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

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2011-002893-21-GB
• Date of registration: 29/02/2012
• Prospective Registration: No
• Primary sponsor: Genentech, Inc.
• Public title: 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
• Scientific title: A PHASE II, DOUBLE-BLIND, PLACEBO CONTROLLED, RANDOMIZED STUDY EVALUATING THE SAFETY AND EFFICACY OF CARBOPLATIN/PACLITAXEL AND CARBOPLATIN/PACLITAXEL/BEVACIZUMAB WITH AND WITHOUT GDC-0941 IN PATIENTS WITH PREVIOUSLY UNTREATED ADVANCED OR RECURRENT NON-SMALL CELL LUNG CANCER
• Date of first enrolment: 23/02/2012
• Target sample size: 496
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002893-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 6

Countries of recruitment

Argentina, Australia, Brazil, Canada, Chile, France, Germany, Hungary, Israel, Italy, Netherlands, Russian Federation, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Genentech Trial Information Support
• Affiliation: Genentech

• Name: Genentech Trial Information Support
• Affiliation: Genentech

Key inclusion & exclusion criteria

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
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 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 immunosuppressants (e.g., sulfasalaz

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

PREVIOUSLY UNTREATED ADVANCED OR RECURRENT NON-SMALL CELL LUNG CANCER
MedDRA version: 16.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: GDC-0941/RO5314482
Product Code: GDC-0941
Pharmaceutical Form: Film-coated tablet
CAS Number: 957054-33-0
Current Sponsor code: GDC-0941/RO5314482
Other descriptive name: GDC-0941.180
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: GDC-0941/RO5314482
Product Code: GDC-0941
Pharmaceutical Form: Film-coated tablet
CAS Number: 957054-33-0
Current Sponsor code: GDC-0941/RO5314482
Other descriptive name: GDC-0941.180
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Avastin
Product Name: Avastin (Bevacizumab)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Paclitaxel-GRY
Product Name: Paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Trade Name: Carboplatin-GRY
Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CARBOPLATIN
CAS Number: 41575-94-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Paclitaxel
Product Name: Paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Trade Name: Paclitaxel
Product Name: Paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXE

Primary Outcome(s)

Primary end point(s): For ALL Arms and all predefined study populations (see Section 3.5), the
primary efficacy outcome measure is:
• PFS, defined as the time from randomization to NSCLC disease progression as assessed by the investigator per RECIST v1.1 (Appendix C) or death from any cause on study (= 30 days after the last dose of study treatment) whichever occurs first

Timepoint(s) of evaluation of this end point: Please see E.5.1

Secondary Objective: Due to the character limit for this field, please refer to protocol section 2.2 for secondary objectives

Main Objective: Part I
•To evaluate the efficacy (as measured by PFS) of GDC-0941 340mg+carboplatin+paclitaxel (Arm A) versus carboplatin+paclitaxel (Arm B) in all patients with squamous NSCLC
•To evaluate the efficacy (as measured by PFS) of GDC-0941 340mg+carboplatin+paclitaxel (Arm A) versus carboplatin+paclitaxel (Arm B) in patients with squamous NSCLC with PIK3CA amplification
•To evaluate the efficacy (as measured by PFS) of GDC-0941 340mg+carboplatin+paclitaxel+bevacizumab (Arm C) versus carboplatin+paclitaxel+bevacizumab (Arm D) in all patients with non-squamous NSCLC
•To evaluate the efficacy (as measured by PFS) of GDC-0941 340mg+carboplatin+paclitaxel+bevacizumab (Arm C) versus carboplatin+paclitaxel+bevacizumab (Arm D) in patients with non-squamous NSCLC with PTEN-loss/low status
Part II
•To evaluate the efficacy (as measured by PFS) of GDC-0941 260mg+ carboplatin+paclitaxel+bevacizumab (Arm E) versus carboplatin+paclitaxel+bevacizumab (Arm F) in all patients with non-squamous NSCLC

Secondary Outcome(s)

Secondary end point(s): For ALL Arms and all predefined study populations (see Section 3.5), the secondary efficacy outcome measures are:
• Objective tumor response as assessed by the investigator using RECIST v1.1 (Appendix C); objective responses must be confirmed = 28 days after initial response
• Duration of objective response, defined as the time from first observation of an objective tumor response until first observation of disease progression as assessed by the investigator using RECIST v1.1 (Appendix C)
• OS, defined as the time from randomization until death from any cause

Timepoint(s) of evaluation of this end point: Please see E.5.2

Secondary ID(s)

GO27912

2011-002893-21-DE

Source(s) of Monetary Support

Genentech