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Akt Inhibitor MK2206 in Treating Patients With Advanced Gastric or Gastroesophageal Junction Cancer

A Phase II Study of MK-2206 (NSC-749607) as Second Line Therapy for Advanced Gastric and Gastroesophageal Junction Cancer

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01260701
Enrollment
75
Registered
2010-12-15
Start date
2011-01-31
Completion date
2015-07-31
Last updated
2016-01-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adenocarcinoma of the Gastroesophageal Junction, Diffuse Gastric Adenocarcinoma, Gastric Intestinal Type Adenocarcinoma, Gastric Mixed Adenocarcinoma, Recurrent Gastric Carcinoma

Brief summary

This phase II clinical trial studies how well Akt inhibitor MK2206 works in treating patients with advanced gastric or gastroesophageal junction cancer. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the overall survival (OS) for patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma treated with MK-2206 (Akt inhibitor MK2206). SECONDARY OBJECTIVES: I. To estimate the progression free survival (PFS) in this patient population. II. To estimate the response rate (confirmed and unconfirmed complete response \[CR\] and partial response \[PR\] by Response Evaluation Criteria In Solid Tumors \[RECIST\] 1.1) in this patient population. III. To assess the frequency and severity of toxicity associated with this regimen. OUTLINE (CLOSED TO ACCRUAL 05/01/13): Patients receive Akt inhibitor MK2206 orally (PO) every other day 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 3 months for 2 years.

Interventions

DRUGAkt Inhibitor MK2206

Given PO

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Patients must have histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal (GE) junction that has progressed after first-line treatment, or is recurrent within 6 months after receiving adjuvant therapy; patients must have had exactly one prior systemic treatment regimen; previous adjuvant (chemotherapy \[chemo\]) radiotherapy is permitted; prior chemotherapy given concurrently with radiation for radiosensitization is not considered one prior systemic regimen * Patients must have measurable disease; computed tomography (CT) scans or magnetic resonance imaging (MRIs) used to assess measurable disease must have been completed within 28 days prior to registration; CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1) * Patients must not have known brain metastases * Patients must not have received chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration * Patient must not have received prior treatment with a phosphatidylinositol 3 (PI3), v-akt murine thymoma viral oncogene homolog 1 (AKT) or mechanistic target of rapamycin (Mtor) inhibitor for any reason * All toxicities from prior therapy must have resolved to =\< grade 1 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 4.0) prior to registration * Patients must not be receiving or planning to receive any other investigational agents * Patients must be able to tolerate oral medications and must not have malabsorption or chronic diarrhea (CTCAE version 4.0 grade 2 or higher); administration through a feeding tube is not permitted * Hemoglobin \>= 9 g/dL * Absolute neutrophil count (ANC) \>= 1,500/mcL * Platelets \>= 100,000/mcL * Total bilirubin =\< institutional upper limit of normal (IULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =\< 2.5 x IULN; patients with liver metastases must have AST and ALT =\< 5 x IULN * Patients must have adequate kidney function as evidenced by at least ONE of the following: * Serum creatinine (mg/dL) =\< IULN obtained within 14 days prior to registration * Calculated creatinine clearance \> 50 ml/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to registration * Patients must have international normalized ratio (INR) =\< 1.2 unless taking therapeutic doses of warfarin; this result must be obtained within 14 days prior to registration * Patients must have fasting blood sugar =\< 150 mg/dL within 28 days prior to registration * Patients must have hemoglobin A1C \< 7% within 28 days prior to registration * Patients must have an electrocardiogram (ECG) within 28 days prior to registration; patients must have corrected QT interval (QTcF) (by Fridericia's calculation) \< 450 msec (male) or \< 470 msec (female) * Patients must have a Zubrod performance status of 0-1 * Patient must not have any of the following: a history of congenital long QT syndrome; use of concomitant medications that could prolong the QTc interval; New York Heart Association class III or IV heart failure; history of myocardial infarction within 6 months prior to registration; uncontrolled dysrhythmias; poorly controlled angina; resting heart rate =\< 50 bpm (bradycardia) * Patients must not be receiving concurrent treatment with drugs that are strong inducers or inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4); patients must be able to safely discontinue treatment with these agents for \>= 2 weeks prior to beginning protocol therapy * Patient must not have 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 * Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible * Patient must not be pregnant or nursing; women/men of reproductive potential must have agreed to use two forms of contraception for the duration of protocol treatment and for one month after discontinuation of MK-2206; a woman is considered to be of reproductive potential if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, effective contraception also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any time a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years * All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Design outcomes

