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

Metastatic Breast Cancer Clinical Trial

Official title:

A Phase Ib-IIa, Open-label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of Trastuzumab Emtansine, Paclitaxel and Pertuzumab Administered Intravenously to Patients With Her2-positive, Locally Advanced or Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00951665
• Other study ID #: TDM4652g
• Secondary ID: GO01355
• Status: Completed
• Phase: Phase 1
• First received: August 3, 2009
• Last updated: October 1, 2015
• Start date: August 2009
• Est. completion date: June 2013

Study information

• Verified date: October 2015
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 HER2-positive, locally advanced or metastatic breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: June 2013
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 trastuzumab emtansine (T-DM1) or pertuzumab therapy

• Measurable or evaluable disease

• Cardiac ejection fraction >=50% by either ECHO or MUGA 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

Study Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• paclitaxel
Intravenous repeating dose
• pertuzumab [Perjeta]
Intravenous repeating dose
• trastuzumab emtansine [Kadcyla]
Intravenous escalating dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events or changes in physical findings and clinical laboratory results during and following study drug administration that result in dose modification, dose delay, or discontinuation of trastuzumab emtansine, paclitaxel, and/or pertuzumab		Through study discontinuation or 12 months of study treatment, whichever occurs first	No
Primary	Frequency and nature of dose limiting toxicities (DLTs) and highest tolerable doses of trastuzumab emtansine and paclitaxel when given in combination		Through study discontinuation or 12 months of study treatment, whichever occurs first	No
Primary	Incidence, nature, and severity of adverse events and serious adverse events		Through study discontinuation or 12 months of study treatment, whichever occurs first	No
Primary	Pharmacokinetics of trastuzumab emtansine in the presence of paclitaxel, and of paclitaxel in the presence and absence of trastuzumab emtansine		Through study discontinuation or 12 months of study treatment, whichever occurs first	No
Primary	Phase IIa: Proportion of patients who receive paclitaxel weekly x 12 doses in combination with trastuzumab emtansine (with or without pertuzumab)		Through study discontinuation or 12 months of study treatment, whichever occurs first	No
Secondary	Objective response rate based on investigator assessment		Through study discontinuation or 12 months of study treatment, whichever occurs first	No
Secondary	Progression-free survival, duration of response and clinical benefit rate		Through study discontinuation or 12 months of study treatment, whichever occurs first	No