A Study of MM-121 in Combination With Paclitaxel in Patients With Advanced Gynecologic and Breast Cancers

September 6, 2016 updated by: Merrimack Pharmaceuticals

A Phase 1, Pharmacologic and Pharmacodynamic Study of MM-121 in Combination With Paclitaxel in Patients With Advanced Gynecologic and Breast Cancers

This study was a Phase 1 and pharmacologic open-labeled dose-escalation trial of MM-121 in combination with paclitaxel using a "3+3" design.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Successive cohorts of three or more patients were treated at escalating doses until a maximum tolerated dose/recommended phase 1 dose was identified. Once the maximum tolerated dose was identified, an Expansion Cohort was enrolled at that dose to further characterize safety and to explore pharmacodynamic endpoints.

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham Comprehensive Cancer Center
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Pinnacle Oncology Hematology
    • California
      • Bakersfield, California, United States, 93309
        • Comprehensive Blood And Cancer Center
      • Fresno, California, United States, 93720
        • Cancer Care Associates of Fresno
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Cytological or histological confirmation of locally advanced/metastatic or recurrent epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer or endometrial cancer; OR, cytological or histological confirmation of locally advanced /metastatic Her2 non-overexpressing breast cancer
  • Eighteen years of age or above
  • Candidates for chemotherapy
  • Able to understand and sign an informed consent (or have a legal representative who is able to do so)
  • Measurable disease according to RECIST v1.1
  • ECOG Performance Score (PS) of ≤ 2
  • Willing to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-121

Exclusion Criteria:

  • Prior radiation therapy to >25% of bone marrow-bearing areas
  • Evidence of any other active malignancy
  • Active infection or fever> 38.5°C during screening visits or on the first scheduled day of dosing
  • Symptomatic CNS disease
  • Known hypersensitivity to any of the components of MM-121 or who have had hypersensitivity reactions to fully human monoclonal antibodies
  • Received treatment, within 30 days prior to the first scheduled day of dosing, with any investigational agents that have not received regulatory approval for any indication or disease state
  • Pregnant or breast feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MM-121 + Paclitaxel
Escalating doses of MM-121 given IV QW in combination with paclitaxel at standard dose of 80 mg/m2 IV QW
Drug: MM-121
increasing doses of MM-121 IV QW
Other Names:
  • Seribantumab, SAR256212
Drug: Paclitaxel
Paclitaxel - 80 mg/m2 IV QW
Other Names:
  • Taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation: To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Plus Paclitaxel Combination Via Reporting of Dose-limiting Toxicity (DLT)
Time Frame: From date of first dose to 30 days after termination, the longest 163 weeks
To establish the safety of escalating doses of MM-121 in combination with paclitaxel in order to determine the recommended phase 2 dose. 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.
From date of first dose to 30 days after termination, the longest 163 weeks
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: MM-121 Dose Level
Time Frame: From date of first dose to 30 days after termination, the longest 163 weeks

Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort.

Part 1 Cohort 1: MM-121: 20 mg/kg loading dose followed by 12 mg/kg QW IV )20/12) + Paclitaxel: 80mg/m2 IV QW Part 1 Cohort 2: MM-121: 40 mg/kg loading dose followed by 20 mg/kg QW IV (40/20) + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 1: MM-121: 40/20 mg/kg IV + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 2: MM-121 20 /12 mg/kg IV QW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 3: MM-121 40mg/kg IV QOW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 4: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest + Paclitaxel: 80mg/m2 weekly IV for 3 weeks, followed by one week of rest
From date of first dose to 30 days after termination, the longest 163 weeks
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: Paclitaxel Dose Level
Time Frame: From date of first dose to 30 days after termination, the longest 163 weeks

Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort.

Part 1 Cohort 1: MM-121: 20 mg/kg loading dose followed by 12 mg/kg QW IV )20/12) + Paclitaxel: 80mg/m2 IV QW Part 1 Cohort 2: MM-121: 40 mg/kg loading dose followed by 20 mg/kg QW IV (40/20) + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 1: MM-121: 40/20 mg/kg IV + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 2: MM-121 20 /12 mg/kg IV QW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 3: MM-121 40mg/kg IV QOW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 4: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest + Paclitaxel: 80mg/m2 weekly IV for 3 weeks, followed by one week of rest
From date of first dose to 30 days after termination, the longest 163 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To Characterize the Efficacy of the Combination of MM-121 and Paclitaxel Using Objective Response Rate
Time Frame: patients were assessed for response during their time on study, the longest of which was 163 weeks
To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response (PR) is defined as >20% decrease in tumor burden from baseline and a Complete Response (CR) is defined as complete disappearance from tumor burden from baseline. Objective Response is presented as the total # patients with PR or CR.
patients were assessed for response during their time on study, the longest of which was 163 weeks
To Determine the Pharmacokinetics (PK) of MM-121 When Administered in Combination With Paclitaxel
Time Frame: Collections taken at for all patients at Cycle 1, Week 1 (pre-treatment/pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121) and pre-treatment at Cycle 1, Week 3 and Cycle 2, Week 1
Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the maximum observed concentration (Cmax). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (20/12 mg/kg weekly, 40/20 mg/kg weekly, 40 mg/kg Q2W, or 40/20 mg/kg QW x 7 plus a rest week).
Collections taken at for all patients at Cycle 1, Week 1 (pre-treatment/pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121) and pre-treatment at Cycle 1, Week 3 and Cycle 2, Week 1
Pharmacokinetic Parameters (AUClast)
Time Frame: Collections taken at for all patients at Cycle 1, Week 1 (pre-treatment/pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121) and pre-treatment at Cycle 1, Week 3 and Cycle 2, Week 1

Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the maximum observed concentration (Cmax). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (20/12 mg/kg weekly, 40/20 mg/kg weekly, 40 mg/kg Q2W, or 40/20 mg/kg QW x 7 plus a rest week).

Immunogenicity data is not available.
Collections taken at for all patients at Cycle 1, Week 1 (pre-treatment/pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121) and pre-treatment at Cycle 1, Week 3 and Cycle 2, Week 1
Immunogenicity
Time Frame: Samples were collected for all patients pre-dose on all cycles for duration of treatment, the longest of which was 163 weeks, and a collection was made post-infusion in any case of infusion reaction
Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies).
Samples were collected for all patients pre-dose on all cycles for duration of treatment, the longest of which was 163 weeks, and a collection was made post-infusion in any case of infusion reaction

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merrimack Pharmaceuticals

Collaborators

Sanofi

Investigators

  • Study Director: Akos Czibere, MD, PhD, Merrimack Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

September 23, 2010

First Submitted That Met QC Criteria

September 23, 2010

First Posted (Estimate)

September 27, 2010

Study Record Updates

Last Update Posted (Estimate)

September 8, 2016

Last Update Submitted That Met QC Criteria

September 6, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MM-121-04-01-04

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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