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



Status:Completed
Conditions:Lung Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:4/21/2016
Start Date:February 2011
End Date:August 2015

Use our guide to learn which trials are right for you!

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

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.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy (with the primary endpoint of disease control at 12 weeks) and
tolerability of the combination of MK2206 plus erlotinib (erlotinib hydrochloride) in
previously erlotinib-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-treated patients with
NSCLC who are treated with MK2206 plus erlotinib. II. To determine the overall survival of
previously erlotinib-treated patients with NSCLC who are treated with MK2206 plus erlotinib.

III. To assess the toxicity experienced by previously erlotinib-treated patients with NSCLC
treated with MK2206 plus erlotinib. 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-treated patients with NSCLC
treated with MK2206 plus erlotinib.

OUTLINE:

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.

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

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)
We found this trial at
7
sites
1500 E Duarte Rd
Duarte, California 91010
(626) 256-4673
City of Hope Comprehensive Cancer Center City of Hope is a leading research and treatment...
?
mi
from
Duarte, CA
Click here to add this to my saved trials
Beverly Hills, California 90211
?
mi
from
Beverly Hills, CA
Click here to add this to my saved trials
5841 S Maryland Ave
Chicago, Illinois 60637
1-773-702-6180
University of Chicago Comprehensive Cancer Center The University of Chicago Comprehensive Cancer Center (UCCCC) is...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
1441 Eastlake Ave
Los Angeles, California 90033
(323) 865-3000
U.S.C./Norris Comprehensive Cancer Center The USC Norris Comprehensive Cancer Center, located in Los Angeles, is...
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
Pittsburgh, Pennsylvania 15232
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
?
mi
from
Sacramento, CA
Click here to add this to my saved trials
South Pasadena, California 91030
?
mi
from
South Pasadena, CA
Click here to add this to my saved trials