Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Carcinoma

Lung Neoplasms

Recurrence

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Patients receive taselisib PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Taselisib

Vassiliki Papadimitrakopoulou

This phase II trial studies how well taselisib (GDC-0032) works in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a sub-study that includes all screened patients positive for the phosphoinositide 3-kinase (PI3K) biomarker. PI3K can cause tumor cells to grow more quickly. Taselisib may decrease the activity of PI3K and may be able to shrink tumors.

PRIMARY OBJECTIVES:

I. Phase II Component: To evaluate if there is sufficient evidence to continue to the phase III component by evaluating the objective response rate (ORR) for PI3K Genentech (GNE)-positive patients registered to S1400B treated with GDC-0032. (Phase II)

II. Phase III Component: If the study meets the criteria specified in S1400, the study will be amended to include a follow-on randomized phase III trial.

SECONDARY OBJECTIVES:

I. To evaluate investigator-assessed progression free survival (IA-PFS) and overall survival (OS) in both the subset of patients defined to be PI3K GNE-positive and in the entire S1400B (PI3K Foundation Medicine \[FMI\] positive) study population treated with GDC-0032. (Phase II)

II. To evaluate ORR in the entire S1400B (PI3K FMI positive) study population treated with GDC-0032 to evaluate the duration of response (DoR) both in GNE positive and FMI positive. (Phase II)

III. To evaluate the DoR both in the entire S1400B PI3K FMI positive study population and in GNE positive patients treated with GDC-0032 who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. (Phase II)

IV. To evaluate the frequency and severity of toxicities associated with GDC-0032. (Phase II)

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To identify additional predictive tumor/blood biomarkers that may modify response or define resistance to the GDC-0032 beyond the chosen biomarker for biomarker-driven sub-studies.

II. To identify potential resistance biomarkers at disease progression.

III. To establish a tissue/ blood repository from patients with refractory squamous cell carcinoma (SCCA) of the lung.

OUTLINE: As of 12/18/2015, patients are assigned to Arm I.

ARM I: Patients receive taselisib orally (PO) daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel intravenously (IV) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to Arm III.

Re-registration ARM III: Patients in Arm II eligible for re-registration receive taselisib orally (PO) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, all patients are followed up every 6 months for the first 2 years and then at the end of the year 3 from date of sub-study/re-registration.

Lung-MAP: Taselisib as Therapy in Treating Patients With Stage IV Squamous Cell Lung Cancer and Positive Biomarker Matches

A Phase II Study of GDC-0032 (Taselisib) for Previously Treated PI3K Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung-MAP Sub-Study)

ORR-the percentage of PI3K GNE-positive participants with confirmed and unconfirmed, partial response and complete response to treatment with GDC-0032 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).

From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration or death due to any cause.

From date of sub-study registration to date of death due to any cause assessed by local review.

Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).

Among participants who had a response, duration is calculated from registration to response date.

Frequency and severity of toxicities greater than Grade 2 associated with GDC-0032.

National Cancer Institute (NCI)

SWOG Cancer Research Network

GDC-0032

Patients receive taselisib PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Taselisib: Given PO

Arm I (GDC-0032)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

PI3K GNE-Positive

Measure Description:

0: Fully active, able to carry on all pre-disease performance without restriction. 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work. 2: Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours. 3: Capable of limited self-care, confined to bed or chair more than 50% of waking hours.4: Completely disabled; cannot carry on any self-care; totally confined to bed or chair.

Performance Status

Smoking History

All eligible participants that received protocol treament

Lung Committee Statistician

Participants receive taselisib PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Taselisib: Given PO

Objective Response Rate (ORR) for PI3K GNE-positive Participants Registered to S1400B Treated With GDC-0032.

PI3K GNE-positive subset

Full eligible population

PI3K GNE-positive subset (21 participants) and full eligible population (26 participants)

Investigator-assessed Progression Free Survival (IA-PFS) in Both the Subset of Participants Defined to be PI3K GNE-positive and in the Entire S1400B (PI3K FMI Positive) Study Population Treated With GDC-0032.

Investigator-assessed Overall Survival (OS) in Both the Subset of Participants Defined to be PI3K GNE-positive and in the Entire S1400B (PI3K FMI Positive) Study Population Treated With GDC-0032.

Eligible participants that received protocol treatment.

ORR in the Entire S1400B (PI3K FMI Positive) Study Population Treated With GDC-0032.

Duration of Response (DoR) Both in the Entire S1400B PI3K FMI Positive Study Population and in GNE Positive Participants Treated With GDC-0032 Who Achieve a CR or PR (Confirmed and Unconfirmed) by RECIST 1.1.

Cardiac arrest

Dehydration

Diarrhea

Dyspnea

Fatigue

Hyperglycemia

Hypertension

Hyponatremia

Hypoxia

Lung infection

Lymphocyte count decreased

Nausea

Platelet count decreased

Pneumonitis

Pneumothorax

Rash maculo-papular

Respiratory failure

Vomiting

Eligible participants that received protocol treatment and had greater than grade 2 toxicity.

Frequency and Severity of Toxicities Associated With GDC-0032. (Phase II)

Overall Study

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Adenocarcinoma

Adenocarcinoma of Lung

Disease Attributes

Lung Adenocarcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Paclitaxel

Carboplatin

Bevacizumab

Cetuximab

Albumin-Bound Paclitaxel

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Roy Herbst

This randomized phase III trial studies carboplatin and paclitaxel to compare how well they work with or without bevacizumab and/or cetuximab in treating patients with stage IV or non-small cell lung cancer that has returned after a period of improvement (recurrent). Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab may prevent the growth of new blood vessels that tumor needs to grow. Cetuximab may also stop cancer cells from growing by binding and interfering with a protein on the surface of the tumor cell that is needed for tumor growth. It is not yet known whether giving carboplatin and paclitaxel are more effective with or without bevacizumab and/or cetuximab in treating patients with non-small cell lung cancer.

PRIMARY OBJECTIVES:

I. To compare overall survival (OS) in the entire study population. II. To compare progression-free survival (PFS) by institutional review of epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH)-positive patients.

SECONDARY OBJECTIVES:

I. To compare OS and PFS by centralized review in EGFR FISH-positive patients. II. To compare PFS by centralized image review and by institutional review in the entire study population.

III. To compare the response rate (confirmed plus unconfirmed, complete and partial responses) in a subset of patients with measurable disease in EGFR FISH-positive patient and the entire study population.

IV. To assess the toxicities of these treatment regimens. V. To prospectively test EGFR FISH as a predictive marker for the selection of patients for cetuximab plus chemotherapy.

III. To evaluate the role of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in terms of cetuximab efficacy.

IV. To compare the results of EGFR FISH with KRAS mutations, EGFR mutations, EGFR immunohistochemistry (IHC), and other purported EGFR-related biomarkers.

TERTIARY OBJECTIVES:

I. To compare PFS in patients with advanced non-small cell lung cancer (NSCLC) with an IHC score \> 200 treated with carboplatin, paclitaxel, and bevacizumab (if appropriate) with or without cetuximab.

II. To compare OS in patients with advanced NSCLC with an IHC score \> 200 treated with carboplatin, paclitaxel, and bevacizumab (if appropriate) with or without cetuximab.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.

S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer

A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab With or Without Concurrent Cetuximab in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever comes first by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as assessed by the treating investigator.Patients last known to be alive and progression-free are censored at date of last contact. Progression is defined using RECIST 1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

Limited to eligible patients who started treatment, who did not have a major deviation in the treatment protocol, and whose toxicity profile has been completed.

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Arm I (Chemo +/- Bevacizumab)

Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Cetuximab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Arm II (Chemo, Cetuximab, +/- Bevacizumab)

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Total

Age, Categorized

Age, Customized

Race

Race/Ethnicity, Customized

M staging per AJCC Cancer Staging Manual, 7th Edition, 2009. M1a: Separate tumor nodule(s) in a contralateral lobe; tumor with pleural nodules or malignant pleural (or pericardial) effusion.

M1b: Distant metastases

M-stage

Bevacizumab treatment

'Other' includes large-cell carcinoma, bronchioloalveolar carcinoma, mixed, other, and not reported.

Histology

Patients will be graded according to the Zubrod Performance Status Scale. 0 Fully active, able to carry on all pre-disease performance without restriction.

