MK2206 and Erlotinib Hydrochloride in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Progressed After Previous Response to Erlotinib Hydrochloride Therapy

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of any histologic subtype

  • Epidermal growth factor receptor (EGFR) mutational status (either wild-type or positive for an activating mutation)will be determined for all patients on this study

    • Commercial assays for EGFR mutation status are allowed
  • Knowledge of EGFR mutational status is not required at the time of protocol entry but should be determined or known before the end of course 2
  • If one of the strata is temporarily closed to accrual, knowledge of EGFR mutational status will be required prior to protocol entry
• Patients may have measurable or non-measurable disease

• Patients must have radiological or clinical progressive disease following prior benefit(response or stable disease) to EGFR-TKI therapy (e.g., erlotinib hydrochloride) administered either as a single agent or in combination with other agents for at least 12 weeks prior to progression

  • Patients may have received intervening systemic therapy after EGFR-TKI progression
• Patients must have documentation of radiographic progression within the preceding three months prior to study entry

• Patients should have tumor tissue (either fresh-frozen tumor tissue or paraffin-embedded tumor tissue) available for retrieval

  • If an endobronchial lesion is present or suspected, bronchoscopy is recommended as a source of fresh tissue
  • Tissue blocks or unstained slides from the time of original diagnosis are acceptable if repeat biopsy is not feasible

• No patients with symptomatic brain metastases

  • Patients with asymptomatic controlled or treated (e.g., with radiation and/or surgery)brain metastases are otherwise eligible as long as corticosteroids given expressly for brain metastases have been stopped for at least 14 days
• Karnofsky performance status 60-100%
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Total bilirubin less than or equal to upper institutional normal limits
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine less than or equal to upper institutional normal limits OR creatinine clearance ≥ 60 mL/min
• Women of childbearing potential and men must use two forms of contraception (hormonal, barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation
• Not pregnant or nursing
• Negative pregnancy test
• Patients with diabetes or in risk for hyperglycemia should have well-controlled glycemic levels on oral agents before entering the trial
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to Akt inhibitor MK2206 (MK2206) or erlotinib hydrochloride
• No baseline QTcF > 450 msec (male) or QTcF > 470 msec (female)
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness and/or social situations that would limit compliance with study requirements

• Must be able to swallow MK2206 and erlotinib hydrochloride tablets whole

  • The tablets cannot be crushed or broken
• No concurrent combination antiretroviral therapy for HIV-positive patients
• Prior cytotoxic chemotherapy is allowed
• Any number of prior chemotherapy regimens is also allowed
• Prior cetuximab therapy is allowed
• Patient with an EGFR-activating mutation who has received prior EGFR-TKI therapy as first-line therapy, but has not received platinum-based chemotherapy, would be considered eligible for this trial
• More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and no ongoing grade 2 or greater toxicity from a prior treatment
• No prior Akt inhibitor MK2206
• No other concurrent investigational agents