search
Back to results

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

Primary Purpose

Locally Advanced/Metastatic or Recurrent Ovarian Cancer, Fallopian Tube Cancer,, Primary Peritoneal Cancer or Endometrial Cancer, Locally Advanced/Metastatic Her2 Non Overexpressing Breast Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MM-121
Paclitaxel
Sponsored by
Merrimack Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced/Metastatic or Recurrent Ovarian Cancer, Fallopian Tube Cancer, focused on measuring Ovarian cancer, HER-2 negative breast cancer, Breast cancer, Fallopian tube cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham Comprehensive Cancer Center
  • Pinnacle Oncology Hematology
  • Comprehensive Blood and Cancer Center
  • Cancer Care Associates of Fresno
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MM-121 + Paclitaxel

Arm Description

Escalating doses of MM-121 given IV QW in combination with paclitaxel at standard dose of 80 mg/m2 IV QW

Outcomes

Primary Outcome Measures

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)
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.
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: MM-121 Dose Level
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
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: Paclitaxel Dose Level
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

Secondary Outcome Measures

To Characterize the Efficacy of the Combination of MM-121 and Paclitaxel Using Objective Response Rate
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.
To Determine the Pharmacokinetics (PK) of MM-121 When Administered in Combination With Paclitaxel
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).
Pharmacokinetic Parameters (AUClast)
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.
Immunogenicity
Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies).

Full Information

First Posted
September 23, 2010
Last Updated
September 6, 2016
Sponsor
Merrimack Pharmaceuticals
Collaborators
Sanofi
search

1. Study Identification

Unique Protocol Identification Number
NCT01209195
Brief Title
A Study of MM-121 in Combination With Paclitaxel in Patients With Advanced Gynecologic and Breast Cancers
Official Title
A Phase 1, Pharmacologic and Pharmacodynamic Study of MM-121 in Combination With Paclitaxel in Patients With Advanced Gynecologic and Breast Cancers
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merrimack Pharmaceuticals
Collaborators
Sanofi

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced/Metastatic or Recurrent Ovarian Cancer, Fallopian Tube Cancer,, Primary Peritoneal Cancer or Endometrial Cancer, Locally Advanced/Metastatic Her2 Non Overexpressing Breast Cancer
Keywords
Ovarian cancer, HER-2 negative breast cancer, Breast cancer, Fallopian tube cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MM-121 + Paclitaxel
Arm Type
Experimental
Arm Description
Escalating doses of MM-121 given IV QW in combination with paclitaxel at standard dose of 80 mg/m2 IV QW
Intervention Type
Drug
Intervention Name(s)
MM-121
Other Intervention Name(s)
Seribantumab, SAR256212
Intervention Description
increasing doses of MM-121 IV QW
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxol
Intervention Description
Paclitaxel - 80 mg/m2 IV QW
Primary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
From date of first dose to 30 days after termination, the longest 163 weeks
Title
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: MM-121 Dose Level
Description
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
Time Frame
From date of first dose to 30 days after termination, the longest 163 weeks
Title
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: Paclitaxel Dose Level
Description
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
Time Frame
From date of first dose to 30 days after termination, the longest 163 weeks
Secondary Outcome Measure Information:
Title
To Characterize the Efficacy of the Combination of MM-121 and Paclitaxel Using Objective Response Rate
Description
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.
Time Frame
patients were assessed for response during their time on study, the longest of which was 163 weeks
Title
To Determine the Pharmacokinetics (PK) of MM-121 When Administered in Combination With Paclitaxel
Description
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).
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
Title
Pharmacokinetic Parameters (AUClast)
Description
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.
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
Title
Immunogenicity
Description
Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies).
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Akos Czibere, MD, PhD
Organizational Affiliation
Merrimack Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Pinnacle Oncology Hematology
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Comprehensive Blood and Cancer Center
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
Facility Name
Cancer Care Associates of Fresno
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs