Return to List

Study Summary
No. 2009-0878:.......Colorectum; Melanoma; Pancreas; Solid Tumors......Chris Garrett......Gastrointestinal Medical Oncology
.
Study Summary Title
Study Summary
Number:
2009-0878
Study Title:A Phase I Study of Oral MK-2206 in Combination with Oral AZD6244 in Patients with Locally Advanced or Metastatic Solid Tumors (010-03)
.
Physician New Patient Referral
Name:Chris GarrettPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Gastrointestinal Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2828
Contact us about clinical trials
.
General Information
Disease Group:Colorectum
Melanoma
Pancreas
Solid Tumors
Supported By:Merck & Co., Inc.
Phase of Study:Phase IReturn
Visit:
Return visit schedule varies depending upon the cycle. Cycle 1 may require up
to 13 study visits, depending upon assigned MK-2206 dosing schedule. Cycle 2
requires 4 study visits, and subsequent cycles require 1 study visit per cycle.
Treatment
Agents:
AZD6244
MK-2206
Home Care:Both study drugs are oral so participants may self administer the drugs at
home.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
Not applicable.
Description/
Intervention:
The goal of the first part (Part A) of this clinical research study is to find
the highest tolerated dose and best treatment schedule of the combination of
MK-2206 and AZD6244 that can be given safely to patients with advanced cancer.

The goal of the second part (Part B) is to further test the highest tolerated
dose of MK-2206 and AZD6244 when given to patients with cancer of the pancreas,
colon, rectum, or melanoma (a type of skin cancer).
.
Study Objectives / Outcomes
Primary
(1) To define the dose-limiting toxicity (DLT) and identify a maximum tolerated dose (MTD) of combination therapy with MK-2206 and AZD6244 in adult patients with locally advanced or metastatic solid tumors.
(2) To characterize the safety and tolerability of combination therapy with MK-2206 and AZD6244 administered orally to adult patients with locally advanced or metastatic solid tumors.

Secondary
(1) To preliminarily evaluate the anti-tumor activity of combination therapy with MK-2206 and AZD6244 in solid tumors using Response Evaluation Criteria in Solid Tumors (RECIST).
(2) To determine the recommended Phase II dose (RP2D) of combination therapy with MK-2206 and AZD6244.

Exploratory
(1) To correlate genetic activating mutation events in the phosphatidylinositol-3-kinase (PI3K) and RAS/RAF pathways to responses following combination treatment of MK-2206 and AZD6244.
(2) At selected time points, to measure plasma concentrations of MK-2206 and AZD6244 when administered in combination.
(3) To assess target and pathway inhibition of combination therapy with MK-2206 and AZD6244 in blood and tumor tissue.
.
Study Status Information
Study Activation / Registration Date:06/28/2010
IRB Review and Approval Date:06/28/2010
Study Type:Phase I
Recruitment Status:Open
Projected Accrual:105
.
Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patient must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy or therapies known to provide clinical benefit, or for whom efficacious standard therapy or any other therapy known to provide clinical benefit does not exist.

2) Patient is male or female, and >/= 18 years of age on day of signing informed consent.

3) Patient must have performance status of 0 or 1 on the ECOG Performance Scale.

4) Patient must have adequate organ function as indicated by the following laboratory values: absolute neutrophil count >/= 1,500/mcL; platelets >/= 100,000/mcL; hemoglobin >/= 9 g/dL without transfusion or erythropoietin (EPO) dependency; serum creatinine </= 1.5 times (X) upper limit of normal (ULN) or calculated/measured creatinine clearance >/= 60 mL/minute for patients with creatinine levels > 1.5 X institutional ULN;

5) (Continued) Serum total bilirubin in normal range; direct bilirubin in normal range; for patients with Gilbert's syndrome, total bilirubin may be > 1.5 X ULN, however direct bilirubin must be normal; AST (SGOT) and ALT (SGPT) </= 2.5 X ULN; alkaline phosphatase </= 2.5 X ULN; prothrombin time (PT) </= 1.2 X ULN; partial thromboplastin time (PTT) </= 1.2 X ULN.

6) Women enrolled in the study, who are not free from menses for >1 year, post hysterectomy / oophorectomy, or surgically sterilized, are willing to use 2 adequate barrier methods of contraception to prevent pregnancy or to abstain from heterosexual activity throughout the study, starting with Visit 1 through 30 days after the last dose of study drug. Approved contraceptive methods include for example, intra-uterine device, diaphragm with spermicide, cervical cap with spermicide, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception.

7) Male patient agrees to use an adequate method of contraception starting with the first dose of study drug through 16 weeks after the last dose of study drugs.

