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

• ClinicalTrials.gov Identifier: NCT00994123
• Recruitment Status: Completed
• First Posted: October 14, 2009
• Results First Posted: August 22, 2016
• Last Update Posted: August 22, 2016
• Sponsor: Merrimack Pharmaceuticals
• Information provided by (Responsible Party): Merrimack Pharmaceuticals

Tracking Information

• First Submitted Date: October 13, 2009
• First Posted Date: October 14, 2009
• Results First Submitted Date: February 14, 2016
• Results First Posted Date: August 22, 2016
• Last Update Posted Date: August 22, 2016
• Study Start Date: February 2010
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 12, 2016)

• 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. [ Time Frame: 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 [ Time Frame: 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 Frame: 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).

• Original Primary Outcome Measures (submitted: October 13, 2009): 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. [ Time Frame: December 2009 ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures (submitted: October 13, 2009): Phase 2: To estimate the Non-Progression Rate of the MM-121 + erlotinib combination at >/= 24 weeks in patients with NSCLC. [ Time Frame: January 2011 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of MM-121 Combination Therapy in Patients With Advanced Non-Small Cell Lung Cancer
• Official Title: A Phase 1-2 Trial of MM-121 in Combination With Erlotinib in Three Groups of Patients With Non-Small Cell Lung Cancer
• 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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• Drug: MM-121
  MM-121 (SAR256212) = intravenous solution
  Other Name: SAR256212
• Drug: Erlotinib
  erlotinib = daily oral tablet
  Other Name: Tarceva

Study Arms

• Experimental: Phase 1: Dose-Escalation
  Escalating doses of MM-121 (QOW IV) and erlotinib (daily PO)
  Interventions:

  • Drug: MM-121
  • Drug: Erlotinib
• Active Comparator: Phase 2: Control
  Erlotinib (daily)
  Intervention: Drug: Erlotinib
• Experimental: Phase 2: Treatment
  MM-121 (QOW IV) and erlotinib (daily PO)
  Interventions:

  • Drug: MM-121
  • Drug: Erlotinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 12, 2016): 162
• Original Estimated Enrollment (submitted: October 13, 2009): 40
• Actual Study Completion Date: June 2015
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, Korea, Republic of, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT00994123
• Other Study ID Numbers: MM-121-01-101
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Merrimack Pharmaceuticals
• Study Sponsor: Merrimack Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Victor Moyo, MD; Merrimack Pharmaceuticals

• PRS Account: Merrimack Pharmaceuticals
• Verification Date: July 2016