A Study of the Safety and Pharmacology Of PI3-Kinase Inhibitor GDC-0941 In Combination With Either Paclitaxel And Carboplatin (With or Without Bevacizumab) or Pemetrexed, Cisplatin, And Bevacizumab in Patients With Advanced Non-Small Cell Lung Cancer

Genentech

Status and phase: Completed; Phase 1

Conditions: Non-Squamous Non-Small Cell Lung Cancer

Treatments: Drug: pemetrexed; Drug: GDC-0941; Drug: cisplatin; Drug: paclitaxel; Drug: bevacizumab; Drug: carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00974584

GO01303 (Other Identifier)

GDC4628g

Details and patient eligibility

About

This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of oral (PO) GDC-0941 administered with one of three planned regimens: Arm A: paclitaxel and carboplatin in bevacizumab-ineligible NSCLC patients, Arm B: paclitaxel, carboplatin, and bevacizumab in bevacizumab-eligible NSCLC patients and Arm C: pemetrexed, cisplatin, and bevacizumab in bevacizumab-eligible, non-squamous NSCLC patients.

Enrollment: 65 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically documented NSCLC with advanced disease (Stage IIIb not eligible for chemoradiotherapy or Stage IV or recurrent disease)
• Adequate organ function as assessed by laboratory tests
• Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST)

Exclusion criteria

• More than one anti-cancer regimen (chemotherapy or radiotherapy) for advanced NSCLC prior to initiation of study treatment
• Any adjuvant or neoadjuvant anti-cancer therapy within a specified timeframe prior to first study treatment
• History of Grade >= 3 fasting hyperglycemia or diabetes requiring regular medication
• Active autoimmune disease, active infection requiring IV antibiotics, or other current uncontrolled illness
• History of clinically significant cardiac or pulmonary dysfunction
• History of malabsorption syndrome or other condition that would interfere with enteral absorption
• Clinically significant history of liver disease
• Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytic agents
• Known brain metastases that are untreated, symptomatic, or require therapy
• Pregnancy, lactation, or breastfeeding

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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65 participants in 4 patient groups

GDC-0941+Paclitaxel+Carboplatin

Experimental group

Description:

Bevacizumab-ineligible non-small cell lung cancer (NSCLC) participants may receive up to 6 cycles (21-day cycle) of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941

Treatment:

Drug: GDC-0941

Drug: paclitaxel

Drug: carboplatin

GDC-0941+Paclitaxel+Carboplatin+Bevacizumab

Experimental group

Description:

Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.

Treatment:

Drug: GDC-0941

Drug: paclitaxel

Drug: bevacizumab

Drug: carboplatin

GDC-0941+Pemetrexed+Cisplatin

Experimental group

Description:

Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\\n

Treatment:

Drug: GDC-0941

Drug: cisplatin

Drug: bevacizumab

Drug: pemetrexed

GDC-0941+Pemetrexed+Cisplatin+Bevacizumab

Experimental group

Description:

Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\\n

Treatment:

Drug: GDC-0941

Drug: cisplatin

Drug: bevacizumab

Drug: pemetrexed