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Completed

NCT Number: NCT01209195

A 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.

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Key information

Conditions

Locally Advanced/Metastatic or Recurrent Ovarian Cancer, Fallopian Tube Cancer, Adnexal Diseases Breast Diseases Breast Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Neoplasms Fallopian Tube Diseases Fallopian Tube Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Locally Advanced/Metastatic Her2 Non Overexpressing Breast Cancer Neoplasm Metastasis Neoplasms Neoplasms by Site Neoplastic Processes Ovarian Diseases Ovarian Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Primary Peritoneal Cancer or Endometrial Cancer Skin Diseases Skin and Connective Tissue Diseases Urogenital Diseases Urogenital Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

MM-121

Drug

increasing doses of MM-121 IV QW

Other names: Seribantumab, SAR256212

paclitaxel

Drug

Paclitaxel - 80 mg/m2 IV QW

Other names: Taxol

Primary outcomes

  1. 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.

  2. 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

  3. 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

Secondary outcomes

  1. 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.

  2. 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).

  3. 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.

  4. 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).

Sponsors and collaborators

Lead sponsor

Merrimack Pharmaceuticals

Industry

Collaborators

  • Sanofi

Registry information

Official study title

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

Important dates

Study start
2010
Primary completion
2014
Study completion
2014
First posted
Sep 27, 2010
Registry last updated
Sep 8, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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