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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01332604
• Collaborator: (none)
• Enrollment: 41
• Locations: 4
• Arms: 2
• Duration (Months): 47
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Cancers	Drug: GDC-0980; Drug: bevacizumab; Drug: capecitabine; Drug: mFOLFOX6	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: GDC-0980; Oral escalating dose; Drug: capecitabine; Oral repeating dose
Experimental: B	Drug: GDC-0980; Oral escalating dose; Drug: bevacizumab; Intravenous repeating dose; Drug: mFOLFOX6; Intravenous repeating dose

Outcome Measures

Primary Outcome Measures

1. Incidence of adverse events [Up to 30 days after last dose of study treatment]

2. Incidence of dose limiting toxicities (DLTs) [Up to Day 21 for Arm A and up to Day 28 for Arm B]

3. Nature of adverse events graded according to NCI CTCAE, v4.0 [Up to 30 days after last dose of study treatment]

4. Nature of dose limiting toxicities (DLTs)graded according to NCI CTCAE, v4.0 [Up to 28 days]

5. Severity of adverse events [Up to 30 days after last dose of study treatment]

Secondary Outcome Measures

1. 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]

2. Maximum observed plasma concentration [Up to Day 2 for Arm B and up to Day 9 for Arm A]

3. Minimum observed plasma concentration [Up to Day 2 for Arm B and up to Day 9 for Arm A]

4. Time to maximum observed plasma concentration [Up to Day 2 for Arm B and up to Day 9 for Arm A]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States	90095
2		Aurora	Colorado	United States	80045
3		Rochester	Minnesota	United States	55905
4		Barcelona		Spain	08035

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT01332604
• Other Study ID Numbers: PIM4945g; GO00883
• First Posted: Apr 11, 2011
• Last Update Posted: Nov 2, 2016
• Last Verified: Nov 1, 2016

• Additional relevant MeSH terms: Bevacizumab; Capecitabine

Study Results

No Results Posted as of Nov 2, 2016