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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00928330
• Other study ID #: GDC4627g
• Secondary ID: GO01302
• Status: Completed
• Phase: Phase 1
• First received: June 23, 2009
• Last updated: November 1, 2016
• Start date: July 2009
• Est. completion date: January 2014

Study information

• Verified date: November 2016
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• GDC-0941
Oral repeating dose
• Trastuzumab
Intravenous repeating dose
• trastuzumab-MCC-DM1
Intravenous repeating 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	Changes in cardiac function		Through study completion or early study discontinuation	No
Primary	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	No
Primary	Incidence, nature, and severity of adverse events		Through study completion or early study discontinuation	No
Secondary	PK parameters of T-DM1 and GDC-0941 (total exposure, maximum serum concentration, and minimum concentration)		Through study completion or early study discontinuation	No
Secondary	Progression-free survival (PFS)		From study treatment initiation to the first occurrence of disease progression or death on study	No
Secondary	Objective response based on investigator assessment		Confirmed response >/= 4 weeks after initial documentation of response	No
Secondary	Duration of response		Time from initial complete or partial response to the time of disease progression or death on study	No