BATTLE-FL: Front-Line Biomarker-Integrated Treatment Study in Non Small Cell Lung Cancer

NCT01263782 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2010-0097NCI-2011-00301
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if knowing biomarker status can help researchers find better treatment combinations for patients with advanced NSCLC. Researchers want to use biomarker status to decide what drug (bevacizumab, or cixutumumab) to give in combination with carboplatin and pemetrexed. The safety of these drug combinations will also be studied.

Conditions

Lung Cancer

Keywords

Non-Small Cell Lung Cancer; NSCLL; Nonsquamous cell; Metastatic disease; Cixutumumab; IMC-A12; Carboplatin; Paraplatin; Pemetrexed; LY231514; Alimta; MTA; Multitargeted Antifolate; NSC-698037; Bevacizumab; Avastin; Anti-VEGF monoclonal antibody; rhuMAb-VEGF

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  It is defined as from treatment start to the time of progression or death, whichever occurred first, or to the time of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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.

  From treatment start to the time of progression or death, whichever occurred first, or to the time of last contact, assessed up to 5 years

Secondary Outcomes (1)

• Overall Response Rate

  From treatment start to every two cycles of completed therapy.

Study Arms (4)

Carboplatin + Pemetrexed

EXPERIMENTAL

The chemotherapy will be Carboplatin (AUC 6) and Pemetrexed (500 mg/m2) every 3 weeks for 4 cycles. Then maintenance Pemetrexed (500 mg/m2 every 3 weeks) will be administered until disease progression or excessive toxicity. If patients are randomized into one of the arms with a biologic therapy, patients will take the chemotherapy prescribed above, but will also receive the biologic therapy during the same time period.

Drug: Carboplatin; Drug: Pemetrexed

Chemo (Carbo/Peme) + Bevacizumab

EXPERIMENTAL

Carboplatin AUC 6 by vein on day 1 of every 21 day cycle for 4 cycles. Pemetrexed 500 mg/m2 by vein on day 1 of each 21 day cycle. Bevacizumab 15 mg/kg by vein on day 1 of each 21 day cycle.

Drug: Carboplatin; Drug: Pemetrexed; Drug: Bevacizumab

Chemo (Carbo/Peme)

EXPERIMENTAL

Carboplatin AUC 6 by vein on day 1 of every 21 day cycle for 4 cycles. Pemetrexed 500 mg/m2 by vein on day 1 of each 21 day cycle.

Drug: Carboplatin; Drug: Pemetrexed

Chemo (Carbo/Peme) + Cixutumumab

EXPERIMENTAL

Carboplatin AUC 6 by vein on day 1 of every 21 day cycle for 4 cycles. Pemetrexed 500 mg/m2 by vein on day 1 of each 21 day cycle. Cixutumumab 20 mg/kg by vein on day 1 of each 21 day cycle.

Drug: Carboplatin; Drug: Pemetrexed; Drug: Cixutumumab

Interventions

Carboplatin DRUG

AUC 6 by vein on day 1 of every 21 day cycle for 4 cycles.

Also known as: Paraplatin

Carboplatin + Pemetrexed; Chemo (Carbo/Peme); Chemo (Carbo/Peme) + Bevacizumab; Chemo (Carbo/Peme) + Cixutumumab

Pemetrexed DRUG

500 mg/m2 by vein on day 1 of each 21 day cycle.

Also known as: LY231514, Alimta, MTA, Multitargeted Antifolate, NSC-698037

Carboplatin + Pemetrexed; Chemo (Carbo/Peme); Chemo (Carbo/Peme) + Bevacizumab; Chemo (Carbo/Peme) + Cixutumumab

Bevacizumab DRUG

15 mg/kg by vein on day 1 of each 21 day cycle.

Also known as: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Chemo (Carbo/Peme) + Bevacizumab

Cixutumumab DRUG

20 mg/kg by vein on day 1 of each 21 day cycle.

