BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer

NCT01248247 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 2009-0360P01 CA148133NCI-2011-01104
• Study Type: interventional
• Target: 334
• Locations: 1 country
• Sites: 2

Brief Summary

Different people have different biomarkers (chemical "markers" in the blood that may be related to your reaction to study drugs). If researchers know about your biomarkers before you receive treatment, they may be able to prescribe a treatment that is better suited to your body's specific needs. The goal of this clinical research study is to learn if drug or drug combinations based on your biomarkers can help to control NSCLC. The safety of these drug combinations will also be studied.

Conditions

Lung Cancer

Keywords

Non small cell lung cancer; Biopsy accessible tumor; Stage IIIB non small cell lung cancer; Stage IV non small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• 8-Week Disease Control Rate (DCR)

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: 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.

  8 weeks

Secondary Outcomes (1)

• Median Progression-free Survival

  From the date of drug start to the earliest sign of disease progression or death

Study Arms (4)

Group 1 - Erlotinib

EXPERIMENTAL

Erlotinib 150 mg by mouth each day of a 28 day cycle.

Drug: Erlotinib

Group 2 - Erlotinib + MK-2206

EXPERIMENTAL

Erlotinib 150 mg by mouth each day of a 28 day cycle. MK-2206 135 mg by mouth every week of a 28 day cycle.

Drug: Erlotinib; Drug: MK-2206

Group 3 - AZD6244 + MK-2206

EXPERIMENTAL

AZD6244 100 mg by mouth daily of a 28 day cycle. MK-2206 100 mg by mouth every week of a 28 day cycle.

Drug: AZD6244; Drug: MK-2206

Group 4 - Sorafenib

EXPERIMENTAL

Sorafenib 400 mg by mouth twice a day for a 28 day cycle.

Drug: Sorafenib

Interventions

Erlotinib DRUG

150 mg by mouth each day of a 28 day cycle.

Also known as: OSI-774, Tarceva

Group 1 - Erlotinib

AZD6244 DRUG

100 mg by mouth daily of a 28 day cycle.

Group 3 - AZD6244 + MK-2206

MK-2206 DRUG

100 mg by mouth every week of a 28 day cycle.

Group 3 - AZD6244 + MK-2206

Sorafenib DRUG

400 mg by mouth twice a day for a 28 day cycle.

Also known as: Nexavar, BAY43-9006

Group 4 - Sorafenib

Eligibility Criteria

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

You may qualify if:

• The subject has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration.
• The subject has a diagnosis of either advanced, incurable stage IIIB or stage IV NSCLC, and failed at least one front-line metastatic NSCLC chemotherapy regimen, or EGFR TKI. (Subjects who have failed adjuvant or locally advanced therapy within 6 months are also eligible to participate in the study).
• The subject has measurable NSCLC (patients with active new disease growth in previously irradiated site are eligible).
• The subject's ECOG performance status is \</= 2 at study entry.
• The subject has biopsy accessible tumor
• The subject has adequate hematologic function as defined by an absolute neutrophil count (ANC) \>/= 1,500/mm3, platelet count \>/= 100,000/mm3, WBC \>/= 3,000/ mm3, and hemoglobin \>/= 9 g/dL.
• The subject has adequate hepatic function as defined by a total bilirubin level \</= 1.5 x the upper limit of normal (ULN) (bilirubin \>/= 1.5 x ULN with 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.
• Serum creatinine clearance \>50ml/min, either by Cockcroft-Gault formula or 24-hour urine collection analysis
• If subject has brain metastasis, they must have been stable (treated and/or asymptomatic) and off steroids for at least 2 weeks.
• The subject is \>/=18 years of age.
• The subject has signed informed consent.
• The subject is eligible if disease free from a previously treated malignancy, other than a previous NSCLC, for greater than two years. Subject with a history of prior basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix are allowed.
• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 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 subject, if a man, agrees to use effective contraception or abstinence while on study and for 90 days after last dose of study drug.
• Subject is able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis.

You may not qualify if:

• The subject has received prior chemotherapy, surgery, or radiotherapy within 3 weeks of initiating study drug, or 4 weeks for bevacizumab or investigational drug or 72 hours for erlotinib or the subject has not recovered (\</= Grade 1) from side effects of the prior therapy (localized palliative radiotherapy within 2 weeks is allowed).
• The subject has undergone prior thoracic or abdominal surgery within 30 days of study entry, excluding prior diagnostic biopsy.
• The subject has cardiac conditions as follows: uncontrolled hypertension BP \> 140/90 despite optimal therapy, uncontrolled angina, ventricular arrhythmias, or congestive heart failure New York Heart Association Class II or above, baseline LVEF \</= 50%, prior or current cardiomyopathy, atrial fibrillation with heart rate \>100 bpm, unstable ischaemic heart disease (MI within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly).
• The subject has neuropathy \>/= grade 2
• The subject is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding. In the event of inconclusive pregnancy test results, the investigator will have final determination of pregnancy status.
• Subjects will be excluded for other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver or renal disease).
• Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
• Subjects with poorly controlled diabetes (HbA1c \>8%) are excluded.
• Subjects whose tumor harbors the EML4-ALK fusion gene are excluded unless the patient has failed treatment with Anaplastic Lymphoma Kinase (ALK) inhibitor.
• Subjects are excluded if they have QTc prolongation \>450 msec (Bazett's Formula) for males or \>470 ms for females on screening or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class II or above or require use of a concomitant medication that can prolong the QT interval.
• Subjects who have abnormal K+ or Mg++ levels will be excluded if these levels cannot be corrected to within normal range with adequate supportive treatment prior to study drug initiation.
• Subjects whose tumor harbors an EGFR mutation are excluded unless the subject failed treatment with EGFR TKIs in which case the subject can be randomized to Arms 2, 3, and 4.
• Drug Specific Eligibility Criteria based on Treatment Arms- Subjects are excluded from the erlotinib monotherapy arm if they have progressed on prior EGFR TKI therapy; from the AKT inhibitor arm(s) if they have received prior AKT inhibitor therapy; from the MEK inhibitor arm if they have received prior MEK inhibitor therapy; and from Sorafenib arm if they have previously received the drug or have prior history of clinically significant hemoptysis or bleeding diathesis as per principal investigator judgment.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator
• GlaxoSmithKline: collaborator
• Novartis: collaborator

Study Sites (2)

Yale Universtiy

New Haven, Connecticut, 06520, United States

Location

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

Interventions

Erlotinib Hydrochloride; AZD 6244; MK 2206; Sorafenib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Marcelo Vailati Negrao, MD, Assistant Professor, Thoracic-Head & Neck Med Onc
• Organization: UT MD Anderson Cancer Center

mvnegrao@mdanderson.org

(713) 614-4938

Study Officials

• Marcelo V. Negrao, 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: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2010
• First Posted: November 25, 2010
• Study Start: June 2, 2011
• Primary Completion: November 30, 2020
• Study Completion: November 30, 2020
• Last Updated: January 12, 2022
• Results First Posted: January 12, 2022

Record last verified: 2021-12

Locations

US (2)