Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Adenocarcinoma

Adenocarcinoma of Lung

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Micronutrients

Hematinics

Vitamins

Bevacizumab

Pemetrexed

Cisplatin

Certolizumab Pegol

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Tumor Necrosis Factor Inhibitors

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

Patients will receive certolizumab with 6 cycles of cisplatin \& pemetrexed. Cycle of chemo will be 3 weeks. Certolizumab will be adm in the following fashion: first dose administered at the time of treatment initiation, second dose will be given after 2 weeks of treatment, third dose after four weeks of treatment, \& subsequent doses given every 4 weeks thereafter. Patients will be monitored for progression of disease using RECIST 1.1 with scans to be performed every 6 weeks. Posttreatment biopsies will be performed at the time of treatment discontinuation. Two dose levels of certolizumab will be tested, 200mg \& 400mg. A non-therapeutic cohort of 10 patients with adenocarcinomas who will be undergoing standard of care treatment with platinum based chemotherapy + pemetrexed +/- bevacizumab will be consented for blood draws before each cycle of treatment. This blood will be analyzed for cytokines and will serve as a reference for the experimental arm.

Certolizumab

cisplatin

pemetrexed

Paul Paik

The purpose of this study is to test the safety of certolizumab when it is given with the chemotherapy drugs cisplatin and pemetrexed. Cisplatin and pemetrexed are two chemotherapy drugs used in the treatment of lung cancer. The investigators want to find out what effects, good and/or bad, certolizumab has on the patient and lung cancer.

Certolizumab in Combination With Chemotherapy for Patients With Stage IV Lung Adenocarcinomas

A Phase I Trial of Certolizumab in Combination With Chemotherapy for Patients With Stage IV Lung Adenocarcinomas

A standard 3+3 dose-escalation scheme will be used to test two doses of certolizumab: dose level A (200mg) and dose level B (400mg), in combination with the standard dose of chemotherapy. In addition, two de-escalation doses are planned, if dose level A proves too toxic: dose level C (chemotherapy at 75% of the standard dose + certolizumab 200mg) and dose level D (chemotherapy at 75% of the standard dose + certolizumab 400mg)..The MTD is the highest dose at which ≤ 1/6 patients experiences a DLT. Please see the dose escalation schema for exact dose level details.

Patients will be followed from the first drug administration until disease progression (by RECIST 1.1) or death, whichever comes first. Patients alive who have not progressed by the end of the study time will be censored at the time of the last available follow-up. PFS probability will be estimated using Kaplan-Meier methods.

Biopsies will be performed pre- and post-treatment in all patients and will undergo immunohistochemical staining of TNF-alpha, CXCL1/2, and S100A8/9. Staining will be scored from 0-4. The difference in IHC score from post-treatment to baseline will be compared between patients who have, at minimum, evidence of stable disease during treatment (CR+PR+SD) and the remaining patients, using non-parametric Wilcoxon signed rank test.

National Cancer Institute (NCI)

Memorial Sloan Kettering Cancer Center

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Recurrence

Disease Attributes

Lung Diseases

Respiratory Tract Diseases

Antibodies

Antibodies, Monoclonal

Paclitaxel

Carboplatin

Cetuximab

Albumin-Bound Paclitaxel

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

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.

Laboratory Biomarker Analysis

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.

SWOG Cancer Research Network

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, Continuous

Age, Categorized

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

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

Smoking History

'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.

Performance Status

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

Dehydration

Dermatology/Skin-Other (Specify)

Diarrhea

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

Hemolysis

Hemorrhage, GI - Abdomen NOS

Hemorrhage, GI - Duodenum

Hemorrhage, GI - Esophagus

Hemorrhage, GI - Jejunum

Hemorrhage, GI - Lower GI NOS

Hemorrhage, GI - Upper GI NOS

Hemorrhage, GI - Varices (esophageal)

Hemorrhage, GI - Varices (rectal)

Hemorrhage, pulmo/upper resp- Bronchopulmonary NOS

Hemorrhage, pulmonary/upper respiratory - Lung

Hemorrhage, pulmonary/upper respiratory - Nose

Hemorrhage, pulmonary/upper respiratory - Pleura

Hemorrhage/Bleeding-Other (Specify)

Hiccoughs (hiccups, singultus)

Hot flashes/flushes

Hypertension

Hypotension

Hypoxia

INR (of prothrombin time)

Inf (clin/microbio) w/Gr 3-4 neuts - Blood

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Certolizumab in Combination With Chemotherapy for Patients With Stage IV Lung Adenocarcinomas	NCT02120807	Stage IV Lung A...	Certolizumab cisplatin pemetrexed	18 Years -	Memorial Sloan Kettering Cancer Center
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 lung adenocarcinoma