCAE version 3.0]) - Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection - Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion) - Any uncontrolled concurrent illness (eg, infection, bleeding) or history of any medical condition that may interfere with the interpretation of the study results - Major surgical procedure (requiring general anesthesia) ≤ 28 days or minor surgical procedure (excluding central venous catheter placement) ≤ 14 days before enrollment. Subjects must have recovered from surgery related toxicities. - Other investigational procedures are excluded - Subject is currently pregnant or breast feeding - Man or woman of childbearing potential who is not willing to use adequate contraceptive precautions during treatment and for 6 months (for women) or 1 month (for men) after the last investigational product administration. Adequate contraceptive precautions includes double barrier contraceptive methods (eg, diaphragm and condom) or abstinence. - Previously enrolled into this study - Subject unwilling or unable to comply with study requirements |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1 - Dose-limiting Toxicity (DLT): Incidence of selected adverse events and laboratory abnormalities as defined in Section 6.6 of the Protocol.
Part 2 - Overall Objective Response (OR): The incidence during the treatment phase of either a confirmed CR or PR per modified RECIST criteria (responder). A confirmed CR requires 2 assessments of CR at least 28 days apart. A confirmed PR requires 2 assessments at least 28 days apart of PR or CR. All subjects that do not meet the criteria for an objective response by the analysis cutoff date will be considered nonresponders. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
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 | 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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
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 | 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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The end of study for each subject is defined as the date the subject withdraws consent from the study, completes the final long-term follow-up visit, or death. This has been estimated to be no more than 2 years after the last subject is enrolled into the study. |
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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 | |
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 |