Primary

MeasureTime frameDescription
Overall Survival (OS)Up to 2 yearsOverall survival is calculated from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Secondary

MeasureTime frameDescription
Progression Free Survival (PFS)Up to 2 yearsPFS is measured from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and without report of progression are censored at date of last contact. Progression is one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy), as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Response Rate (Complete and Partial, Confirmed and Unconfirmed)Up to 2 yearsComplete response (CR) is complete disappearance of all target and non-target lesions, no new lesions, and no disease related symptoms. Any lymph nodes must have reduction in short axis to \< 1.0 cm. Partial response (PR) is \>= 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions. Confirmed CR is two or more statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Confirmed PR is two or more statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration, but not qualifying as CR. Unconfirmed CR is one status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugUp to 2 yearsAny CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were possibly, probably or definitely related to protocol treatment are included.

Countries

Canada, United States

Participant flow

Participants by arm

ArmCount
MK-2206
Patients receive Akt inhibitor MK-2206 PO QD, every other day, for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
70
Total70

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyAdverse Event9
Overall StudyDeath2
Overall StudyDid not begin protocol therapy1
Overall StudyIneligible4
Overall StudyNot protocol specified3
Overall StudyProgression53
Overall StudyUnder review1
Overall StudyWithdrawal by Subject2

Baseline characteristics

CharacteristicMK-2206
Age, Continuous60 years
Ethnicity (NIH/OMB)
Hispanic or Latino
13 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
56 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
Race/Ethnicity, Customized
Asian
5 participants
Race/Ethnicity, Customized
Unknown
3 participants
Race/Ethnicity, Customized
White
62 participants
Sex: Female, Male
Female
21 Participants
Sex: Female, Male
Male
49 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
67 / 70
serious
Total, serious adverse events
31 / 70

Outcome results

Primary

Overall Survival (OS)

Overall survival is calculated from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Time frame: Up to 2 years

Population: Eligible patients who began protocol therapy.

ArmMeasureValue (MEDIAN)
MK-2206Overall Survival (OS)5 months
Secondary

Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug

Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were possibly, probably or definitely related to protocol treatment are included.

Time frame: Up to 2 years

Population: Eligible patients who received any treatment and were assessed for adverse events are included in this summary.

ArmMeasureGroupValue (NUMBER)
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugAdult respiratory distress syndrome1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugAlanine aminotransferase increased1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugAlkaline phosphatase increased2 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugAllergic reaction1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugAnemia3 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugAnorexia3 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugAspartate aminotransferase increased1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugBlood and lymphatic system disorders - Other1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugBlood bilirubin increased1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugCardiac arrest1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugDehydration1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugDyspnea1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugFatigue4 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugGastric hemorrhage1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugGastroesophageal reflux disease1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugHyperglycemia2 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugHypokalemia1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugHyponatremia2 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugHypoxia1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugLung infection1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugLymphocyte count decreased1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugNausea1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugNon-cardiac chest pain1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugPleural effusion2 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugPneumonitis1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugPruritus1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugRash acneiform2 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugRash maculo-papular2 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugRespiratory failure1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugSinus bradycardia1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugSinus tachycardia1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugStroke1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugUpper gastrointestinal hemorrhage1 Participants
MK-2206Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugVomiting2 Participants
Secondary

Progression Free Survival (PFS)

PFS is measured from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and without report of progression are censored at date of last contact. Progression is one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy), as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.

Time frame: Up to 2 years

Population: Eligible patients who began protocol therapy

ArmMeasureValue (MEDIAN)
MK-2206Progression Free Survival (PFS)1.8 months
Secondary

Response Rate (Complete and Partial, Confirmed and Unconfirmed)

Complete response (CR) is complete disappearance of all target and non-target lesions, no new lesions, and no disease related symptoms. Any lymph nodes must have reduction in short axis to \< 1.0 cm. Partial response (PR) is \>= 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions. Confirmed CR is two or more statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Confirmed PR is two or more statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration, but not qualifying as CR. Unconfirmed CR is one status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

Time frame: Up to 2 years

Population: Eligible patients who began protocol therapy and were assessed for response.

ArmMeasureValue (NUMBER)
MK-2206Response Rate (Complete and Partial, Confirmed and Unconfirmed)1.5 percentage of participants

Source: ClinicalTrials.gov · Data processed: Mar 8, 2026