Clinical trial NCT01021748: A Combination Therapy Study of MK-2206 and AZD6244 in Participants With Advanced Solid Tumors (MK-2206-010)
Official title: A Phase I Study of Oral MK-2206 in Combination With Oral AZD6244 in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced or Metastatic Solid Tumors
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2009-11-30
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will investigate the safety and tolerability of combination therapy with MK-2206 and AZD6244 (selumetinib) and determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) for this drug combination in the treatment of participants with locally advanced or metastatic solid tumors. Preliminary efficacy data will also be collected.

The primary hypotheses for this study are that: 1) the Dose-limiting Toxicities (DLTs) observed in participants with locally advanced or metastatic solid tumors after administration of combination therapy with MK-2206 and AZD6244 will be dose-dependent and allow for identification of the MTD, and 2) oral administration of combination therapy with MK-2206 and AZD6244 to participants with advanced solid tumors will be generally well-tolerated.


Eligibility criteria: Inclusion Criteria:

* Participant has 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
* Participant has no history of prior cancer, except certain cervical, skin, or prostate cancers, or has undergone potentially curative therapy with no evidence of disease for 5 years
* At least 18 years of age
* Participant is able to swallow oral medications
* For participants enrolled in the MTD expansion cohorts, must have a diagnosis of Kirsten rat sarcoma viral oncogene homolog (KRAS) tumor-type non small-cell lung cancer (NSCLC). Additional tumor types (with specific mutations) may be added to the MTD expansion cohorts after discussion between Sponsor and Investigator

Exclusion Criteria:

* Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks of entering the study
* Participant is currently participating in or has participated in a study of an investigational compound or device within 30 days or 5x the compound's half-life of Cycle 1, Day 1
* Participant has known central nervous system metastases and/or carcinomatous meningitis
* Participant has a primary central nervous system tumor or spinal cord compression
* Participant 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
* Participant is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study
* Participant is human immunodeficiency virus (HIV) positive
* Participant is has history of hepatitis B or C or active hepatitis A
* Participant has a history or current evidence of heart disease
* Participant has uncontrolled high blood pressure
* Participant has poorly controlled diabetes

Primary outcomes:
measure: Number of Participants With a Dose-limiting Toxicity (DLT)
timeFrame: Cycle 1 (Up to 28 days)
measure: Number of Participants Who Experienced at Least One Adverse Event (AE)
timeFrame: Up to approximately 23 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 20 months
Secondary outcomes:
measure: Number of Participants With a Tumor Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Baseline and after every 8 weeks of treatment until documentation of objective response or disease progression (Up to 2 years)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Tolcher AW, Khan K, Ong M, Banerji U, Papadimitrakopoulou V, Gandara DR, Patnaik A, Baird RD, Olmos D, Garrett CR, Skolnik JM, Rubin EH, Smith PD, Huang P, Learoyd M, Shannon KA, Morosky A, Tetteh E, Jou YM, Papadopoulos KP, Moreno V, Kaiser B, Yap TA, Yan L, de Bono JS. Antitumor activity in RAS-driven tumors by blocking AKT and MEK. Clin Cancer Res. 2015 Feb 15;21(4):739-48. doi: 10.1158/1078-0432.CCR-14-1901. Epub 2014 Dec 16.