Study of the novel cancer drug GDC-0941 (or placebo) in combination with : a) the approved anticancer drugs carboplatin and paclitaxel; and b) the approved anticancer drugs carboplatin, paclitaxel and bevacizumab in previously untreated patients with advanced non-small cell lung cancer

Phase 1

• Conditions: PREVIOUSLY UNTREATED ADVANCED OR RECURRENT NON-SMALL CELL LUNG CANCER; MedDRA version: 17.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-002893-21-DE
• Lead Sponsor: Genentech, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-02-21
• Last Update Posted: 28 November 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 496

Inclusion Criteria

For ALL Arms, patients must meet the following criteria to undergo screening procedures:
• Signed Informed Consent Form
• All patients must consent to the collection of an archival formalin-fixed paraffin embedded (FFPE) block or freshly cut unstained tumor slides from archival tumor tissue (10–15 preferred, minimum of 5 slides required) or a newly collected tumor sample for PIK3CA amplification testing and/or PTEN IHC, as well as for other protocol-mandated exploratory assessments.
Availability of archival tissue for biomarker testing must be confirmed by the site prior to any study-specific screening procedures.
Suitability of archival non-FFPE tissue must be evaluated by the central or local study pathologist and discussed with the Genentech Medical Monitor.
Patients with no available archival tissue (or if the sample is difficult to obtain) may undergo a new tumor biopsy to meet eligibility criteria, as long as the patient consents to this and the biopsy can be obtained with minimal risk and discomfort to the patient as determined by the local investigator.
Adequate tumor tissue content of the patient’s archival tumor sample must be confirmed by the site’s pathologist or a third-party vendor prior to randomization of the patient (please see Section 4.5.1.e for details).
For Arms A and B, patients must meet the following criteria to be eligible:
• Histologically documented advanced (Stage IV) or recurrent squamous NSCLC
Diagnoses of squamous NSCLC that are based on cytology alone are not acceptable.
Mixed tumors should be categorized according to the predominant cell type.
For Arms C, D, E & F,, patients must meet the following criteria to be eligible:
• Histologically documented advanced (Stage IV) or recurrent non-squamous NSCLC
Diagnoses of non-squamous NSCLC that are based on cytology alone are not acceptable.
Mixed tumors should be categorized according to the predominant cell type.
For ALL Arms, patients must meet the following criteria to be eligible:
• Age = 18 years
• ECO performance status of 0 or 1 (see Appendix E)
• Disease that is measurable per RECIST v1.1 (see Appendix C)
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
Absolute neutrophil count (ANC) = 1500 cells/µL
Without granulocyte colony stimulating factor support within 2 weeks prior to randomization
Platelet count = 100,000/µL
Without transfusion within 2 weeks prior to randomization
Hemoglobin = 9.0 g/dL (90 g/L)
Patients may be transfused to meet this criterion.
Albumin = 3.0 g/dL (30 µmol/L)
Total bilirubin = 1.5 x ULN
AST and ALT = 3.0 x ULN
Serum creatinine = 1.5 x ULN, or creatinine clearance = 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation:
(140-age) x (weight in kg) x (0.85 if female) / 72 x (serum creatinine in mg/dL)
INR = 1.5 and aPTT = 1.5 x ULN, except for patients receiving allowed anti-coagulation therapy
For patients without known type II diabetes, the following is required
Fasting blood glucose < 135 mg/dL (7.49 mmol/L) and HbA1c < 7.0%
For patients with type II diabetes receiving oral anti-hyperglycemic therapy the following is required:
Fasting blood glucose < 160 mg/dL (8.88 mmol/L) and HbA1c < 8.5
Stable regimen of oral anti-hyperglycemic therapy without the use of insulin for at least 3 weeks prior to randomization
Fasting blood glucose levels < 160 mg/dL (8.88 mmol/L) and no hypoglycemia during

Exclusion Criteria

Exlusion criteria for all arms:
•NSCLC with documented EGFR mutation associated with response to
EGFR inhibitors or documented fusion gene involving the anaplastic
lymphoma kinase (ALK) gene (such as EML4-ALK)
•Prior therapy (including chemotherapy, antibody therapy, tyrosine
kinase inhibitors, radiotherapy, immunotherapy, hormonal therapy, or
investigational therapy) before Day1 of Cycle1 for the treatment of
advanced (Stage IV) or recurrent NSCLC
Patients who received prior adjuvant chemotherapy or radiotherapy for
NSCLC are not excluded if the time interval from completion of adjuvant
therapy until disease progression is >12 months
Patients who received prior palliative radiotherapy for metastatic or
lobar lesions (not including target lesions) are not excluded (if >2 weeks
prior to Day1 of Cycle1)
Patients who receive hormone-replacement therapy or oral
contraceptives are not excluded
Patients who received herbal therapy >2 weeks prior to Day1 of Cycle1
are not excluded.
•Evidence of tumor invading major blood vessels on imaging
The investigator or the local radiologist must exclude evidence of tumor
that is fully contiguous with, surrounding, or extending into the lumen of
a major blood vessel (eg pulmonary artery or superior vena cava)
•Known CNS disease except for treated brain metastases
Treated brain metastases are defined as having no evidence of
progression or hemorrhage >2 weeks after treatment & no ongoing
requirement for dexamethasone, as ascertained by clinical examination
and brain imaging (MRI or CT) during the screening period
Stable doses of non-enzyme inducing anti-convulsants are allowed
Treatment for brain metastases may include whole brain radiotherapy,
radiosurgery (Gamma Knife, LINAC, or equivalent) or a combination as
deemed appropriate by the treating physician and if >2 weeks have
passed since radiation treatment
Patients with CNS metastases treated by neurosurgical resection or
brain biopsy performed within 3 months prior to Day1 of Cycle1 will be
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excluded
•Leptomeningeal disease
•Malignancies other than NSCLC successfully treated within 3 years prior
to randomization, except for adequately treated carcinoma in situ of the
cervix, basal or squamous cell skin cancer, localized prostate cancer
treated surgically with curative intent, & carcinoma in situ of any
anatomic location treated with curative intent
•Type I diabetes
•Type II diabetes requiring chronic therapy with insulin
•Requirement for supplemental oxygen therapy to perform activities of
daily living
•Unstable angina
•Serious cardiac arrhythmia requiring medication during the study
•New York Heart Association Class II or greater congestive heart failure
•History of malabsorption syndrome or other condition that would
interfere with enteral absorption
•Major surgical procedure, open biopsy, or significant traumatic injury
within 28 days prior to Day 1 of Cycle 1, or anticipation of need for major
surgical procedure during the course of the study
Placement of vascular access device will not be considered major
surgery
•Clinically significant history of liver disease, including cirrhosis, active
viral hepatitis and current alcohol abuse
•Known HIV infection
•Active infection requiring IV antibiotics
•Active inflammatory diseases that require immunosuppressants,
including small or large intestine inflammation such as Crohn's disease
or ulcerative colitis
- Patients currently receiving immunosu

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified