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

NCT01209195 | Completed Phase 1 Results

• 1 other identifier: MM-121-04-01-04
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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

  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

  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 Outcomes (4)

• To Characterize the Efficacy of the Combination of MM-121 and Paclitaxel Using Objective Response Rate

  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

  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)

  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

  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

Study Arms (1)

MM-121 + Paclitaxel

EXPERIMENTAL

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

Drug: MM-121; Drug: Paclitaxel

Interventions

MM-121 DRUG

increasing doses of MM-121 IV QW

Also known as: Seribantumab, SAR256212

MM-121 + Paclitaxel

Paclitaxel DRUG

Paclitaxel - 80 mg/m2 IV QW

Also known as: Taxol

MM-121 + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merrimack Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (5)

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Pinnacle Oncology Hematology

Scottsdale, Arizona, 85258, United States

Location

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

Cancer Care Associates of Fresno

Fresno, California, 93720, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Ovarian Neoplasms; Fallopian Tube Neoplasms; Endometrial Neoplasms; Breast Neoplasms

Interventions

seribantumab; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Uterine Neoplasms; Uterine Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Clinical Trial Manager
• Organization: Merrimack Pharmaceuticals, Inc.

smathews@merrimack.com

617-441-1000

Study Officials

• Akos Czibere, MD, PhD

  Merrimack Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2010
• First Posted: September 27, 2010
• Study Start: October 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: July 1, 2014
• Last Updated: September 8, 2016
• Results First Posted: September 8, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)