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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01294306
First received: February 10, 2011
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

This phase II trial studies the side effects and how well 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.


Condition Intervention Phase
Adenocarcinoma of the Lung
Adenosquamous Cell Lung Cancer
Bronchoalveolar Cell Lung Cancer
Large Cell Lung Cancer
Recurrent Non-small Cell Lung Cancer
Squamous Cell Lung Cancer
Drug: Akt inhibitor MK2206
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of the Akt Inhibitor MK-2206 Plus Erlotinib (OSI-774) in Patients With Advanced Non-Small Cell Lung Cancer Who Have Progressed After Previous Response (Including Stable Disease) With Erlotinib Therapy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response of patients with EGFR mutation as defined by RECIST (stratum 1) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Disease-control rate (DCR: response rate + stable disease) in patients with EGFR wild-type tumor (stratum 2) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity of MK2206 plus erlotinib hydrochloride, graded according to NCI CTCAE v. 4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    The type, severity, time of onset, duration, and outcome of toxicities will be summarized.

  • Progression-free survival rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Summarized with Kaplan-Meier plots.

  • Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Summarized with Kaplan-Meier plots.


Estimated Enrollment: 90
Study Start Date: February 2011
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (Akt inhibitor MK2206)

Patients receive Akt inhibitor MK2206 PO QOD of a 28-day course, and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during study for pharmacokinetics and correlative studies.

Drug: Akt inhibitor MK2206
Given PO
Other Name: MK2206
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy (with the primary endpoint of disease control at 12 weeks) and tolerability of the combination of Akt inhibitor MK2206 (MK2206) plus erlotinib hydrochloride in previously erlotinib hydrochloride-treated patients with recurrent or progressive advanced non-small cell lung cancer (NSCLC) whose tumors are either epidermal growth factor receptor (EGFR) mutated or EGFR wild-type.

SECONDARY OBJECTIVES:

I. To determine progression-free survival of previously erlotinib hydrochloride-treated patients with NSCLC who are treated with MK2206 plus erlotinib hydrochloride. II. To determine the overall survival of previously erlotinib hydrochloride-treated patients with NSCLC who are treated with MK2206 plus erlotinib hydrochloride.

III. To assess the toxicity experienced by previously erlotinib hydrochloride-treated patients with NSCLC treated with MK2206 plus erlotinib hydrochloride. IV. To perform correlative analysis of tumor biomarkers to assess, in a preliminary manner, the association between tumor mutations and/or abnormalities and clinical outcome of previously erlotinib hydrochloride-treated patients with NSCLC treated with MK2206 plus erlotinib hydrochloride.

OUTLINE: This is a multicenter study. Patients are stratified according to epidermal growth factor receptor (EGFR) status (mutated vs wild-type).

Patients receive Akt inhibitor MK2206 orally (PO) every other day (QOD) of a 28-day course, and erlotinib hydrochloride PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during study for pharmacokinetics and correlative studies.

After completion of study therapy, patients are followed up every 12 weeks for one year then annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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; x-rays and/or scans for disease assessment of measurable disease must have been completed within 28 days prior to registration
  • 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 radiologic or clinical progressive disease following prior benefit (response or stable disease) to EGFR-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 glutamic 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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; 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 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 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 QTc interval during MK-2206 treatment; prolongation of QTc interval is potentially a safety concern while on MK-2206 therapy; cardiovascular: baseline 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 because MK-2206 and erlotinib are anti-cancer agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MK-2206 and erlotinib, breastfeeding should be discontinued if the mother is treated with this combination
  • Human immunodeficiency (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MK-2206 plus erlotinib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01294306

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
City of Hope
Duarte, California, United States, 91010
University of Southern California/Norris Cancer Center
Los Angeles, California, United States, 90033
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Investigators
Principal Investigator: Primo Lara Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01294306     History of Changes
Other Study ID Numbers: NCI-2011-02578, NCI-2011-02578, CDR0000695056, P30CA033572, N01CM00038, N01CM00071, CHNMC-PHII-108, PHII-108, 8698, N01CM00071, N01CM00038, P30CA033572
Study First Received: February 10, 2011
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Adenocarcinoma, Bronchiolo-Alveolar
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014