Clinical Trials/NCT02658084

NCT02658084

Terminated

Phase 1

A Phase I/II Study to Evaluate the Safety and Efficacy of Vinorelbine With Trastuzumab Emtansine in Pre-Treated HER2-Positive Metastatic Breast Cancer

University of Miami1 site in 1 country2 target enrollmentApril 12, 2017

ConditionsBreast Cancer Metastatic Breast Cancer

InterventionsVinorelbine Trastuzumab Emtansine

DrugsVinorelbine Trastuzumab Emtansine

Overview

Phase: Phase 1
Intervention: Vinorelbine
Conditions: Breast Cancer
Sponsor: University of Miami
Enrollment: 2
Locations: 1
Primary Endpoint: Phase 2 - Rate of Progression-Free Survival (PFS)
Status: Terminated
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The study proposes to evaluate the safety and efficacy of the combination of trastuzumab emtansine (T-DM1) and vinorelbine in HER2+ metastatic breast cancer patients.

Detailed Description

This is a Phase I/II, single arm, open-label clinical trial designed to establish the recommended phase II dose (RP2D) of vinorelbine with a fixed dose of trastuzumab emtansine. The study will also evaluate the safety and efficacy of the RP2D in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic, locally advanced, or unresectable breast cancer. The study will be opened to accrual at the University of Miami Sylvester Comprehensive Cancer Center (SCCC) main campus and constituent satellite sites, Deerfield Beach and Plantation. This phase I/II study will have a total of 50 enrolled patients, taking into account 10% drop-out in the phase II follow-up. The duration anticipated to enroll all study subjects in Phase I/II is 2 years. The estimated duration for the Investigators to complete this study (Phase I/II) is 4.5 to 5 years. For the phase I portion, standard 3+3 dose escalation/de-escalation design will be applied. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D). For the phase II portion of the study, up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I. Patients may remain on treatment with the combination until disease progression or unmanageable toxicity. Tumor assessments will be conducted every 6 weeks (±7 days) to week 18. Thereafter, these assessments will be done every 12 weeks (±7 days). These will shall occur regardless of dose delays or dose interruptions, until Investigator-assessed progressive disease (PD), or death, whichever occurs first. More frequent tumor assessments may be performed as clinically indicated, at the discretion of the treating Investigator. For the phase II portion of the study - patients who discontinue treatment for reasons other than PD will continue to have required tumor assessments completed until PD or the initiation of a new therapy. Once patients have progressed, they will be followed for survival approximately every 3 months for at least 3 years. Subsequent anti-cancer therapies will be documented until study completion. Patients who are discontinued from study treatment will return for the Study Treatment Discontinuation Visit approximately 30 days (±7 days) after the last dose of study treatment.

Registry

clinicaltrials.gov

Start Date

April 12, 2017

End Date

October 11, 2018

Last Updated

7 years ago

Study Type

Interventional

Study Design

Crossover

Sex

Female

Investigators

Sponsor

University of Miami

Responsible Party

Principal Investigator

Reshma Mahtani

Assistant Professor of Clinical

University of Miami

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically documented breast cancer.
•Metastatic or unresectable locally advanced/recurrent breast cancer.
•HER2-positive disease documented as: Immunohistochemistry (IHC) 3+ positive, and/or Fluorescence in situ hybridization (FISH) ≥ 2.0, and/or gene copy number greater than 6, on previously collected tumor or metastatic site. IHC testing, FISH assay(s), and gene copy number may all have been performed; however, a positive result from only one of the above is required for eligibility.
•Documented disease progression on the last regimen by radiographic measurement (progression demonstrated by tumor markers only is unacceptable).
•Documented disease progression (by investigator assessment) after at least one regimen of HER2-directed therapy in the metastatic or unresectable locally advanced/recurrent setting.
•For patients with hormone receptor-positive disease: disease progression or recurrence in any setting on prior hormonal therapy, given with or without HER2 directed therapy.
•Measurable or bone only disease.
•Prior treatment with a taxane, in the neoadjuvant, adjuvant, locally advanced or metastatic setting.
•A minimum of 6 weeks of prior trastuzumab for the treatment of metastatic or unresectable locally advanced/recurrent disease is required.
•Prior use of Pertuzumab in any setting is permitted (but not required).

Exclusion Criteria

•Chemotherapy ≤21 days prior to first dose of study treatment
•If last dose of trastuzumab was:
•6mg/kg then ≤21 days prior to first dose of study treatment
•4mg/kg then ≤14 days prior to first dose of study treatment
•2mg/kg then ≤7 days prior to first dose of study treatment
•Lapatinib ≤14 days prior to first dose of study treatment
•Pertuzumab ≤21 days prior to first dose of study treatment
•Hormone therapy ≤7 days prior to first dose of study treatment
•Investigational therapy or any other such experimental therapy ≤28 days prior to first dose of study treatment
•Prior treatment with trastuzumab emtansine, (on or off a study protocol)

Arms & Interventions

Phase 1: T-DM1 + Vinorelbine

One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).

Intervention: Vinorelbine

Phase 1: T-DM1 + Vinorelbine

Intervention: Trastuzumab Emtansine

Phase 2: T-DM1 + RP2D Vinorelbine

One cycle of trastuzumab emtansine (T-DM1)/vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). Participants will receive the recommended Phase 2 Dose (RPSD) of Vinorelbine with the fixed dose (3.6 mg/kg) of Trastuzumab Emtansine. Participants will be treated until documented disease progression or other criteria for discontinuation. Up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I.

Intervention: Vinorelbine

Phase 2: T-DM1 + RP2D Vinorelbine

Intervention: Trastuzumab Emtansine

Outcomes

Primary Outcomes

Phase 2 - Rate of Progression-Free Survival (PFS)

Time Frame: Up to 5 years

Rate of Progression-Free Survival (PFS) in participants receiving the RP2D of vinorelbine in combination with Trastuzumab Emtansine therapy. PFS is defined as the time from date from first treatment received on study until documented disease progression or death (by any cause, in the absence of progression). In progression-free patients, PFS will be censored at the last evaluable tumor assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

Phase 1 - Maximum Tolerated Dose (MTD) of Vinorelbine in Combination With a Fixed Dose of Trastuzumab Emtansine.

Time Frame: 2 years

Identifying the Maximum Tolerated Dose (MTD) of Vinorelbine combined with a fixed dose of Trastuzumab Emtansine to be recommended for the phase II portion of the study (RP2D).

Phase 1 - Rate of Participants Experiencing Adverse Events

Time Frame: 18 months

Rate of participants experiencing adverse events including dose-limiting toxicities (DLTs) and serious adverse events (SAEs).