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

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Roche

Status and phase

Completed
Phase 2
Phase 1

Conditions

Metastatic Breast Cancer

Treatments

Drug: Trastuzumab emtansine [Kadcyla] 3.0 mg/kg
Drug: Pertuzumab 420 mg
Drug: Trastuzumab emtansine [Kadcyla] 3.6 mg/kg

Study type

Interventional

Funder types

Industry

Identifiers

NCT00875979
TDM4373g (Other Identifier)
BO22495

Details and patient eligibility

About

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.

Full 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.

Enrollment

67 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

67 participants in 2 patient groups

Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg
Experimental group
Description:
Patients received trastuzumab emtansine 3.0 mg/kg intravenously (IV) on Day 1 of every 3 week cycle until progressive disease, intolerable toxicity, initiation of another anti-cancer therapy, or patient discontinuation. Patients also received a loading dose of 840 mg of pertuzumab IV on Day 1 of Cycle 1 followed by pertuzumab 420 mg IV on Day 1 of every subsequent 3 week cycle.
Treatment:
Drug: Pertuzumab 420 mg
Drug: Trastuzumab emtansine [Kadcyla] 3.0 mg/kg
Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg
Experimental group
Description:
Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) on Day 1 of every 3 week cycle until progressive disease, intolerable toxicity, initiation of another anti-cancer therapy, or patient discontinuation. Patients also received a loading dose of 840 mg of pertuzumab IV on Day 1 of Cycle 1 followed by pertuzumab 420 mg IV on Day 1 of every subsequent 3 week cycle.
Treatment:
Drug: Trastuzumab emtansine [Kadcyla] 3.6 mg/kg
Drug: Pertuzumab 420 mg

Trial contacts and locations

20

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Data sourced from clinicaltrials.gov

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