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Advanced Malignant Solid NeoplasmPhase 1NCT01480154

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

A Phase 1 study testing Akt Inhibitor MK2206 and Hydroxychloroquine in people with Advanced Malignant Solid Neoplasm and Stage III Cutaneous Melanoma AJCC v7, run by National Cancer Institute (NCI) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Akt Inhibitor MK2206 and Hydroxychloroquine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
1 siteUnited States
Study dates
23 Nov 2011to 31 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Approval for hydroxychloroquine treatment by an eye doctor, based on a screening eye exam; examples of disqualifying baseline conditions may include macular degeneration and other retinal disease such as cataracts that would interfere with required funduscopic examinations, or severe baseline visual impairment, retinopathy or visual field changes; all patients must undergo a screening eye exam prior to enrollment
  • Patients must be able to swallow whole tablets; nasogastric or gastrostomy (G) tube administration is not allowed; tablets must not be crushed or chewed

Who cannot join

  • 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
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  • 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
  • Must not have known hypersensitivity to 4-aminoquinoline compound
  • Must not have retinal or visual field changes from prior 4-aminoquinoline compound use
  • Must not have known glucose-6-phosphate dehydrogenase (G-6PD) deficiency
  • Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
  • Must not be taking hydroxychloroquine for treatment or prophylaxis of malaria
  • Current treatment on another clinical trial; participation in non-therapeutic clinical trials is permissible

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

Other trials in United States

About this study

Official title: A Phase I Trial of MK-2206 and Hydroxychloroquine in Solid Tumors, Melanoma, Renal and Prostate Cancer to Examine the Role of Autophagy in Tumorigenesis

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To define the maximum tolerated dose (MTD) of MK-2206 (Akt inhibitor MK2206) and hydroxychloroquine (HCQ) when used in combination.

SECONDARY OBJECTIVES:

  1. To determine side effects and activity of MK-2206 and hydroxychloroquine when used in combination.

II. To determine if hydroxychloroquine alters the pharmacokinetics of MK-2206 due to a drug-drug interaction.

III. To validate biomarkers for autophagy detection.

OUTLINE: This is a dose-escalation study of Akt inhibitor MK-2206.

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

After completion of study treatment, patients are followed up for 4 weeks.

Being tested
Akt Inhibitor MK2206, Hydroxychloroquine
Medical subject headings
Melanoma, Prostatic Neoplasms, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Akt Inhibitor MK2206Drug

    Also called MK 2206, MK-2206, MK-2206 FREE BASE, MK2206

    Given PO

  • HydroxychloroquineDrug

    Given PO

Study groups in NCT01480154
Study groupRoleWhat they receive
Treatment (Akt inhibitor MK2206, hydroxychloroquine)ExperimentalPatients 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.
Receives: Drug: Akt Inhibitor MK2206; Drug: Hydroxychloroquine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose of Akt inhibitor MK-2206

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

    Measured: 21 days

  2. Dose-limiting toxicity rate

    Will be assessed by CTCAE version 4.0.

    Measured: 21 days

Secondary outcomes (3)

  1. Changes in expression pattern of markers Beclin1, LC3, and p62

    Will be assessed by immunohistochemistry (IHC), Western blotting, and number of autophagosomes by electron microscope (EM). Spaghetti plots or boxplots at time points will be produced for each marker and for EM. Appropriate transformations of the measurements will be carried out to normalize the data. Descriptive summary statistics will be provided for each type of measure at each time point.

    Measured: Baseline to 4 weeks

  2. Change in autophagy activity induced by hydroxychloroquine

    Will be measured by the amount of autophagosomes by EM. Student t-test and Wilcoxon nonparametric tests will be conducted.

    Measured: Baseline to 4 weeks

  3. Validation of Beclin1, LC3, and p62 as markers for autophagy

    Will be measured by EM. Linear mixed models will be fitted to the data, EM as the independent variable, the 3 markers and time points as fixed effects, plus a subject-specific random effect. A backward variable selection will be carried out for the 3 markers until a final model is selected. An ROC curve will be produced. The log-transformed ratio of LC3-II/LC3-I and difference in the log-transformed ratios of LC3-II./LC3-I pre-post treatment between high autophagy activity (HA, >= 6 AV/cell) and low autophagy activity (LA, < 6 AV/cell) will be analyzed for evaluating treatment effect using a two sided paired t-test.

    Measured: Up to 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Nov 2011 (estimated)
  2. Study start23 Nov 2011
  3. Primary completion14 Feb 2020
  4. Study completion31 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01480154
Sponsor's protocol ID
NCI-2012-00084
Other IDs
NCI-2012-00084, 051105, CDR0000717546, CINJ-051105, 8983, 8983, P30CA072720, U01CA132194
Status last verified
Sep 2026
First submitted
23 Nov 2011
Last updated
9 Sep 2026
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Akt Inhibitor MK2206 and Hydroxychloroquine in people with Advanced Malignant Solid Neoplasm and Stage III Cutaneous Melanoma AJCC v7, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose of Akt inhibitor MK-2206 (time frame: 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01480154.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.

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