Clinical trial · Interventional

A Phase I Study of MK-2206 in Combination With Standard Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (MK-2206-003)

A Phase I Dose Escalation Study of MK-2206 in Combination With Standard Doses of Selected Chemotherapies or Targeted Agents in Patients With Locally Advanced or Metastatic Solid Tumors

NCT00848718CI-TRIAL-00041558completedPhase 1Results postedClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

The purpose of this study is to compare the safety and tolerability of several dose levels of MK-2206 in combination with chemotherapy and targeted therapy agents in participants with locally advanced or metastatic solid tumors. The primary hypotheses are that administration of MK-2206 in combination with either carboplatin + paclitaxel, docetaxel, or erlotinib in participants with locally advanced or metastatic solid tumors will have acceptable tolerability, a dose limiting toxicity (DLT) rate of ≤30%, plasma exposure and pharmacodynamics that exceed target thresholds, and allow for definition of a maximum tolerated dose (MTD) in each of the 3 combinations.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Locally Advanced, Metastatic Solid Tumors	—	UNRESOLVED	—

Interventions

Interventions (6)

Intervention	Type	Mapped drug	Match
carboplatin	Drug	Carboplatin	ALIAS
corticosteroid	Drug	—	UNRESOLVED
docetaxel	Drug	Docetaxel	ALIAS
erlotinib	Drug	Erlotinib	ALIAS
MK-2206	Drug	Akt Inhibitor MK2206	ALIAS
paclitaxel	Drug	Paclitaxel	ALIAS

Design

Arms and outcomes

Arms (3)

type
EXPERIMENTAL
label
MK-2206 + carboplatin + paclitaxel
description
MK-2206 combined with carboplatin and paclitaxel
interventionNames
1. Drug: MK-2206
2. Drug: carboplatin
3. Drug: paclitaxel
type
EXPERIMENTAL
label
MK-2206 + docetaxel
description
MK-2206 combined with docetaxel plus pretreatment with a corticosteroid
interventionNames
1. Drug: MK-2206
2. Drug: docetaxel
3. Drug: corticosteroid
type
EXPERIMENTAL
label
MK-2206 + erlotinib

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

Inclusion Criteria :

* Participants must have locally advanced or metastatic solid tumors.
* Participant is male or female greater than or equal to 18 years of age.
* Participant must have a performance status less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
* Female participants of childbearing potential has a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication.
* Participants in the MK-2206 + carboplatin/paclitaxel and MK-2206 + docetaxel treatment arms will be limited to no more than 3 prior cytotoxic therapies for metastatic or recurrent diseases.
* Participant is able to swallow capsules and has no surgical or anatomical condition that will prevent the Participant from swallowing.

Exclusion Criteria:

* Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks.
* Participants must be least 4 weeks post-surgery and do not expect major surgery in the study duration.
* Participant is currently participating or has participated in a study with an investigational compound or device within 30 days.
* Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Participant with a primary central nervous system tumor.
* Participant has known hypersensitivity to the components of study drug.
* Participant has a history or current evidence of heart disease.
* Participant has evidence of clinically significant bradycardia (slow heart rate).
* Participant has uncontrolled high blood pressure.
* Participant at significant risk for hypokalemia (low potassium levels).
* Participant is a known diabetic
* Participant has known psychiatric or substance abuse disorders.
* Participant is a user of illicit drugs.
* Participant is pregnant or breastfeeding.
* Participant is Human Immunodeficiency Virus (HIV) positive.
* Participant has known history of Hepatitis B or C or active Hepatitis A.
* Participant has symptomatic ascites or pleural effusion.
* Participant is receiving treatment with oral corticosteroids.
* Participant is using a potent cytochrome P(450) 3A4 (CYP3A4) inhibitor or inducer.

References

Publications (1)

DERIVEDMolife LR, Yan L, Vitfell-Rasmussen J, Zernhelt AM, Sullivan DM, Cassier PA, Chen E, Biondo A, Tetteh E, Siu LL, Patnaik A, Papadopoulos KP, de Bono JS, Tolcher AW, Minton S. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. J Hematol Oncol. 2014 Jan 3;7:1. doi: 10.1186/1756-8722-7-1. PMID 24387695