GDC-0980 in Combination With a Fluoropyrimidine, Oxaliplatin, and Bevacizumab in Patients With Advanced Solid Tumors

Solid Cancers Clinical Trial

Official title:

A Phase Ib, Open Label, Dose Escalation Study of the Safety and Pharmacology of GDC-0980 in Combination With a Fluoropyrimidine, Oxaliplatin, and Bevacizumab in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01332604
• Other study ID #: PIM4945g
• Secondary ID: GO00883
• Status: Completed
• Phase: Phase 1
• First received: March 31, 2011
• Last updated: November 1, 2016
• Start date: July 2011
• Est. completion date: June 2015

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 is an open-label, multicenter, Phase Ib, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral GDC-0980 administered in combination with capecitabine and with mFOLFOX6 chemotherapy with bevacizumab added on at Cycle 5 in patients with advanced or metastatic solid tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically documented locally advanced or metastatic solid tumors for which established therapy is ineffective, not tolerable, or does not exist

• Patients with histologically or cytologically documented locally advanced or metastatic breast cancer who have received at least one prior chemotherapy-based regimen for incurable disease (Arm A)

• Patients with histologically or cytologically documented locally advanced or metastatic CRC who have not received prior oxaliplatin-based therapy within 1 year of initiation of study treatment. (Arm B)

Exclusion Criteria:

• Prior anti-cancer therapy that fulfills the following criteria: a total of more than six courses of an alkylating agent, a total of more than four courses of carboplatin-containing chemotherapy regimens, and a total of more than two courses of nitrosoureas or mitomycin C, high-dose chemotherapy requiring stem-cell support, and irradiation to >= 25% of bone marrow-bearing areas

• Current dyspnea at rest because of complications of advanced malignancy or other disease requiring continuous oxygen therapy

• Known deficiency of dihydropyrimidine dehydrogenase (DPD)

• Bisphosphonate therapy for symptomatic hypercalcemia

• Known untreated or active central nervous system (CNS) metastases

• Pregnancy, lactation, or breastfeeding

For Arm B:

• Inadequately controlled hypertension

• Prior history of hypertensive crisis or hypertensive encephalopathy

• History of myocardial infarction or unstable angina within 6 months prior to the first dose of study treatment

• History of stroke or transient ischemic attacks within 6 months prior to the first dose of study treatment

• Significant vascular disease within 6 months prior to the first dose of study treatment

• History of hemoptysis within 1 month prior to the first dose of study treatment

• Patients with one or more pulmonary tumor masses with evidence of cavitation

• Evidence of bleeding diathesis or significant coagulopathy

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to the first dose of study treatment

• History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to the first dose of study treatment

• Clinical signs or symptoms of GI obstruction or requirement for parenteral hydration, parenteral nutrition, or tube feeding

• Evidence of abdominal free air not explained by paracentesis or recent surgical procedure

• Serious, non-healing wound, active ulcer, or untreated bone fracture

• The presence of an ulcerating breast cancer tumor will not render a patient ineligible

• Proteinuria

Study Design

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

Related Conditions & MeSH terms

• Solid Cancers

Intervention

Drug:
• GDC-0980
Oral escalating dose
• bevacizumab
Intravenous repeating dose
• capecitabine
Oral repeating dose
• mFOLFOX6
Intravenous repeating dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events		Up to 30 days after last dose of study treatment	No
Primary	Incidence of dose limiting toxicities (DLTs)		Up to Day 21 for Arm A and up to Day 28 for Arm B	No
Primary	Nature of adverse events graded according to NCI CTCAE, v4.0		Up to 30 days after last dose of study treatment	No
Primary	Nature of dose limiting toxicities (DLTs)graded according to NCI CTCAE, v4.0		Up to 28 days	No
Primary	Severity of adverse events		Up to 30 days after last dose of study treatment	No
Secondary	Total exposure from Time 0 to the last measurable concentration		Up to Day 2 for Arm B and up to Day 9 for Arm A	No
Secondary	Maximum observed plasma concentration		Up to Day 2 for Arm B and up to Day 9 for Arm A	No
Secondary	Minimum observed plasma concentration		Up to Day 2 for Arm B and up to Day 9 for Arm A	No
Secondary	Time to maximum observed plasma concentration		Up to Day 2 for Arm B and up to Day 9 for Arm A	No