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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01332604
First received: March 31, 2011
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Solid Cancers
Drug: bevacizumab
Drug: capecitabine
Drug: GDC-0980
Drug: mFOLFOX6
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: Up to 30 days after last dose of study treatment ] [ Designated as safety issue: No ]
  • Incidence of dose limiting toxicities (DLTs) [ Time Frame: Up to Day 21 for Arm A and up to Day 28 for Arm B ] [ Designated as safety issue: No ]
  • Nature of adverse events graded according to NCI CTCAE, v4.0 [ Time Frame: Up to 30 days after last dose of study treatment ] [ Designated as safety issue: No ]
  • Nature of dose limiting toxicities (DLTs)graded according to NCI CTCAE, v4.0 [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
  • Severity of adverse events [ Time Frame: Up to 30 days after last dose of study treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Total exposure from Time 0 to the last measurable concentration [ Time Frame: Up to Day 2 for Arm B and up to Day 9 for Arm A ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration [ Time Frame: Up to Day 2 for Arm B and up to Day 9 for Arm A ] [ Designated as safety issue: No ]
  • Minimum observed plasma concentration [ Time Frame: Up to Day 2 for Arm B and up to Day 9 for Arm A ] [ Designated as safety issue: No ]
  • Time to maximum observed plasma concentration [ Time Frame: Up to Day 2 for Arm B and up to Day 9 for Arm A ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: July 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B Drug: bevacizumab
Intravenous repeating dose
Drug: GDC-0980
Oral escalating dose
Drug: mFOLFOX6
Intravenous repeating dose
Experimental: A Drug: capecitabine
Oral repeating dose
Drug: GDC-0980
Oral escalating dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01332604

Locations
United States, California
Los Angeles, California, United States, 90095
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Minnesota
Rochester, Minnesota, United States, 55905
Spain
Barcelona, Spain, 08035
Sponsors and Collaborators
Genentech
Investigators
Study Director: Clinical Trials Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01332604     History of Changes
Other Study ID Numbers: PIM4945g, GO00883
Study First Received: March 31, 2011
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Oxaliplatin
Capecitabine
Bevacizumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014