Dose Escalation Study With MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors (MK-2206-002)

NCT ID: NCT00670488

Last Updated: 2019-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-15
• Study Completion Date: 2011-07-11

Brief Summary

The primary purpose of this study is to investigate the Dose Limiting Toxicities (DLTs), pharmacokinetics (PK), and pharmacodynamics (PD) of MK-2206 administered orally to participants with advanced solid tumors. The preliminary efficacy of MK-2206 will also be investigated.

Conditions

Locally Advanced Tumors; Metastatic Solid Tumors; Cancer; Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MK-2206 30 mg QOD

Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

MK-2206 60 mg QOD

Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

MK-2206 75 mg QOD

Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

MK-2206 90 mg QOD

Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

MK-2206 90 mg QW

Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

MK-2206 135 mg QW

Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

MK-2206 200 mg QW

Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

MK-2206 300 mg QW

Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

MK-2206 250 mg QW

Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

MK-2206 150 mg QW

Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

Interventions

MK-2206

MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant must have confirmed locally advanced or metastatic solid tumors that have failed to respond to standard therapy, have gotten worse or have come back after existing therapy
• Has normal organ function; is no greater than 2 on the ECOG Performance Scale
• Has a negative blood or urine pregnancy test within 72 hours of receiving the first dose of study drug if participant is female
• Is able to swallow capsules and has no surgical or bodily condition that will prevent the patient from swallowing and absorbing oral medications on an ongoing basis

Exclusion Criteria

• Participant has had chemotherapy, radiotherapy, biological therapy or surgery within 4 weeks of starting the study and has not recovered from adverse events caused by the treatment
• Is currently participating or has participated in a study with an investigational compound or device within 30 days
• Has a primary central nervous system tumor
• Has a history or current evidence of heart disease, slow heart rate or untreated high blood pressure
• Is a known diabetic who is taking insulin or oral antidiabetic therapy
• Is pregnant or breastfeeding or planning to become pregnant during the study
• Is HIV-positive
• Has known history of Hepatitis B or C or active Hepatitis A
• Is receiving treatment with oral corticosteroids

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Yap TA, Yan L, Patnaik A, Fearen I, Olmos D, Papadopoulos K, Baird RD, Delgado L, Taylor A, Lupinacci L, Riisnaes R, Pope LL, Heaton SP, Thomas G, Garrett MD, Sullivan DM, de Bono JS, Tolcher AW. First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors. J Clin Oncol. 2011 Dec 10;29(35):4688-95. doi: 10.1200/JCO.2011.35.5263. Epub 2011 Oct 24.

Reference Type: RESULT

PMID: 22025163 (View on PubMed)

Yap TA, Yan L, Patnaik A, Tunariu N, Biondo A, Fearen I, Papadopoulos KP, Olmos D, Baird R, Delgado L, Tetteh E, Beckman RA, Lupinacci L, Riisnaes R, Decordova S, Heaton SP, Swales K, deSouza NM, Leach MO, Garrett MD, Sullivan DM, de Bono JS, Tolcher AW. Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers. Clin Cancer Res. 2014 Nov 15;20(22):5672-85. doi: 10.1158/1078-0432.CCR-14-0868. Epub 2014 Sep 19.

Reference Type: DERIVED

PMID: 25239610 (View on PubMed)

Other Identifiers

2008_513

Identifier Type: OTHER

Identifier Source: secondary_id

MK-2206-002

Identifier Type: OTHER

Identifier Source: secondary_id

2206-002

Identifier Type: -

Identifier Source: org_study_id