Vinorelbine With Trastuzumab Emtansine in Pre-Treated HER2-Positive Metastatic Breast Cancer

NCT02658084 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 20151055
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Metastatic Breast Cancer

Keywords

HER2-Positive; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (3)

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

  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).

  2 years

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

  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.

  Up to 5 years

• Phase 1 - Rate of Participants Experiencing Adverse Events

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

  18 months

Secondary Outcomes (3)

• Phase 2 - Clinical Benefit Rate (CBR)

  Up to 5 years

• Phase 2 - Overall Survival (OS) Rate

  Up to 5 Years

• Phase 2 - Objective Response Rate (ORR)

  Up to 5 Years

Study Arms (2)

Phase 1: T-DM1 + Vinorelbine

EXPERIMENTAL

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).

Drug: Vinorelbine; Drug: Trastuzumab Emtansine

Phase 2: T-DM1 + RP2D Vinorelbine

EXPERIMENTAL

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.

Drug: Vinorelbine; Drug: Trastuzumab Emtansine

Interventions

Vinorelbine DRUG

Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Also known as: Vinorelbine tartrate, Navelbine

Phase 1: T-DM1 + Vinorelbine; Phase 2: T-DM1 + RP2D Vinorelbine

Trastuzumab Emtansine DRUG

Administered as an intravenous infusion on Day 1 of every 21-day cycle.

Also known as: Kadcyla, T-DM1, Trastuzumab-MCC-DM1

Phase 1: T-DM1 + Vinorelbine; Phase 2: T-DM1 + RP2D Vinorelbine

Eligibility Criteria

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

You may qualify if:

• 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).
• Prior use of Lapatinib in any setting is permitted (but not required).
• Age ≥ 18 years
• Life expectancy ≥ 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. See Appendix C for details.
• Patients must have normal organ and marrow function as defined below:

You may not qualify if:

• Chemotherapy ≤21 days prior to first dose of study treatment
• If last dose of trastuzumab was:
• mg/kg then ≤21 days prior to first dose of study treatment
• mg/kg then ≤14 days prior to first dose of study treatment
• mg/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)
• Prior use of vinorelbine (in any setting).
• Previous radiotherapy for the treatment of unresectable, locally advanced, recurrent or metastatic breast cancer is not allowed if:
• The last fraction of radiotherapy has been administered within 14 days prior to study enrollment
• More than 25% of marrow-bearing bone has been irradiated
• Brain metastases that are untreated or symptomatic, or require any radiation, surgery, or continued steroid therapy to control symptoms from brain metastases within 14 days of study enrollment.

Sponsors & Collaborators

• University of Miami: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Vinorelbine; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Early study termination by mutual decision of the Sponsor and the Investigator due to lower than expected accrual and toxicities concerns. Only the Phase 1 arm opened to accrual; Phase 2 did not open to accrual.

Results Point of Contact

• Title: Dr. Reshma Mahtani
• Organization: University of Miami

rmahtani@miami.edu

954-698-3639

Study Officials

• Reshma Mahtani, DO

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: January 18, 2016
• Study Start: April 12, 2017
• Primary Completion: October 11, 2018
• Study Completion: October 11, 2018
• Last Updated: April 17, 2019
• Results First Posted: April 17, 2019

Record last verified: 2019-04

Locations

US (1)