Phase Ib/II study of efficacy and safety of MEK162 pluspanitumumab in adult metastatic colorectal cancer patients with mutant or wild-typeRAS tumors

Phase 1

• Conditions: Mutant RAS or wild-type (WT) RAS metastatic colorectal cancer; MedDRA version: 18.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: HLTClassification code 10010023Term: Colorectal neoplasms malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10010030Term: Colorectal cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-001986-18-FR
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-17
• Last Update Posted: 4 July 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Age = 18 years
2. Histological or cytological confirmation of mCRC
3. For the dose escalation (Phase Ib): Progression on or following standard therapy or for whom no standard therapy exists. See protocol for complete details
4. Phase Ib and Phase II: Written documentation of WT RAS or somatic mutation in exon 2 (codons 12/13), 3 (codons 59/61) or 4 (codons 117/146) in either KRAS or NRAS in medical history.
5. Evidence of measurable disease, as determined by RECIST v1.1.
6. Life expectancy = 3 months.
Other protocol-defined inclusion criteria may apply
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 59
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion Criteria

1.Phase II arms 1 and 4 only: previous treatment with cetuximab, panitumumab, and/or other EGFR inhibitors. For arms 2 and 3: EGFR tyrosine kinase inhibitor therapy.
2.Previous treatment with MEK-inhibitors - certain exceptions. See protocol
3.Patients with known history of severe infusion reactions to monoclonal antibodies.
4.Known hypersensitivity and/or contraindication to any of the study medications or their excipients
5.Symptomatic or untreated leptomeningeal disease.
6.Symptomatic brain metastasis.
7.History or current evidence of retinal disease or ophthalmopathy
8.History of keratitis or ulcerative keratitis.
9.Known acute or chronic pancreatitis.
10.Clinically significant cardiac disease - see protocol
12.Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral MEK162
13.Previous or concurrent malignancy - with exceptions - see protocol
14.History of thromboembolic or cerebrovascular events within the last 6 months
15.Patients who have received radiation therapy , chemotherapy, biological therapy within = 4 weeks or who have been treated with continuous or intermittent small molecule therapeutics or investigational agents within 5 half-lives of the agent - See protocol
16.Patients who have undergone any major surgery within the last 2 weeks prior to starting study drug or who would not have fully recovered from previous surgery.
17.Known human immunodeficiency virus (HIV) infection.
18.Pregnant or nursing (lactating) women
Other protocol-defined exclusion criteria may apply

Study & Design

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