A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT00951665

Last Updated: 2016-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2013-06-30

Brief Summary

This Phase Ib-IIa, multi-institutional, open-label, dose-escalation study is designed to evaluate the safety, tolerability, pharmacokinetics and feasibility of trastuzumab emtansine (T-DM1) administered by intravenous (IV) infusion in combination with paclitaxel (and pertuzumab, if applicable) in patients with human epidermal growth factor receptor 2-positive (HER2-positive), locally advanced or metastatic breast cancer.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase lb Regimen 1

Participants received trastuzumab emtansine (T-DM1) every three weeks (Q3W) + paclitaxel weekly (QW) intravenously.

Group Type: EXPERIMENTAL

trastuzumab emtansine [Kadcyla]

Intervention Type: DRUG

Intravenous escalating dose

paclitaxel

Intervention Type: DRUG

Intravenous escalating dose

Phase Ib Regimen 2

Participants received T-DM1 Q3W + paclitaxel QW + pertuzumab Q3W intravenously.

Group Type: EXPERIMENTAL

pertuzumab [Perjeta]

Intervention Type: DRUG

Intravenous repeating dose

trastuzumab emtansine [Kadcyla]

Intervention Type: DRUG

Intravenous escalating dose

paclitaxel

Intervention Type: DRUG

Intravenous escalating dose

Phase Ib Regimen 3

Participants received T-DM1 QW + paclitaxel QW intravenously.

Group Type: EXPERIMENTAL

trastuzumab emtansine [Kadcyla]

Intervention Type: DRUG

Intravenous escalating dose

paclitaxel

Intervention Type: DRUG

Intravenous escalating dose

Phase Ib Regimen 4

Participants received T-DM1 QW + paclitaxel QW + pertuzumab Q3W intravenously.

Group Type: EXPERIMENTAL

pertuzumab [Perjeta]

Intervention Type: DRUG

Intravenous repeating dose

trastuzumab emtansine [Kadcyla]

Intervention Type: DRUG

Intravenous escalating dose

paclitaxel

Intervention Type: DRUG

Intravenous escalating dose

Phase IIa Group A

Participants received maximum tolerated dose (MTD) from Phase 1b i.e. T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m\^2 QW intravenously.

Group Type: EXPERIMENTAL

paclitaxel

Intervention Type: DRUG

Intravenous repeating dose

trastuzumab emtansine [Kadcyla]

Intervention Type: DRUG

Intravenous repeating dose

Phase IIa Group B

Participants received MTD from Phase 1b i.e. T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m\^2 QW + pertuzumab Q3W intravenously.

Group Type: EXPERIMENTAL

paclitaxel

Intervention Type: DRUG

Intravenous repeating dose

pertuzumab [Perjeta]

Intervention Type: DRUG

Intravenous repeating dose

trastuzumab emtansine [Kadcyla]

Intervention Type: DRUG

Intravenous repeating dose

Interventions

paclitaxel

Intravenous repeating dose

Intervention Type: DRUG

pertuzumab [Perjeta]

Intravenous repeating dose

Intervention Type: DRUG

trastuzumab emtansine [Kadcyla]

Intravenous escalating dose

Intervention Type: DRUG

paclitaxel

Intravenous escalating dose

Intervention Type: DRUG

trastuzumab emtansine [Kadcyla]

Intravenous repeating dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically documented 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 (Phase Ib patients only)
• No prior T-DM1 or pertuzumab therapy
• Measurable or evaluable disease
• Cardiac ejection fraction >=50% by either echocardiogram or multigated acquisition scan
• Life expectancy >= 90 days as assessed by the investigator

Exclusion Criteria

• Fewer 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 are allowed; palliative radiation therapy involving <=25% of marrow-bearing bone is allowed if completed within >= 14 days prior to first study treatment
• History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab, murine proteins, or any of the excipients that resulted in trastuzumab being permanently discontinued
• Peripheral neuropathy of Grade >= 2 per NCI CTCAE, Version 3.0, at the time of, or within 3 weeks prior to, the first study therapy (Phase Ib patients)
• Peripheral neuropathy of Grade >/=1 per NCI CTCAE, Version 3.0, at the time of, or within 3 weeks prior to, the first study therapy (Phase IIa patients)
• History of exposure to the following cumulative doses of anthracyclines: Doxorubicin > 500 mg/m^2; Liposomal doxorubicin > 900 mg/m^2; Epirubicin > 720 mg/m^2
• History of clinically significant cardiac dysfunction
• Brain metastases that are untreated, or progressive, or have required any type of therapy (including radiation, surgery, or steroids) to control symptoms from brain metastases within 60 days prior to the first study treatment.
• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, basal cell carcinoma, or synchronous or subsequent HER2-positive breast cancer or other malignancy with a similar expected curative outcome

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

Stanford, California, United States

Aurora, Colorado, United States

Boston, Massachusetts, United States

Detroit, Michigan, United States

New York, New York, United States

Countries

United States

References

Krop IE, Modi S, LoRusso PM, Pegram M, Guardino E, Althaus B, Lu D, Strasak A, Elias A. Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer. Breast Cancer Res. 2016 Mar 15;18(1):34. doi: 10.1186/s13058-016-0691-7.

Reference Type: DERIVED

PMID: 26979312 (View on PubMed)

Other Identifiers

GO01355

Identifier Type: OTHER

Identifier Source: secondary_id

TDM4652g

Identifier Type: -

Identifier Source: org_study_id