Also known as: IMC-A12

Chemo (Carbo/Peme) + Cixutumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has a diagnosis of pathologically confirmed nonsquamous (nonpredominant squamous) NSCLC by tumor biopsy and/or fine-needle aspiration. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the patient is ineligible.
• The patient has a diagnosis of either stage IIIB or stage IV NSCLC or has recurrent NSCLC and is not a candidate for curative treatment. Patients may not have had chemotherapy for the advanced setting.
• The patient has measurable NSCLC.
• The patient's Eastern Cooperative Oncology Group (ECOG) performance status is \</=2 at study entry.
• The patient should have tumor available for epidermal growth factor receptor (EGFR) mutations, ALK fusions and other molecular analyses. If there is no tissue then the patient has should have biopsy accessible tumor.
• The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) \>/= 1,500/mm\^3, platelet count \>/= 100,000/mm\^3, white blood cell count (WBC) \>/= 3,000/ mm\^3, and hemoglobin \>/= 9 g/dL.
• The patient has adequate hepatic function as defined by a total bilirubin level \</= 1.5 X the upper limit of normal (Serum bilirubin \>/= 1.5x Upper Limit of Normal in the setting of known Gilbert's disease is allowed), and alkaline phosphatase, AST and ALT \</= 2.5 X the upper limit of normal or \</= 5.0 x ULN if liver metastases are present.
• The patient has adequate renal function as defined as CrCl of at least 45ml/min.
• If patient has brain metastasis, they must have been stable (treated and/or asymptomatic) and off steroids for at least 2 weeks.
• The patient is \>/= 18 years of age.
• The patient has signed informed consent.
• Pregnancy Test. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for six (6) months after discontinuation of the study drugs. Childbearing potential will be defined as women who have had menses within the past 12 months, who have not had tubal ligation, hysterectomy or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately. The patient, if a man, agrees to use effective contraception or abstinence for the duration of study participation and for six (6) months after discontinuation of the study drugs.
• The ability to interrupt the use of NSAIDS two days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Pemetrexed.

You may not qualify if:

• The patient has received prior definitive therapy (chemotherapy, surgery, or radiotherapy) within 3 months of initiating study drug or within, 2 weeks of localized palliative radiotherapy. Patients treated with initial biologic therapy that progress are eligible (no drug within 4 weeks). Patients must have recovered from the acute toxic effects prior to Day 1 of Cycle 1 to grade \</= 1 or baseline.
• Patients may not have had prior chemotherapy for first line treatment for NSCLC Stage IIIB/IV. Patient with activating EGFR mutations could have been treated with an EGFR tyrosine kinase inhibitor. Similarly patient with ALK or ROS1 fusions could have had treatment with crizotinib or other ALK inhibitors. Patients may not have had prior biologic therapy with antibodies targeting VEGF,or insulin-like growth factor receptor (IGFR).
• The patient has undergone prior thoracic or abdominal surgery within 30 days of study entry, excluding prior diagnostic biopsy.
• The patient has a history of uncontrolled angina, arrhythmias, or congestive heart failure.
• The patient has inadequately controlled hypertension (defined as systolic blood pressure \> 140 and/or diastolic \> 90 mm Hg on antihypertensive medications).
• The patient has a history of stroke or transient ischemic attack within 6 months prior to Day 1 of Cycle 1.
• The patient is unable or unwilling to take folic acid, vitamin B12 supplementation, or dexamethasone according to protocol.
• The patient has neuropathy \>/= grade 2.
• The patient has a history of gastrointestinal fistula, perforation, or abscess, inflammatory bowel disease, or diverticulitis.
• The patient is currently receiving ongoing treatment with full-dose warfarin or equivalent (that is, unfractionated and/or low molecular weight heparin).
• The patient is pregnant.
• The patient is breastfeeding.
• Presence of significant third space fluid which cannot be controlled by drainage.
• The patient's tumor harbors the EML4-ALK fusion gene.
• Drug Specific Eligibility for Treatment Arms. Patients are excluded from the Bevacizumab arm if they have a history of hemoptysis (\>/= ½ teaspoon of bright red blood per episode) within 3 months prior to randomization.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Eli Lilly and Company: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

Carboplatin; Pemetrexed; Bevacizumab; cixutumumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. George Simon, Thoracic/Head & Neck Med Onc
• Organization: UT MD Anderson Cancer Center

GSIMON@MDANDERSON.ORG

713-794-4740

Study Officials

• George Simon, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2010
• First Posted: December 21, 2010
• Study Start: May 17, 2011
• Primary Completion: August 15, 2017
• Study Completion: August 15, 2017
• Last Updated: May 15, 2019
• Results First Posted: May 8, 2019

Record last verified: 2019-05

Locations

US (1)