Clinical trial NCT00875979: A Study of Trastuzumab Emtansine (Trastuzumab-MCC-DM1, T-DM1) in Combination With Pertuzumab Administered to Patients With Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer Who Have Previously Received Trastuzumab
Official title: A Phase Ib/II, Open-label Study of the Safety, Tolerability, and Efficacy of Trastuzumab Emtansine (Trastuzumab-MCC-DM1, T-DM1) in Combination With Pertuzumab Administered Intravenously to Patients With Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer Who Have Previously Received Trastuzumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Keywords: MBC
Breast Cancer
HER2+
HER2+ breast cancer
HER2 positive breast cancer
herceptin
Trastuzumab emtansine
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
First posted: 2009-04-06
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a multi-institutional, multinational, open-label, single-arm Phase Ib/II study designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of trastuzumab emtansine (trastuzumab-MCC-DM1) administered by intravenous (IV) infusion in combination with pertuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive locally advanced or metastatic breast cancer who had previously received trastuzumab.

Detailed description: There were 2 phases in the study, a Dose Escalation phase (Phase 1b) and a Dose Expansion phase (Phase 2a). In the Dose Escalation phase, 3 patients were enrolled at the first dose level (3.0 mg/kg trastuzumab emtansine) and and 6 patients were enrolled at the second dose level (3.6 mg/kg trastuzumab emtansine). An additional 58 patients were enrolled at the 3.6 mg/kg trastuzumab emtansine dose level in the Dose Expansion phase (Phase 2a) of the study.

Eligibility criteria: Inclusion Criteria:

* Histologically documented human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer.
* Tumor tissue blocks or 15-20 unstained tissue slides for confirmatory central laboratory HER2 status testing and other exploratory assessments.
* Prior trastuzumab in any line of therapy.
* No prior trastuzumab emtansine (T-DM1) or pertuzumab therapy.
* Measurable disease.
* For women of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of the study.
* Life expectancy ≥ 90 days.

Exclusion Criteria:

* Less than 21 days since the last anti-tumor therapy, including chemotherapy, biologic, experimental, immune, hormonal, or radiotherapy for the treatment of breast cancer, with the following exceptions: Hormone-replacement therapy or oral contraceptives; palliative radiation therapy involving ≤ 25% of marrow-bearing bone if administered ≥ 14 days prior to first study treatment.
* History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued.
* Peripheral neuropathy of Grade ≥ 2.
* History of clinically significant cardiac dysfunction.
* Current severe, uncontrolled systemic disease, eg, clinically significant cardiovascular, pulmonary, or metabolic disease.
* Brain metastases that are untreated, progressive, or have required any type of therapy to control symptoms from brain metastases within 60 days of the first study treatment.
* History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.

Primary outcomes:
measure: Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Baseline through the end of the study (up to 2 years 3 months)
Secondary outcomes:
measure: Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Baseline through the end of the study (up to 2 years 3 months)
measure: Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Baseline through the end of the study (up to 2 years 3 months)
Other outcomes:
Locations:
city: Boca Raton
country: United States
state: Florida
city: Deerfield Beach
country: United States
state: Florida
city: Maywood
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Wichita
country: United States
state: Kansas
city: Rockville
country: United States
state: Maryland
city: Chapel Hill
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Bruxelles
country: Belgium
city: Vancouver
country: Canada
state: British Columbia
city: Montreal
country: Canada
state: Quebec
city: Paris
country: France
city: Villejuif
country: France
city: Köln
country: Germany
city: Aviano
country: Italy
city: Milano
country: Italy
city: Barcelona
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Genentech, Inc.
name: Elaine K. Wong, M.Sc., M.D.
role: STUDY_DIRECTOR
References:
citation: Miller KD, Dieras V, Harbeck N, Andre F, Mahtani RL, Gianni L, Albain KS, Crivellari D, Fang L, Michelson G, de Haas SL, Burris HA. Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer. J Clin Oncol. 2014 May 10;32(14):1437-44. doi: 10.1200/JCO.2013.52.6590. Epub 2014 Apr 14.