MK2206 and Erlotinib Hydrochloride in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Progressed After Previous Response to Erlotinib Hydrochloride Therapy
Condition: Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma
MeSH terms: Carcinoma; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar
Intervention: Akt Inhibitor MK2206; Erlotinib Hydrochloride; Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given PO; Given PO; Correlative studies; Correlative studies
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well Akt inhibitor MK2206 (MK2206) and
      erlotinib hydrochloride works in treating patients with advanced non-small cell lung cancer
      who have progressed after previous response to erlotinib hydrochloride therapy. MK2206 and
      erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed non-small cell lung
             cancer of any histologic subtype

               -  NOTE: 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; however, 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; x-rays and/or scans for
             disease assessment of measurable disease must have been completed within 28 days prior
             to registration

          -  Patients must have radiologic or clinical progressive disease following prior benefit
             (response or stable disease) to EGFR-tyrosine kinase inhibitor (TKI) therapy (e.g.,
             erlotinib) administered either as a single agent or in combination with other agents
             for at least 12 weeks prior to progression; Note: patients may have received
             intervening systemic therapy after EGFR-TKI progression); additionally, patients must
             have documentation of radiographic progression within the preceding three months prior
             to study entry

          -  Prior cytotoxic chemotherapy is allowed; any number of prior chemotherapy regimens is
             also allowed; prior cetuximab therapy is also allowed; NOTE: a patient with an EGFR
             activating mutation who has received EGFR-TKI therapy as first line therapy, but has
             not received platinum-based chemotherapy, would be considered eligible for this trial

          -  Karnofsky performance status >= 60%

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelet count >= 100,000/mcL

          -  Total bilirubin =< upper institutional normal limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Creatinine =< upper institutional normal limits OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Prior to the first patient registration, this study must be institutional review board
             approved; a copy of the institutional review board (IRB) approval for each site
             involved must be given to the Data Coordinating Center at City of Hope

          -  Women of childbearing potential and men must use two forms of contraception (hormonal
             or barrier method of birth control; abstinence) prior to study entry and for the
             duration of study participation; should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, the patient should
             inform the treating physician immediately

          -  Patients on coumadin should have their international normalized ratio (INR) monitored
             at least once per week or more frequently depending on the investigator's judgment;
             there have been some case reports of increased INR when coumadin is co-administered
             with erlotinib

          -  Ability to understand and the willingness to sign a written informed consent document

          -  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

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have any ongoing
             grade 2 or greater toxicity from a prior treatment

          -  Patients may not be receiving any other investigational agents

          -  Patients with symptomatic brain metastases should be excluded from this clinical
             trial; 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 (mets) have been stopped for at least 14 days

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MK-2206 or erlotinib

          -  Caution must be observed for patients receiving any medications or substances that are
             strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4
             (CYP 450 3A4); although these patients are still potentially eligible, close
             monitoring is required for toxicity

          -  Preclinical studies demonstrated the potential of MK-2206 for induction of
             hyperglycemia in all preclinical species tested; patients with diabetes or in risk for
             hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia
             should be well controlled on oral agents before the patient enters the trial

          -  Preclinical studies indicated transient changes in corrected QT (QTc) interval during
             MK-2206 treatment; prolongation of QTc interval is potentially a safety concern while
             on MK-2206 therapy; cardiovascular: baseline Fridericia QT (QTcF) > 450 msec (male) or
             QTcF > 470 msec (female) will exclude patients from entry on study

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with this combination

          -  Human immunodeficiency (HIV)-positive patients on combination antiretroviral therapy
             are ineligible

          -  Prior MK-2206 therapy is not allowed

          -  Patients unable to swallow MK-2206 tablets and erlotinib tables whole are ineligible;
             (the tablets cannot be crushed or broken)