Clinical trial NCT01209195: 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
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Merrimack Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2010-09-27
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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)
timeFrame: From date of first dose to 30 days after termination, the longest 163 weeks
measure: To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: MM-121 Dose Level
timeFrame: From date of first dose to 30 days after termination, the longest 163 weeks
measure: To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: Paclitaxel Dose Level
timeFrame: From date of first dose to 30 days after termination, the longest 163 weeks
Secondary outcomes:
measure: To Characterize the Efficacy of the Combination of MM-121 and Paclitaxel Using Objective Response Rate
timeFrame: patients were assessed for response during their time on study, the longest of which was 163 weeks
measure: To Determine the Pharmacokinetics (PK) of MM-121 When Administered in Combination With Paclitaxel
timeFrame: 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
measure: Pharmacokinetic Parameters (AUClast)
timeFrame: 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
measure: Immunogenicity
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Scottsdale
country: United States
facility: Pinnacle Oncology Hematology
state: Arizona
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Fresno
country: United States
facility: Cancer Care Associates of Fresno
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Merrimack Pharmaceuticals, Inc.
name: Akos Czibere, MD, PhD
role: STUDY_DIRECTOR
References: