BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Erlotinib; AZD6244; MK-2206; Sorafenib; Erlotinib; MK-2206
Intervention description: 150 mg by mouth each day of a 28 day cycle.; 100 mg by mouth daily of a 28 day cycle.; 100 mg by mouth every week of a 28 day cycle.; 400 mg by mouth twice a day for a 28 day cycle.; 150 mg by mouth daily of a 28 day cycle.; 135 mg by mouth every week of a 28 day cycle.
Intervention MeSH terms: Erlotinib Hydrochloride; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 334.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non small cell lung cancer; Biopsy accessible tumor; Stage IIIB non small cell lung cancer; Stage IV non small cell lung cancer

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. The subject has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or
             fine-needle aspiration.

          2. 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).

          3. The subject has measurable NSCLC (patients with active new disease growth in
             previously irradiated site are eligible).

          4. The subject's ECOG performance status is </= 2 at study entry.

          5. The subject has biopsy accessible tumor

          6. 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.

          7. 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.

          8. Serum creatinine clearance >50ml/min, either by Cockcroft-Gault formula or 24-hour
             urine collection analysis

          9. If subject has brain metastasis, they must have been stable (treated and/or
             asymptomatic) and off steroids for at least 2 weeks.

         10. The subject is >/=18 years of age.

         11. The subject has signed informed consent.

         12. 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.

         13. 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.

         14. 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.

         15. 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.

        Exclusion Criteria:

          1. 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).

          2. The subject has undergone prior thoracic or abdominal surgery within 30 days of study
             entry, excluding prior diagnostic biopsy.

          3. 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).

          4. The subject has neuropathy >/= grade 2

          5. 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.

          6. 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).

          7. Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory
             bowel disease), or significant bowel resection that would preclude adequate absorption

          8. Subjects with poorly controlled diabetes (HbA1c >8%) are excluded.

          9. Subjects whose tumor harbors the EML4-ALK fusion gene are excluded unless the patient
             has failed treatment with Anaplastic Lymphoma Kinase (ALK) inhibitor.

         10. 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.

         11. 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.

         12. 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.

         13. 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.