A Study of MM-121 Combination Therapy in Patients With Advanced Non-Small Cell Lung Cancer

Phase 1

Completed

• Conditions: Carcinoma, Non-Small-Cell Lung
• Interventions: Drug: MM-121; Drug: Erlotinib

• Registration Number: NCT00994123
• Lead Sponsor: Merrimack Pharmaceuticals

Brief Summary

A Phase 1-2 study of MM-121 in combination with standard therapy for non-small cell lung cancer (NSCLC).

Detailed Description

Phase 1: Patients with Non-Small Cell Lung Cancer (NSCLC) may be enrolled to evaluate the safety, tolerability and recommended Phase 2 dose of MM-121 in combination with standard therapy.

Phase 2: Patients with Non-Small Cell Lung Cancer (NSCLC) may be enrolled to estimate the progression-free survival of the MM-121 + standard therapy.

Study Timeline

• Study First Submitted: 2009-10-13
• Study First Submitted QC: 2009-10-13
• Study First Posted: 2009-10-14
• Study Start: 2010-02
• Primary Completion: 2014-11
• Study Completion: 2015-06
• Results First Submitted: 2016-02-14
• Status Verified: 2016-07
• Results First Submitted QC: 2016-07-12
• Last Update Submitted: 2016-07-12
• Results First Posted: 2016-08-22
• Last Update Posted: 2016-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 162

Inclusion Criteria

• Patients with locally advanced or metastatic non-small cell lung cancer.
• Patients must be >/= 18 years of age.
• Patients must have adequate Performance Status (PS) as measured by ECOG and adequate end organ function.

Exclusion Criteria

• Patients with a recent history (within 5 years) of another malignancy.
• Patients who are pregnant or nursing.
• Patients with clinically significant heart failure.
• Patients with clinically significant eye or gastrointestinal abnormalities.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2: Treatment	Erlotinib	MM-121 (QOW IV) and erlotinib (daily PO)
Phase 1: Dose-Escalation	Erlotinib	Escalating doses of MM-121 (QOW IV) and erlotinib (daily PO)
Phase 2: Control	Erlotinib	Erlotinib (daily)
Phase 2: Treatment	MM-121	MM-121 (QOW IV) and erlotinib (daily PO)
Phase 1: Dose-Escalation	MM-121	Escalating doses of MM-121 (QOW IV) and erlotinib (daily PO)

Primary Outcome Measures

Name	Time	Method
Phase 1: To Determine the Recommended Phase 2 Dose of the MM-121 + Erlotinib Combination Based Upon Either the Maximum Tolerated Dose (MTD) or the Maximum Feasible Dose of the Combination in Patients With NSCLC.	From date of first dose to 30 days after termination, the longest 175 weeks	To establish the safety of escalating doses of MM-121 in combination with erlotinib in order to determine the recommended phase 2 dose of the combination for the second part of the study. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD.
Phase 1: Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities	From date of first dose to 30 days after termination, the longest 175 weeks	Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs.; The determined MTD was used as the recommended Phase 2 dose.
Phase 2: Progression-free Survival of the MM-121 + Erlotinib Combination	Time from first dose to date of progression, with a median of 8.1 weeks	This was a time-to-event measure using Progression-Free Survival (PFS) comparing MM-121 + erlotinib vs.erlotinib alone. Progression of disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions". Progression free survival was defined as the number of weeks from the date of randomization to the date of death or progression. If neither death nor progression was observed during the study, PFS data was censored at the last non-progressive disease valid tumor assessment unless the patient was discontinued due to symptomatic deterioration. If this occurred, the patient was counted as having progressive disease (PD).