1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.

EGFR (Epidermal Growth Factor Receptor) FISH (Fluorescence In Situ Hybridization) status

Only eligible patients are included in the analysis.

Lung Committee Statistican

All eligible patients are included in the analysis.

Overall Survival (OS) in the Entire Study Population

Eligible patients with EGFR FISH positive are included in the analysis.

Progression-free Survival (PFS) of EGFR FISH-positive Patients by Institutional Review

Eligible and evaluable participants who were EGFR-FISH positive

Overall Survival (OS) of EGFR FISH-positive Patients

Data are not available for this outcome as central image review was not performed. The study was closed for futility at the interim analysis and therefore there was no need to confirm PFS by central review.

Progression-Free Survival (PFS) of EGFR FISH-positive Patients by Centralized Review

Progression-Free Survival (PFS) of the Entire Study Population by Institutional Review

Progression-Free Survival (PFS) of the Entire Study Population by Centralized Review

Eligible EGFR FISH positive patients with baseline measurable disease are included in the analysis.

Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in EGFR FISH-positive Patients

Eligible patients with baseline measurable disease are included in the analysis.

Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in the Entire Study Population

ALT, SGPT (serum glutamic pyruvic transaminase)

AST, SGOT

Acidosis (metabolic or respiratory)

Adrenal insufficiency

Albumin, serum-low (hypoalbuminemia)

Alkaline phosphatase

Allergic reaction/hypersensitivity

Allergy/Immunology-Other (Specify)

Anorexia

Apnea

Aspiration

Ataxia (incoordination)

Bilirubin (hyperbilirubinemia)

Blood/Bone Marrow-Other (Specify)

Bronchospasm, wheezing

CNS cerebrovascular ischemia

Calcium, serum-high (hypercalcemia)

Calcium, serum-low (hypocalcemia)

Carbon monoxide diffusion capacity (DL(co))

Cardiac General-Other (Specify)

Cardiac troponin I (cTnI)

Cardiac-ischemia/infarction

Cardiopulmonary arrest, cause unknown (non-fatal)

Cognitive disturbance

Colitis

Colitis, infectious (e.g., Clostridium difficile)

Conduction abnormality - Asystole

Confusion

Constipation

Cough

Creatinine

Cytokine release syndrome/acute infusion reaction

Death - Multi-organ failure

Death not associated with CTCAE term - Death NOS

Dermatology/Skin-Other (Specify)

Dizziness

Dry eye syndrome

Dry mouth/salivary gland (xerostomia)

Dry skin

Dysphagia (difficulty swallowing)

Dyspnea (shortness of breath)

Edema: limb

Encephalopathy

Esophagitis

Extrapyramidal/involuntary movement/restlessness

Eyelid dysfunction

Fatigue (asthenia, lethargy, malaise)

Febrile neutropenia

Fever in absence of neutropenia, ANC lt1.0x10e9/L

GGT (gamma-glutamyl transpeptidase)

Gastritis (including bile reflux gastritis)

Gastrointestinal-Other (Specify)

Glucose, serum-high (hyperglycemia)

Glucose, serum-low (hypoglycemia)

Heartburn/dyspepsia

Hemoglobin

Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lung-MAP: Taselisib as Therapy in Treating Patients With Stage IV Squamous Cell Lung Cancer and Positive Biomarker Matches	NCT02785913	Recurrent Squam... Stage IV Squamo...	Laboratory Biom... Taselisib	18 Years -	SWOG Cancer Research Network
Lung-MAP: Taselisib as Therapy in Treating Patients With Stage IV Squamous Cell Lung Cancer and Positive Biomarker Matches	NCT02785913	Recurrent Squam... Stage IV Squamo...	Laboratory Biom... Taselisib	18 Years -	SWOG Cancer Research Network
S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer	NCT00946712	Recurrent Large... Recurrent Lung ... Recurrent Squam... Stage IV Large ... Stage IV Lung A... Stage IV Squamo...	Bevacizumab Carboplatin Cetuximab Laboratory Biom... Paclitaxel	18 Years -	SWOG Cancer Research Network

Spots Global Cancer Trial Database for stage iv squamous cell lung carcinoma