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

NCT00928330 | Completed Phase 1

• 2 other identifiers: GDC4627gGO01302
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 3

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.

Conditions

Metastatic Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Changes in cardiac function

  Through study completion or early study discontinuation

• 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

  Through study completion or early study discontinuation

• Incidence, nature, and severity of adverse events

  Through study completion or early study discontinuation

Secondary Outcomes (4)

• PK parameters of T-DM1 and GDC-0941 (total exposure, maximum serum concentration, and minimum concentration)

  Through study completion or early study discontinuation

• Progression-free survival (PFS)

  From study treatment initiation to the first occurrence of disease progression or death on study

• Objective response based on investigator assessment

  Confirmed response >/= 4 weeks after initial documentation of response

• Duration of response

  Time from initial complete or partial response to the time of disease progression or death on study

Study Arms (3)

A

EXPERIMENTAL

Drug: GDC-0941; Drug: trastuzumab-MCC-DM1

B

EXPERIMENTAL

Drug: GDC-0941; Drug: trastuzumab-MCC-DM1

C

EXPERIMENTAL

Drug: GDC-0941; Drug: Trastuzumab

Interventions

GDC-0941 DRUG

Oral repeating dose

A; B; C

Trastuzumab DRUG

Intravenous repeating dose

C

trastuzumab-MCC-DM1 DRUG

Intravenous repeating dose

A; B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (3)

Unknown Facility

Indianapolis, Indiana, 46202, United States

Location

Unknown Facility

Baltimore, Maryland, 21231, United States

Location

Unknown Facility

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine; Trastuzumab; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2009
• First Posted: June 25, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

US (3)