8) Patient has voluntarily agreed to participate by giving written informed consent.

9) Patient has no history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma with Prostate Specific Antigen (PSA) <1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician.

10) Patient has at least one assessable (measurable or non-measurable) lesion as defined by RECIST.

11) Patient is able to swallow oral medications and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis

12) For the second half of Part A and for Part B, patients must have melanoma, colorectal cancer (CRC) or pancreatic cancer (This criterion is waived for the initial 3-6 patients enrolled at each dose level in Part A and is mandatory for the subsequent 6-9 patients enrolled at each dose level in Part A as well as Part B of the study. NOTE: If response is seen in any given tumor type during dose escalation, the MTD expansion may also include patients with this tumor type)

13) In Part B, patients with melanoma must be willing to undergo pre-dose and post-dose biopsies (This criterion is waived during Part A and mandatory for Part B).

14) In Part B, if approximately >/= 50% of the patients enrolled in the study demonstrate wild-type KRAS or BRAF mutation status, subsequent enrollment to the study will require demonstration of either KRAS or BRAF mutation status prior to study entry. Mutations detected in either tumor or blood samples are acceptable for satisfying this criterion. (This criterion is waived during initial enrollment in the study, however may be mandated during enrollment of Part B of the study at discretion of the SPONSOR and after discussion with the Investigator).

Exclusion Criteria:1) Patient who has had chemotherapy, radiotherapy with wide field radiation, or biological therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C), prior to entering the study or who has not recovered from adverse events due to agents administered more than 4 weeks prior to Study Cycle 1 Day 1. If the patient has residual toxicity from prior treatment, toxicity must be </= Grade 1. Radiotherapy with a limited field of radiation within 2 weeks of the first dose of treatment is permitted for palliative purposes.

2) Patient is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5 times the half-life, from prior agents, whichever is longer, of Study Cycle 1 Day 1.

3) Patients with known central nervous system (CNS) metastases and/or carcinomatous meningitis are excluded. However, patients with CNS metastases who have completed a course of therapy are eligible for the study provided they are asymptomatic for 3 months prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids and anti-epileptic therapy.

4) Patient with a known primary central nervous system tumor or spinal cord compression.

5) Patient has known hypersensitivity to the components of study drug(s) or its analogs.

6) Patient has a previous or current condition, therapy, or laboratory abnormality that may confound the results of the study, interfere with the patient's participation for the full duration of the study, or increase the risk to the patient such that participation is not in his/her best interest, at the discretion of the investigator.

7) Patient has known psychiatric or substance abuse disorders that would interfere with compliance with study requirements.

8) 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.

9) Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.

10) Patient is known to be Human Immunodeficiency Virus (HIV)-positive.

11) Patient has a known history of Hepatitis B or C, or active hepatitis A.

12) Patient has symptomatic (>/= Grade 2) ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible.

13) Patients must be at least 4 weeks post major surgery.

14) Patient has a history or current evidence of heart disease including: a) congestive heart failure New York Heart Association (NYHA) class 2 or greater, b) unstable angina pectoris, c) cardiac arrhythmia including atrial fibrillation with atrial rate > 100 beats per minute, d) history or current evidence of a myocardial infarction during the last 6 months, and/or a current electrocardiogram (ECG) tracing that is abnormal in the opinion of the treating Investigator, e) QTc prolongation >450 millisecond (msec) (Bazett's Formula)

15) (Continued from # 13) f) congenitally long QT syndrome, and/or current anti-arrhythmic therapy, has received any marketed or experimental compound in the last 4 weeks prior to entering the study with possible or known effects of QT prolongation, or cumulative high-dose anthracycline therapy, g) Left ventricular ejection fraction </= 50%.

16) Patient with evidence of clinically significant bradycardia (heart rate <50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree atrioventricular (AV) block (Mobitz Type 2), or patients taking beta blockers, non-dihydropyridine calcium channel blockers, or digoxin.

17) Patient with uncontrolled hypertension [i.e., >/= 150/95 millimeters of mercury (mHg) sitting blood pressure (SiBP)]. Patients who are controlled on antihypertensive medication will be allowed to enter the study.

18) Patient at significant risk for hypokalemia (e.g., patients on high dose diuretics, or with recurrent diarrhea)

19) Patient with poorly controlled diabetic conditions [glycated hemoglobin (HBA1C) >8%]

20) Patient with refractory nausea and/or vomiting, chronic gastrointestinal disease (e.g.inflammatory bowel disease) or significant bowel resection of other condition which in the condition of the investigator could interfere with absorption of study medication.

.
Links
Registration Number: NCT01021748
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
.
Results


Return to Clinical Trials at M.D. Anderson Cancer Center