Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

NCT01480154 | Active Not Recruiting Phase 1

• 8 other identifiers: NCI-2012-00084051105CDR0000717546CINJ-0511058983P30CA072720U01CA132194UM1CA186716
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and the best dose of Akt inhibitor MK2206 together with hydroxychloroquine in treating patients with advanced solid tumors, melanoma, prostate or kidney cancer. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Akt inhibitor MK2206 together with hydroxychloroquine may kill more tumor cells than giving either drug alone.

Conditions

Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage III Prostate Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Stage III Cutaneous Melanoma AJCC v7; Advanced Malignant Solid Neoplasm; Stage IIIC Cutaneous Melanoma AJCC v7

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of Akt inhibitor MK-2206

  Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  21 days

• Dose-limiting toxicity rate

  Will be assessed by CTCAE version 4.0.

  21 days

Secondary Outcomes (3)

• Changes in expression pattern of markers Beclin1, LC3, and p62

  Baseline to 4 weeks

• Change in autophagy activity induced by hydroxychloroquine

  Baseline to 4 weeks

• Validation of Beclin1, LC3, and p62 as markers for autophagy

  Up to 4 weeks

Study Arms (1)

Treatment (Akt inhibitor MK2206, hydroxychloroquine)

EXPERIMENTAL

Patients receive Akt inhibitor MK2206 PO on days 1, 8, and 15. Beginning on cycle 2, patients also receive hydroxychloroquine PO BID on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Akt Inhibitor MK2206; Drug: Hydroxychloroquine

Interventions

Hydroxychloroquine DRUG

Given PO

Treatment (Akt inhibitor MK2206, hydroxychloroquine)

Akt Inhibitor MK2206 DRUG

Given PO

Also known as: MK 2206, MK-2206, MK-2206 FREE BASE, MK2206

Treatment (Akt inhibitor MK2206, hydroxychloroquine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically proven advanced solid cancer and have undergone treatment with at least one regimen of standard therapy, either cytotoxic chemotherapy, a molecularly targeted agent, or immunotherapy, or have a form of cancer for which no standard therapy exists; patients with prostate cancer may continue on androgen-deprivation therapy if they are currently receiving it
• Patient must have recovered from toxicity of prior chemotherapy, molecularly targeted agents and/or radiotherapy; patient may not have received chemotherapy in the prior 4 weeks (6 weeks for nitrosoureas or mitomycin C); patients may have not received a molecularly targeted agent within the past 4 weeks or 5 half lives (whichever is less); patients may not have received radiotherapy in the prior 3 weeks
• Patients must be willing and able to sign informed consent
• Leukocytes \>= 3,000/mcL (obtained within 7 days of treatment initiation)
• Absolute neutrophil count \>= 1,500/mcL (obtained within 7 days of treatment initiation)
• Platelets \>= 100,000/mcL (obtained within 7 days of treatment initiation)
• Total serum bilirubin within normal institutional limits (obtained within 7 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal (obtained within 7 days of treatment initiation)
• Creatinine =\< grade 1 OR creatinine clearance \>= 40 mL/min/1.73 m\^2 for patients with creatinine (Cr) above normal institutional limits; a calculated creatinine clearance by Cockcroft-Gault Formula is acceptable in lieu of a measured value (obtained within 7 days of treatment initiation)
• All patients must have measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Estimated life expectancy of at least 12 weeks
• Women must: have a negative serum or urine pregnancy test within 7 days prior to study entry if she is a woman of child-bearing potential (WOCBP), or be at least one year post-menopausal, OR be surgically sterile
• The effects of MK-2206 on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for 6 months after study participation; acceptable methods of contraception include hormonal, barrier methods, intrauterine device, tubal ligation/vasectomy or abstinence; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; acceptable methods of contraception include hormonal, barrier methods, intrauterine device, tubal ligation/vasectomy or abstinence; women should not breast feed while on treatment with MK-2206 and hydroxychloroquine
• Patients must not have a history of any condition (social or medical) that, in the opinion of the investigator, might interfere with the patient's ability to comply with the protocol or pose additional or unacceptable risk to the patient

You may not qualify if:

• Failure to recover fully (as judged by the investigator) from prior surgical procedures, or failure to recover from adverse events (grade =\< 1) due to agents administered more than 4 weeks earlier
• Concurrent treatment with an investigational agent other than the investigational agent(s) used in this study OR treatment within 4 weeks of study entry with any investigational agent(s) or device(s)
• Patients with corrected QT interval (QTc) prolongation greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 (\> 480 msec); in addition, patients should not be receiving non-study medications known to prolong QTc
• Patients on treatment for rheumatoid arthritis or systemic lupus erythematosus
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study
• Patient has uncontrolled diabetes, defined as a fasting serum glucose \> 150 mg/dl or glycosylated hemoglobin (hemoglobin A1c \[HbA1c\]) \> 7% at screening
• Diabetic patients requiring insulin for glucose control at the time of study entry
• Patient must not have ongoing ventricular cardiac dysrhythmias of grade \>= 2 as described by the Cancer Therapy Evaluation Program (CTEP) version 4.0 of the National Cancer Institute (NCI) CTCAE
• Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous \[IV\] alimentation, prior surgical procedures affecting absorption, ulcerative colitis, inflammatory bowel disease, a partial or complete small bowel obstruction, or active peptic ulcer disease) that impairs their ability to swallow and retain MK-2206 or hydroxychloroquine tablets
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would affect safety or limit compliance with study requirements
• Pregnant and nursing women are excluded from this study because developmental and reproductive toxicity studies of MK-2206 have not been performed
• Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MK-2206 or HCQ used in this study
• Because MK-2206 is metabolized primarily by the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) liver enzyme, the eligibility of patients taking medications that are potent inducers or inhibitors of that enzyme will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications
• Patients with active central nervous system (CNS) metastases are excluded; patients with CNS metastases that have been treated must be off steroid treatment for \> 2 months and be asymptomatic; patients that have symptoms to suggest CNS metastases should have a brain magnetic resonance imaging (MRI) within 28 days of enrollment to confirm the absence of CNS metastases; contrast computed tomography (CT) is acceptable for patients who are unable to undergo a brain MRI
• Must not have psoriasis or porphyria

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Conditions

Melanoma; Prostatic Neoplasms; Carcinoma, Renal Cell

Interventions

MK 2206; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Kidney Diseases; Urologic Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jyoti Malhotra

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2011
• First Posted: November 28, 2011
• Study Start: November 23, 2011
• Primary Completion: February 14, 2020
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

US (1)