Clinical And Translational Study Of MK-2206 In Patients With Metastatic KRAS-Wild-Type, PIK3CA-Mutated, Colorectal Cancer

NCT01186705 | Terminated Phase 2 Results DMC

• 1 other identifier: 10-068
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test a new drug called MK-2206 for metastatic colorectal cancer. This drug is being tested in a subgroup of patients with colorectal cancer whose tumors have changes in certain genes that may make them more likely to respond to this new medication. As tumors develop, the cells within the tumor acquire mutations within genes, allowing them to grow more effectively. We will be testing your tumor for mutations involving two genes - KRAS and PIK3CA. Patients whose tumors have a normal copy of the KRAS gene and a mutation within the PIK3CA gene will be eligible to participate in this study. This study is a phase 2 study. The goal of a phase 2 study is to find out what effects, good and/or bad, a new treatment has against a certain type of cancer.

Conditions

Colon Cancer; Rectal Cancer

Keywords

MK-2206; colon; rectal; 10-068

Outcome Measures

Primary Outcomes (1)

• Overall Objective Response Rate (ORR)

  in patients with metastatic colorectal cancer with known PIK3CA mutations and wild type KRAS, to single agent MK-2206. Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1)

  1 year

Study Arms (1)

MK-2206

EXPERIMENTAL

This will be a single-arm, phase II study of the AKT inhibitor MK-2206 in patients with KRAS-wild-type, PIK3CA-mutated, colorectal cancer whose tumors have progressed through standard chemotherapy regimens.

Drug: MK-2206

Interventions

MK-2206 DRUG

Patients will receive MK-2206 orally in a once weekly dose of 200mg. There will be no dose escalation. Patients will be treated until disease progression or unacceptable side effects.

MK-2206

Eligibility Criteria

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

You may qualify if:

• Patient must have metastatic colorectal cancer that has been histologically or cytologically-confirmed at MSKCC and has failed to respond to appropriate standard therapy regimens. There is no limit on the number of prior treatment regimens permitted.
• Patient is male or female and ≥18 years of age on the day of signing informed consent.
• Patient must have performance status of 0 or 1 on the ECOG Performance Scale.
• Patient must have adequate organ function as indicated by the following laboratory values:
• Absolute neutrophil count (ANC) ≥1,500 /μL
• Platelets ≥100,000 /μL
• Hemoglobin ≥9 g/dL
• Serum creatinine or calculated creatinine clearance ≤1.5 x upper limit of normal (ULN) OR ≥60 mL/min for patients with creatinine levels \>1.5 x institutional ULN
• Serum total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels \>1.5 x ULN
• AST (SGOT) and ALT (SGPT) ≤3 x ULN or ≤5 x ULN in patients with known liver metastasis
• Prothrombin time (PT)/INR ≤1.5 x ULN
• Partial thromboplastin time (PTT)≤1.5 x ULN
• Fasting serum glucose ≤120 mg/dl
• HBA1C ≤8%
• Potassium in normal range

You may not qualify if:

• Patient who has had chemotherapy, radiotherapy, or biological therapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C), or who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1.
• Patients must be at least 4 weeks post major surgical procedure, and all surgical wounds must be fully healed.
• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of Study Day 1.
• Patient has known CNS metastases and/or carcinomatous meningitis.
• Patient has a primary central nervous system tumor.
• Patient has known hypersensitivity to the components of study drug or its analogs.
• Patient has a history or current evidence of clinically significant heart disease including:
• Clinically significant congestive heart failure, unstable angina pectoris,
• Clinically significant cardiac arrhythmia,
• History or current evidence of a myocardial infarction during the last 6 months, and/or a current ECG tracing that is abnormal in the opinion of the treating Investigator,
• QTc prolongation ≥450 msec (Bazett's Formula), Patient with evidence of clinically significant bradycardia (HR \<50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2).
• Patient with uncontrolled hypertension (i.e., \> 160/90 mHg SiBP). Patients who are controlled on antihypertensive medication will be allowed to enter the study.
• Patient at significant risk for hypokalemia (e.g., patients on high dose diuretics, or with recurrent diarrhea)
• Patient with poorly controlled diabetes (HBA1C \>8%)
• Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

MK 2206

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Dr. Leonard Saltz
• Organization: Memorial Sloan Kettering Cancer Center

saltzl@mskcc.org

646-888-4286

Study Officials

• Leonard Saltz, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: August 20, 2010
• First Posted: August 23, 2010
• Study Start: August 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: November 18, 2015
• Results First Posted: April 21, 2015

Record last verified: 2015-10

Locations

US (1)