Trastuzumab and Trastuzumab-MCC-DM1 Administered Intravenously and GDC-0941 Administered Orally to Patients With HER2-Positive Metastatic Breast Cancer Who Have Progressed on Previous Trastuzumab-Based Therapy

• ClinicalTrials.gov Identifier: NCT00928330
• Recruitment Status: Completed
• First Posted: June 25, 2009
• Last Update Posted: November 2, 2016
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Study Description

Brief Summary:

This multicenter, Phase Ib study is an open label, dose escalation, three-arm study evaluating the safety, tolerability, pharmacokinetics, and activity of oral (PO) GDC 0941 administered in combination with either intravenous (IV) infusion of T-DM1 or IV infusion of trastuzumab.

Condition or disease	Intervention/treatment	Phase
Metastatic Breast Cancer	Drug: GDC-0941; Drug: Trastuzumab; Drug: trastuzumab-MCC-DM1	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, and Activity of Trastuzumab and Trastuzumab-MCC-DM1 Administered Intravenously and GDC-0941 Administered Orally to Patients With HER2-Positive Metastatic Breast Cancer Who Have Progressed on Previous Trastuzumab-Based Therapy
• Study Start Date: July 2009
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: A	Drug: GDC-0941; Oral repeating dose; Drug: trastuzumab-MCC-DM1; Intravenous repeating dose
Experimental: B	Drug: GDC-0941; Oral repeating dose; Drug: trastuzumab-MCC-DM1; Intravenous repeating dose
Experimental: C	Drug: GDC-0941; Oral repeating dose; Drug: Trastuzumab; Intravenous repeating dose

Outcome Measures

Primary Outcome Measures :

1. Changes in cardiac function [ Time Frame: Through study completion or early study discontinuation ]
2. Changes in vital signs, physical findings, and clinical laboratory results during and following administration of study drugs that result in dose modification, dose delay, or discontinuation of T-DM1 and/or GDC 0941 [ Time Frame: Through study completion or early study discontinuation ]
3. Incidence, nature, and severity of adverse events [ Time Frame: Through study completion or early study discontinuation ]

Secondary Outcome Measures :

1. PK parameters of T-DM1 and GDC-0941 (total exposure, maximum serum concentration, and minimum concentration) [ Time Frame: Through study completion or early study discontinuation ]
2. Progression-free survival (PFS) [ Time Frame: From study treatment initiation to the first occurrence of disease progression or death on study ]
3. Objective response based on investigator assessment [ Time Frame: Confirmed response >/= 4 weeks after initial documentation of response ]
4. Duration of response [ Time Frame: Time from initial complete or partial response to the time of disease progression or death on study ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically documented locally advanced or metastatic breast cancer that has progressed on at least one trastuzumab-based regimen in the metastatic or locally advanced setting
• HER2-positive disease documented by one of the following results using FDA-approved testing methods: FISH-positive, chromogenic in situ hybridization (CISH)-positive, or IHC 3 + by local laboratory assessment
• Life expectancy >= 90 days
• Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria:

• History of Grade >= 3 hypersensitivity reaction to trastuzumab, or Grade >= 1 with the most recent trastuzumab infusion before study entry, or continued requirement for prolonged trastuzumab infusions to prevent hypersensitivity reactions
• History of intolerance to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued
• Prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy, hormonal therapy) within 2 weeks prior to Day 1
• Prior investigational anti-cancer therapy within 4 weeks prior to Day 1
• Grade >= 2 peripheral neuropathy
• History of Grade >= 3 hyperglycemia (fasting)
• History of Type 1 or Type 2 diabetes requiring daily medication
• History of clinically significant cardiac or pulmonary dysfunction
• History of malabsorption syndrome or other condition that would interfere with enteral absorption
• Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C virus
• Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytic agents
• Any condition requiring > 2 grams of acetaminophen daily
• Need for current chronic corticosteroid therapy
• Pregnancy, lactation, or breast-feeding
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
• Major surgical procedure or significant traumatic injury within 28 days prior to Day 1, or anticipation of the need for major surgery during the course of study treatment
• Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms

Contacts and Locations

Locations

United States, Indiana

Indianapolis, Indiana, United States, 46202

United States, Maryland

Baltimore, Maryland, United States, 21231

United States, Massachusetts

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Genentech, Inc.

Investigators

• Study Director: Clinical Trials; Genentech, Inc.

More Information

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT00928330
• Other Study ID Numbers: GDC4627g; GO01302 ( Other Identifier: Hoffmann-La Roche )
• First Posted: June 25, 2009
• Last Update Posted: November 2, 2016
• Last Verified: November 2016

Keywords provided by Genentech, Inc.:

TDM-1; HER2; HER2+; HER2+ Breast Cancer; HER-2; MBC; Trastuzumab emtansine

Additional relevant MeSH terms:

Ado-Trastuzumab Emtansine; Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Trastuzumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunotoxins; Immunoconjugates; Immunologic Factors; Physiological Effects of Drugs; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action