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

Non-Squamous Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase Ib, Open-Label, Dose-Escalation 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00974584
• Other study ID #: GDC4628g
• Secondary ID: GO01303
• Status: Completed
• Phase: Phase 1
• First received: September 8, 2009
• Last updated: November 1, 2016
• Start date: October 2009
• Est. completion date: March 2015

Study information

• Verified date: November 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Squamous Non-Small Cell Lung Cancer

Intervention

Drug:
• GDC-0941
The GDC-0941 at a starting dose of 60 milligrams (mg) will be administered once daily orally for 14 consecutive days (Days 1 to 14) in 3-week cycles except for the first cycle that has Day 1 of single-agent GDC-0941 preceding Day 2 with combination chemotherapy.\n\n\n\n\n\n
• bevacizumab
Bevacizumab 15 milligrams per kilograms (mg/kg) intravenously (IV) on Day 1 of every 3-week cycle.
• carboplatin
Carboplation IV on Day 1 of every 3-week cycle, at a dose to achieve an area under concentration time curve of 6 milligrams per milliliter*minute (mg/mL*min).\n
• cisplatin
Cisplatin 75 milligrams per square meter (mg/m^2) IV on Day 1 of every 3-week cycle.\n
• paclitaxel
Paclitaxel 200 mg/m^2 IV on Day 1 of every 3-week cycle.\n\n
• pemetrexed
Pemetrexed 500 mg/m^2 IV on Day 1 of every 3-week cycle.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose Limiting Toxicities (DLTs)		Days 1 to 22 of Cycle 1	No
Primary	Percentage of Participants with Adverse Events (AEs)		Up to approximately 5.5 years	No
Secondary	Maximum Plasma Concentration of Paclitaxel		Cycle 1 Day 2: Pre-paclitaxel infusion, end of paclitaxel infusion, 0.5, 1 and 2 hours post-paclitaxel infusion; Cycle 1 Day 3: Pre-GDC-0941 dose, 24 hours post-paclitaxel Day 2 infusion	No
Secondary	Maximum Plasma Concentration of Carboplatin		Cycle 1 Day 2: Pre-carboplatin infusion, end of Carboplatin infusion, 0.5, 1.5 hours post-carboplatin infusion\n\n	No
Secondary	Maximum Plasma Concentration of Pemetrexed		Cycle 1 Day 2: Pre-pemetrexed infusion, end of pemetrexed infusion, 1, 3 hours post-pemetrexed infusion; Cycle 1 Day 3: Pre-GDC-0941 dose, 24 hours post-pemetrexed Day 2 infusion\n\nd be "Yes".	No
Secondary	Maximum Plasma Concentration of Cisplatin		Cycle 1 Day 2: Pre-cisplatin infusion, end of cisplatin infusion, 3 hours post-cisplatin infusion; Cycle 1 Day 3: Pre-GDC-0941 dose, 24 hours post-pemetrexed Day 2 infusion\n\n	No
Secondary	Percentage of Participants with Objective Response (Complete or Partial Response), as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)		Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)\n\n	No
Secondary	Duration of Response, as Assessed Using RECIST\n\n\n		Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)	No
Secondary	Progression-free Survival (PFS), as Assessed Using RECIST\n		Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)\n\n	No
Secondary	Maximum Plasma Concentration of GDC-0941		Cycle 1 Days 1 and 2: Pre-GDC-0941 dose, 1, 2, 3 and 4 hours post-GDC-0941 dose; Cycle 1 Days 3 and 9: Pre-GDC-0941 dose; 30 days after last dose of study treatment (up to approximately 5.5 years)	No