A Study of the Safety and Pharmacology of GDC-0980 in Combination With Either Paclitaxel and Carboplatin (With or Without Bevacizumab) or Pemetrexed and Cisplatin in Patients With Solid Tumors

Study Overview
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Brief Summary
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This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0980 administered with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin to patients with locally advanced or metastatic solid tumors.

Official Title
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A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0980 in Combination With Either Paclitaxel and Carboplatin (With or Without Bevacizumab) or Pemetrexed and Cisplatin in Patients With Solid Tumors

Conditions
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Solid Cancers

Intervention / Treatment
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* Drug: GDC-0980
* Drug: bevacizumab
* Drug: carboplatin
* Drug: cisplatin
* Drug: paclitaxel
* Drug: pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented, incurable, locally advanced, or metastatic solid malignancy Adequate hematologic and end organ function For female patients of childbearing potential and male patients with partners of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of the study Measurable disease per RECIST (Response Evaluable Criteria in Solid Tumors), with the exception of prostate cancer (two rising PSA Levels that meet the criteria of progression per PSA Working Group) and ovarian cancer (two rising CA-125 levels greater than the ULN) Exclusion Criteria: Current dyspnea at rest due to complications of advanced malignancy, or other conditions requiring continuous supplemental oxygen Uncontrolled hypomagnesemia or hypokalemia History of Grade >= 3 fasting hyperglycemia Any condition requiring full-dose anticoagulants Known HIV infection Known untreated or active central nervous system (CNS) metastases Pregnancy, lactation, or breastfeeding Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of study treatment or anticipation of need for major surgical procedure during the course of the study For Arm B: Conditions that preclude the use of bevacizumab For Arm C: Conditions that preclude the use of pemetrexed or cisplatin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: GDC-0980<br>* Oral escalating dose<br>Drug: carboplatin<br>* Intravenous repeating dose<br>Drug: paclitaxel<br>* Intravenous repeating dose<br>|
| Experimental: B<br> | Drug: GDC-0980<br>* Oral escalating dose<br>Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: carboplatin<br>* Intravenous repeating dose<br>Drug: paclitaxel<br>* Intravenous repeating dose<br>|
| Experimental: C<br> | Drug: GDC-0980<br>* Oral escalating dose<br>Drug: cisplatin<br>* intravenous repeating dose<br>Drug: pemetrexed<br>* intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Up to 30 days after last dose of study treatment or initiation of new anti-cancer therapy, whichever comes first | 
| Incidence of dose limiting toxicities (DLTs) |  | Up to 21 days from Last Patient In (LPI) in Stage 1 of study | 
| Nature of adverse events |  | Up to 30 days after last dose of study treatment or initiation of new anti-cancer therapy, whichever comes first | 
| Nature of dose limiting toxicities (DLTs) |  | Up to 21 days from Last Patient In (LPI) in Stage 1 of study | 
| Severity of adverse events |  | Up to 30 days after last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total exposure |  | Up to 32 months or early study discontinuation | 
| Maximum plasma concentration |  | Up to 32 months or early study discontinuation | 
| Time to maximum observed plasma concentration |  | Up to 32 months or early study discontinuation | 
| Plasma half-life |  | Up to 32 months or early study discontinuation |