Comparison of survival benefit of panitumumab with supportive care to best supportive care alone in patients with metastatic colorectal cancer

Phase 1

• Conditions: Chemorefractory, Wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS), Metastatic Colorectal Cancer; MedDRA version: 13.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-022951-49-GR
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05-17
• Last Update Posted: 12 December 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

4.1.1 Disease Related
• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum
- Metastatic disease
• Wild-type (without mutation in codons 12 and 13) KRAS gene in tumor tissue confirmed by a central laboratory (see Section 7.2)
- KRAS mutational analysis may have been performed by the central
laboratory prior to obtaining consent for study
- Formalin-fixed paraffin-embedded tumor tissue from either the primary tumor or a metastatic lesion must be available and submitted to Amgen approved central laboratory for KRAS testing and/or other biomarker testing
• ECOG performance status of 0, 1 or 2
• At least 1 measurable or non-measurable lesion per RECIST version 1.1 guidelines. Lesion must not be chosen from a previously irradiated field unless there had been documented tumor progression in that lesion prior to randomization. All sites of disease must be evaluated = 28 days prior to randomization
• Treatment failure (defined as failure due to either disease progression [clinical or radiological] or toxicity [treatment intolerance]) of a prior regimen containing irinotecan for metastatic disease and a prior regimen containing oxaliplatin for metastatic disease. Oxaliplatin and irinotecan may have been administered sequentially or in combination.
- Disease relapse within 6 months after completing adjuvant chemotherapy (with either an irinotecan or oxaliplatin containing regimen) will also be considered as treatment failure of a prior regimen for metastatic disease
• Must have previously received a thymidylate synthase inhibitor (eg, fluorouracil, capecitabine, raltitrexed, or fluorouracil-uracil) at any point for treatment of CRC
4.1.2 Demographic
• Man or woman = 18 years of age
4.1.3 Laboratory
• Hematologic function, as follows: (= 10 days prior to randomization)
- Absolute neutrophil count (ANC) = 1.5 x 109/L
- Platelet count = 75 x 109/L
- Hemoglobin = 8.0 g/dL
• Renal function, as follows: (= 10 days prior to randomization)
- Creatinine = 1.5 x ULN
• Hepatic function, as follows: (= 10 days prior to randomization)
- Aspartate aminotransferase (AST) = 3 x ULN (if liver metastases = 5 x ULN)
- Alanine aminotransferase (ALT) = 3 x ULN (if liver metastases = 5 x ULN)
- Total bilirubin = 1.5 x ULN
• Metabolic function, as follows: (= 10 days prior to randomization)
- Magnesium = lower limit of normal
• Negative pregnancy test = 72 hours before randomization (for women of childbearing potential only)
4.1.4 Ethical
• Subject or subject’s legally acceptable
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 228
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 122

Exclusion Criteria

4.2.1 Disease Related
• Symptomatic brain metastases requiring treatment
• History of other malignancy, except:
- Malignancy treated with curative intent and with no known active disease present for = 5 years prior to randomization and felt to be at low risk for recurrence by the treating physician
- Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer
4.2.2 Medications
• Prior anti-EGFR antibody therapy (eg, panitumumab or cetuximab) or treatment with small molecule EGFR inhibitors (eg, gefitinib, erlotinib, lapatinib)
• Antitumor therapy (eg, chemotherapy, hormonal therapy, immunotherapy, antibody therapy) = 21 days before randomization. Subjects must have recovered from any acute toxicity
• Radiotherapy = 14 days before randomization. Subjects must have recovered from any acute radiotherapy-related toxicities
4.2.3 General
• Subject previously randomized to this study
• Other investigational procedures = 30 days before randomization
• Subject currently enrolled in or = 30 days from ending other investigational device or drug study(s)
• Major surgery (eg, requiring general anesthesia) = 28 days before randomization. Subjects must have recovered from any surgery related toxicities
• Minor surgical procedure (eg, open biopsy) = 7 days before randomization, or not yet recovered from prior minor surgery
Note:uncomplicated placement of vascular access device, fine needle aspiration, thoracocentesis or paracentesis = 3 days prior to randomization is acceptable
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) = 6 months prior to randomization
• History of interstitial lung disease (ILD) eg, interstitial pneumonitis, pulmonary fibrosis or evidence of ILD on baseline chest CT or MRI
• History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with the study participation or investigational product administration or may interfere with the interpretation of the results
• Unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic event = 30 days before randomization. If on anticoagulation, subject must be on stable therapeutic dose prior to randomization.
• Subject pregnant or breast feeding, or planning to become pregnant during treatment and within 2 months after the end of treatment
• Female subject of childbearing potential is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for at least an additional 2 months after the end of treatment
• Known positive test(s) for human immunodeficiency virus infection (testing is not required in the absence of clinical suspicion)
• Active infection requiring systemic treatment or any uncontrolled infection = 14 days prior to randomization (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection)
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures or is unwilling or unable to comply with study requirements
4.2.4 Exclusion Criteria for QT

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified