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

NCT01332604 | Completed Phase 1

• 2 other identifiers: PIM4945gGO00883
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 4

Brief 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.

Conditions

Solid Cancers

Outcome Measures

Primary Outcomes (5)

• Incidence of adverse events

  Up to 30 days after last dose of study treatment

• Incidence of dose limiting toxicities (DLTs)

  Up to Day 21 for Arm A and up to Day 28 for Arm B

• Nature of adverse events graded according to NCI CTCAE, v4.0

  Up to 30 days after last dose of study treatment

• Nature of dose limiting toxicities (DLTs)graded according to NCI CTCAE, v4.0

  Up to 28 days

• Severity of adverse events

  Up to 30 days after last dose of study treatment

Secondary Outcomes (4)

• 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

• Maximum observed plasma concentration

  Up to Day 2 for Arm B and up to Day 9 for Arm A

• Minimum observed plasma concentration

  Up to Day 2 for Arm B and up to Day 9 for Arm A

• Time to maximum observed plasma concentration

  Up to Day 2 for Arm B and up to Day 9 for Arm A

Study Arms (2)

A

EXPERIMENTAL

Drug: GDC-0980; Drug: capecitabine

B

EXPERIMENTAL

Drug: GDC-0980; Drug: bevacizumab; Drug: mFOLFOX6

Interventions

GDC-0980 DRUG

Oral escalating dose

A; B

bevacizumab DRUG

Intravenous repeating dose

B

capecitabine DRUG

Oral repeating dose

A

mFOLFOX6 DRUG

Intravenous repeating dose

B

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (4)

Unknown Facility

Los Angeles, California, 90095, United States

Location

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

Rochester, Minnesota, 55905, United States

Location

Unknown Facility

Barcelona, Barcelona, 08035, Spain

Location

MeSH Terms

Interventions

1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno(3,2-d)pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one; Bevacizumab; Capecitabine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2011
• First Posted: April 11, 2011
• Study Start: July 1, 2011
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

US (3); ES (1)