A Combination Study of Kadcyla (Trastuzumab Emtansine) and Capecitabine in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (mBC) or HER2-Positive Locally Advanced/Metastatic Gastric Cancer (LA/mGC) (TRAXHER2)

Roche

Status and phase: Terminated; Phase 2

Conditions: Breast Cancer; Gastric Cancer

Treatments: Drug: Capecitabine; Drug: Trastuzumab emtansine (T-DM1)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01702558

MO28230

2012-001547-46 (EudraCT Number)

Details and patient eligibility

About

This multicenter study will assess the maximum tolerated dose (MTD) of capecitabine in combination with Kadcyla (trastuzumab emtansine) in participants with HER2-positive mBC or HER2-positive LA/mGC using a Phase 1 design, followed by a randomized, open-label Phase 2 part to explore the efficacy and safety of the combination of Kadcyla and capecitabine compared with Kadcyla alone in participants with mBC. The anticipated time on study treatment is until disease progression, intolerable toxicity, withdrawal of consent, or study end.

Enrollment: 182 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Metastatic Breast Cancer

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Adequate blood cell count
• Adequate liver, renal, and cardiac function
• Life expectancy greater than or equal to (>/=) 12 weeks
• Histologically or cytologically confirmed breast cancer
• Confirmed HER2-positive disease, defined as immunohistochemistry (IHC) 3+ or in situ hybridization (ISH)-positive
• mBC with at least one measurable lesion according to RECIST v1.1
• Disease progression on at least one prior regimen containing trastuzumab and chemotherapy either separately or in combination; participants may be eligible to receive study therapy in first-line setting if trastuzumab and chemotherapy were given in the neoadjuvant/adjuvant setting
• Participant must have recovered from previous treatments

Locally Advanced/Metastatic Gastric Cancer

• ECOG performance status of 0, 1, or 2
• Adequate blood cell count
• Adequate liver, renal, and cardiac function
• Life expectancy >/= 12 weeks
• Histologically or cytologically confirmed LA/mGC
• HER2-positive tumor (primary tumor or metastatic lesion), defined as either IHC 3+ or IHC 2+ and ISH-positive
• Inoperable LA/mGC

Exclusion criteria

Metastatic Breast Cancer

• Prior treatments before first study treatment:

  1. Investigational therapy within 28 days or 5 half-lives, whichever is longer
  2. Hormonal therapy within 14 days
  3. Trastuzumab within 21 days

• Prior treatment with trastuzumab emtansine or prior enrollment in a trastuzumab emtansine-containing study, regardless of whether the patient received trastuzumab emtansine

• Prior treatment with capecitabine

• History of severe or unexpected reactions to fluoropyrimidine or known hypersensitivity to fluorouracil

• Related capecitabine contraindications

  1. Treatment with sorivudine or chemically-related analogues
  2. Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
  3. Complete absence of dihydropyrimidine dehydrogenase (DPD) activity

• History of intolerance or hypersensitivity to trastuzumab or murine proteins or any product component

• History of exposure to high cumulative doses of anthracyclines

• Brain metastases that are symptomatic or require radiation, surgery, or steroid therapy to control symptoms within 28 days before study drug

• Current peripheral neuropathy of Grade >/=3

• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome

• Current unstable ventricular arrhythmia requiring treatment

• History of symptomatic congestive heart failure (CHF)

• History of myocardial infarction or unstable angina within 6 months prior to study drug

• History of left ventricular ejection fraction (LVEF) less than (<) 40% or symptomatic CHF with previous trastuzumab treatment

• Severe dyspnea at rest due to complications of advanced malignancy or currently requiring continuous oxygen therapy

• Clinically significant malabsorption syndrome or inability to take oral medication

• Current severe, uncontrolled systemic disease (such as clinically significant cardiovascular, pulmonary, or metabolic disease)

• Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during study treatment

• Current known active infection with human immunodeficiency virus (HIV) or hepatitis B or C

• Lapatinib within 14 days before study drug

Locally Advanced/Metastatic Gastric Cancer

• Same as above, with addition of previous chemotherapy for advanced/metastatic disease (prior adjuvant/neoadjuvant therapy is allowed if at least 6 months has elapsed between completion of adjuvant/neoadjuvant therapy and enrollment into the study)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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182 participants in 4 patient groups

Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine

Experimental group

Description:

In Phase 1, Cohort 1 participants (with mBC) will receive trastuzumab emtansine (T-DM1) at a dose of 3.6 milligrams per kilogram (mg/kg) via intravenous (IV) infusion (on Day 1 \[on Day 2 for Cycle 1\] of each 21-day cycle) along with capecitabine at de-escalating dose levels (starting from 750 milligrams per meter squared \[mg/m\^2\]) via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, disease progression (PD), death, or study end.

Treatment:

Drug: Trastuzumab emtansine (T-DM1)

Drug: Trastuzumab emtansine (T-DM1)

Drug: Capecitabine

Drug: Capecitabine

Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine

Experimental group

Description:

In Phase 1, Cohort 2 participants (with LA/mGC) will receive trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (on Day 2 of first week) of every week along with capecitabine at MTD (determined in Cohort 1) via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end.

Treatment:

Drug: Trastuzumab emtansine (T-DM1)

Drug: Trastuzumab emtansine (T-DM1)

Drug: Capecitabine

Drug: Capecitabine

Phase 2 (mBC): T-DM1 + Capecitabine

Active Comparator group

Description:

In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at MTD via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end.

Treatment:

Drug: Trastuzumab emtansine (T-DM1)

Drug: Trastuzumab emtansine (T-DM1)

Drug: Capecitabine

Drug: Capecitabine

Phase 2 (mBC): T-DM1

Experimental group

Description:

In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, or study end.

Treatment:

Drug: Trastuzumab emtansine (T-DM1)

Drug: Trastuzumab emtansine (T-DM1)