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

NCT01294306 | Completed Phase 2 Results DMC

• 9 other identifiers: NCI-2011-02578CDR0000695056CHNMC-PHII-108PhII-1088698N01CM00038N01CM00071N01CM62209P30CA033572
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (2)

• Disease-control Rate

  Disease-control rate defined as response rate + stable disease at 12 weeks. Stable disease must have been achieved for 12 weeks or longer. Response evaluated 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; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

  At 12 weeks

• Objective Response

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response = CR + PR

  Up to 2 years

Secondary Outcomes (3)

• Median Progression-free Survival

  Up to 2 years

• Toxicity of Akt Inhibitor MK2206 Plus Erlotinib Hydrochloride

  Time Frame: Up to 2 years

• Median Overall Survival

  Up to 2 Years

Study Arms (1)

Treatment (Akt inhibitor MK2206, erlotinib hydrochloride)

EXPERIMENTAL

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.

Drug: Akt Inhibitor MK2206; Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Akt Inhibitor MK2206 DRUG

Given PO

Also known as: MK2206

Treatment (Akt inhibitor MK2206, erlotinib hydrochloride)

Erlotinib Hydrochloride DRUG

Given PO

Also known as: Cp-358,774, OSI-774, Tarceva

Treatment (Akt inhibitor MK2206, erlotinib hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Akt inhibitor MK2206, erlotinib hydrochloride)

Pharmacological Study OTHER

Correlative studies

Treatment (Akt inhibitor MK2206, erlotinib hydrochloride)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

Tower Cancer Research Foundation

Beverly Hills, California, 90211-1850, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Adenocarcinoma, Bronchiolo-Alveolar; Adenocarcinoma of Lung; Carcinoma, Non-Small-Cell Lung

Interventions

MK 2206; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: DCC Project Administrator
• Organization: California Cancer Consortium

CCCP@coh.org

626-256-4673

Study Officials

• Primo Lara

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2011
• First Posted: February 11, 2011
• Study Start: February 1, 2011
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: November 29, 2016
• Results First Posted: October 17, 2016

Record last verified: 2016-10

Locations

US (7)