Clinical trial NCT01254526: Study of the Safety and Pharmacology of GDC-0980 in Combination With Paclitaxel With or Without Bevacizumab in Patients With Locally Recurrent or Metastatic Breast Cancer
Official title: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0980 in Combination With Paclitaxel With or Without Bevacizumab in Patients With Locally Recurrent or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2010-12-06
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0980 administered with taxane-based chemotherapy regimens utilized in patients with locally recurrent or metastatic breast cancer.


Eligibility criteria: Inclusion Criteria:

* Locally recurrent or metastatic breast cancer, not amenable to resection with curative intent
* For Arm C: Overexpression of HER2
* Eastern Cooperative Oncology Group Performance Status of 0 or 1
* Adequate hematologic and organ function
* Evaluable or measurable disease per RECIST (Response Evaluable Criteria in Solid Tumors)
* Female patients of childbearing potential must use an acceptable method of contraception to prevent pregnancy and to continue its use for the duration of the study

Exclusion Criteria:

* Prior anti-cancer therapy of more than two regimens of systemic cytotoxic chemotherapy for advanced or metastatic breast cancer
* Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, or hormonal therapy) within a specified timeframe of the first dose of study treatment
* History of Type 1 or Type 2 diabetes requiring regular medication
* History of clinically significant cardiac or pulmonary dysfunction
* History of malabsorption syndrome or other condition that would interfere with enteral absorption
* Any condition requiring full-dose anticoagulants
* Leptomeningeal disease as a manifestation of cancer
* Active infection requiring IV antibiotics
* Active autoimmune disease that is not controlled by non-steroidal anti-inflammatory drugs, inhaled steroids, or the equivalent of \<= 10 mg/day of prednisone
* Known clinically significant history of liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
* Known HIV infection
* Known untreated or active CNS metastases
* Pregnancy, lactation, or breastfeeding
* Major surgical procedure, open biopsy, or significant traumatic injury within a within a specified timeframe of the first dose of study treatment

For Arm B:

* Uncontrolled hypertension, complication from hypertension, myocardial infarctions, unstable angina, vascular disease or stroke within a specified timeframe of the first dose of study treatment
* Evidence of bleeding diathesis or significant coagulopathy including hemoptysis within a specified timeframe of the first dose of study treatment
* History of abdominal conditions (e.g., fistula, perforation, obstruction) that would preclude use of bevacizumab
* Serious, non-healing wound, active ulcer, or untreated bone fracture
* Proteinuria

Primary outcomes:
measure: Incidence and nature of dose-limiting toxicities (DLTs)
timeFrame: Through Day 22
measure: Incidence, nature, and severity of adverse events
timeFrame: Through study completion, up to 1 year, or early discontinuation
Secondary outcomes:
measure: Pharmacokinetic parameters of GDC-0980, paclitaxel and bevacizumab (including total exposure, maximum and minimum plasma concentration, time to maximum observed plasma concentration, plasma half-life)
timeFrame: Through Day 22
measure: Duration of response
timeFrame: Assessed at periodic intervals until study completion, up to 1 year, or early discontinuation
measure: Progression-free survival (PFS)
timeFrame: Assessed at periodic intervals until study completion, up to 1 year, or early discontinuation
measure: Objective tumor response
timeFrame: Assessed at periodic intervals until study completion, up to 1 year, or early discontinuation
Other outcomes:
Locations:
city: Boston
country: United States
state: Massachusetts
city: Nashville
country: United States
state: Tennessee
city: Leuven
country: Belgium
Study officials:
affiliation: Genentech, Inc.
name: Jennifer Lauchle, M.D.
role: STUDY_DIRECTOR
References: