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Study of MK-2206 in Patients With Metastatic Neuroendocrine Tumors (NET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01169649
Recruitment Status : Completed
First Posted : July 26, 2010
Results First Posted : February 18, 2016
Last Update Posted : February 18, 2016
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE July 21, 2010
First Posted Date  ICMJE July 26, 2010
Results First Submitted Date  ICMJE April 8, 2015
Results First Posted Date  ICMJE February 18, 2016
Last Update Posted Date February 18, 2016
Study Start Date  ICMJE July 2010
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 21, 2016)
Overall Response. [ Time Frame: every 12 weeks ]
Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Original Primary Outcome Measures  ICMJE
 (submitted: July 22, 2010)
To assess overall response. [ Time Frame: every 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2010)
  • To evaluate the safety. [ Time Frame: Will be assessed weekly for first six weeks. Will then be assessed every other week, on treatment weeks only. ]
    Safety will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0, based on recorded adverse events, physical examinations, and clinical laboratory assessments.
  • To evaluate tolerability. [ Time Frame: Will be assessed weekly for first six weeks. Will then be assessed every other week, on treatment weeks only. ]
  • To evaluate adverse event profiles. [ Time Frame: Will be assessed weekly for first six weeks. Will then be assessed every other week, on treatment weeks only. ]
  • To evaluate tumors for expression for putative markers along the PI3K pathway. [ Time Frame: 2 years ]
    Archival tissue will be tested for genotype and mutational status of PI3K, and BRAF in stages 1 and 2.
  • To assess overall survival. [ Time Frame: every three months until death, or the cut-off date for the last protocol mandated analysis, whichever occurs first. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of MK-2206 in Patients With Metastatic Neuroendocrine Tumors (NET)
Official Title  ICMJE A Phase II Clinical and Translational Study of MK-2206 in Patients With Metastatic Neuroendocrine Tumors (NET)
Brief Summary

The purpose of this study is to test a new drug called MK-2206. This study is a phase II study. In cancer studies, a phase II study is to find out what effects, good and/or bad, a new treatment has against a certain type of cancer.

MK-2206 is an oral medication known as a targeted therapy. By attaching to the target, we hope that MK-2206 may stop the cancer cells from further growth and dividing. This study will help find out if MK-2206 is a helpful drug when taken in patients with neuroendocrine tumor.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • PANCREAS
  • Neuroendocrine
Intervention  ICMJE Drug: MK-2206
MK-2206 will be given orally 200 mg qw as given in the prior Ph1 clinical trial that demonstrated safety, tolerability and adequate PK/PD values at this dose. Follow-up imaging scans will be performed every 12 weeks to evaluate response. Patients must take MK-2206 orally at least 2 hours before or 2 hours after food or a meal.
Study Arms  ICMJE Experimental: islet cell carcinomas and carcinoid tumors
This is an open label phase II study of MK-2206 administered to patients with metastatic neuroendocrine tumors.
Intervention: Drug: MK-2206
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 21, 2016)
11
Original Estimated Enrollment  ICMJE
 (submitted: July 22, 2010)
70
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with histologically or cytologically confirmed moderately to well differentiated metastatic or unresectable carcinoid or islet cell tumors.
  • Patient has at least one measurable lesion greater than or equal to 20 mm on CT or MRI imaging.
  • Patients who are on therapy with a somatostatin analog are eligible for entry but must be on a stable dose for at least 3 months with no evidence of tumor shrinkage during that time period.
  • Patient ≥18 years of age on the day of signing informed consent.
  • Patient has performance status 0-1 on the ECOG Performance Scale.
  • Patient has adequate organ function as indicated by the following laboratory values:
  • Absolute Neutrophil Count (ANC)≥1,500/mcL
  • Platelets ≥100,000/mcL
  • Hemoglobin ≥9 g/dL
  • Serum Creatinine ≤2 times the upper limit of normal (ULN)/ OR calculated CrCl ≥60 mL/min (patients with creatinine levels ≥2 times the ULN only). Patient may not be on dialysis
  • Serum total bilirubin ≤1.5 times the ULN
  • AST (SGOT) and ALT (SGPT) ≤5 times the ULN
  • HgbA1c ≤ 8%
  • Fasting Glucose ≤120 mg/dl
  • Creatinine clearance should be calculated by the Cockcroft-Gault method.Fasting is defined as at least 4 hours without oral intake.
  • Patient has voluntarily agreed to participate by giving written informed consent.
  • Previous local therapy (e.g. chemoembolization or bland embolization) is allowed if completed > 6 weeks or 5X half-life prior to study entry. For patients who received local therapy prior to study entry, there must be either documented growth of measurable disease within the embolization field or outside of the embolization field, or both, prior to study entry if the area of the embolization field was the only site of measurable disease.
  • Previous chemotherapy, radiotherapy, and/or biologic therapy, including investigational agents, is/are allowed if completed > 4 weeks prior to study entry (>6 weeks if last regimen contained bevacizumab, BCNU or mitomycin C, and > 6 weeks from last dose of radiation therapy or radiopharmaceutical.
  • Patients must not have disease that is currently amenable to curative surgery. Prior surgery is allowed no less than 6 weeks prior to study entry.
  • Patients with diabetes mellitus are eligible for study entry but must have controlled diabetes as defined by hemoglobin A1c <8.0% within 2 weeks of initiation of protocol therapy.

Exclusion Criteria:

  • Patient has toxicities from prior therapies that have not resolved to grade 1 or grade 0.
  • Patient has known active CNS metastases and/or carcinomatous meningitis are excluded. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids that are used to minimize surrounding brain edema.
  • Patient has an active malignancy of metastatic potential other than the known carcinoid or islet cell tumor, for the past 3 years.
  • Patient has a known hypersensitivity to the components of study drug (MK-2206) or its analogs that is not treatable by premedication with antihistamines and steroids.
  • Patient has a condition, including but not limited to
  • symptomatic congestive heart failure
  • unstable angina pectoris
  • serious 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 is a known diabetic who is poorly controlled (HBAc>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.
  • Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Patient is, at the time of signing informed consent, a regular user (including ―recreational use‖) of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
  • Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
  • Patient is known to be Human Immunodeficiency Virus (HIV)-positive
  • Patient has known history of Hepatitis C or active Hepatitis A or B.
  • Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible.
  • Patient has prior treatment with an mTOR inhibitor such as afinitor, sirolimus, or temsirolimus.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01169649
Other Study ID Numbers  ICMJE 10-067
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Diane Reidy-Lagunes, MD,MS Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP