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

Adenocarcinoma of the Gastroesophageal Junction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01260701
• Other study ID #: NCI-2011-02619
• Secondary ID: NCI-2011-02619SW
• Status: Completed
• Phase: Phase 2
• First received: December 14, 2010
• Last updated: December 14, 2015
• Start date: January 2011
• Est. completion date: July 2015

Study information

• Verified date: November 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: July 2015
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Diffuse Gastric Adenocarcinoma
• Esophageal Neoplasms
• Gastric Intestinal Type Adenocarcinoma
• Gastric Mixed Adenocarcinoma
• Recurrent Gastric Carcinoma
• Stomach Neoplasms

Intervention

Drug:
• Akt Inhibitor MK2206
Given PO

Locations

Country	Name	City	State
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
United States	Oncare Hawaii Inc-Pali Momi	Aiea	Hawaii
United States	Pali Momi Medical Center	Aiea	Hawaii
United States	Akron General Medical Center	Akron	Ohio
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Michigan Cancer Research Consortium CCOP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Randolph Hospital	Asheboro	North Carolina
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Franciscan St. Francis Health-Beech Grove	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Frontier Cancer Center and Blood Institute-Billings	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Columbus CCOP	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Dayton CCOP	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Cadence Cancer Center at Delnor	Geneva	Illinois
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Saint Rose Ambulatory and Surgery Center	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Hays Medical Center	Hays	Kansas
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Oncare Hawaii Inc-Kuakini	Honolulu	Hawaii
United States	Oncare Hawaii Inc-POB II	Honolulu	Hawaii
United States	OnCare Hawaii-Liliha	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	Baylor Saint Luke's Medical Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Michael E DeBakey VA Medical Center	Houston	Texas
United States	Hutchinson Regional Medical Center	Hutchinson	Kansas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Franciscan Saint Francis Health-Indianapolis	Indianapolis	Indiana
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	Fowler Family Center for Cancer Care	Jonesboro	Arkansas
United States	NEA Baptist Memorial Hospital	Jonesboro	Arkansas
United States	Castle Medical Center	Kailua	Hawaii
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kansas City Cancer Center - South	Kansas City	Missouri
United States	Kansas City Cancer Centers - North	Kansas City	Missouri
United States	The University of Kansas Cancer Center-West	Kansas City	Kansas
United States	Truman Medical Center	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Kettering Medical Center	Kettering	Ohio
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	EvergreenHealth Medical Center	Kirkland	Washington
United States	Seattle Cancer Care Alliance at EvergreenHealth	Kirkland	Washington
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Kansas City Cancer Center-Lee's Summit	Lee's Summit	Missouri
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Memorial Hospital Of Martinsville	Martinsville	Virginia
United States	Loyola University Medical Center	Maywood	Illinois
United States	Winthrop University Hospital	Mineola	New York
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Providence Hospital	Mobile	Alabama
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	Kansas City Cancer Centers-Southwest	Overland Park	Kansas
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Via Christi Hospital-Pittsburg	Pittsburg	Kansas
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Oregon Health and Science University	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Reid Hospital and Health Care Services	Richmond	Indiana
United States	Interlakes Foundation Inc-Rochester	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Saint Louis University Hospital	Saint Louis	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	Memorial University Medical Center	Savannah	Georgia
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Cooperative of Puget Sound Oncology Consortium	Seattle	Washington
United States	Group Health Cooperative-Seattle	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Medical Center-First Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	The Polyclinic	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Virginia Mason CCOP	Seattle	Washington
United States	United General Hospital	Sedro-Woolley	Washington
United States	Kansas City Cancer Center-Shawnee Mission	Shawnee Mission	Kansas
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Rockwood Clinic	Spokane	Washington
United States	Cancer Research for the Ozarks NCORP	Springfield	Missouri
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	The University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	The University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona
United States	The University of Arizona Medical Center-University Campus	Tucson	Arizona
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Cadence Cancer Center in Warrenville	Warrenville	Illinois
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Main Office	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita CCOP	Wichita	Kansas
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Southeast Cancer Control Consortium CCOP	Winston-Salem	North Carolina
United States	Metro Health Hospital	Wyoming	Michigan
United States	Greene Memorial Hospital	Xenia	Ohio
United States	Genesis HealthCare System	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to 2 years	No
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.	Up to 2 years	No
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.	Up to 2 years	No
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.	Up to 2 years	Yes