MK2206 + Hydroxychloroquine for Advanced Cancers

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: QTc prolonging drugs, Insulin, Antiretrovirals, CYP3A4 modulators

Disqualifiers: Uncontrolled diabetes, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days per cycle

62 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot be on certain medications that affect the heart's rhythm or those that interact with the trial drugs. If you're on medications that affect the liver enzyme CYP3A4, the trial team will review your case to see if you can switch to other medications.

What evidence supports the effectiveness of the drug combination MK2206 and Hydroxychloroquine for advanced cancers?

Research shows that combining Hydroxychloroquine with Akt inhibitors like MK2206 can make cancer treatments more effective by specifically targeting cancer cells and enhancing their destruction, while having minimal effects on normal cells. ^{1 2 3 4 5}

What makes the drug MK2206 + Hydroxychloroquine unique for treating advanced cancers?

The combination of MK2206, an Akt inhibitor, and Hydroxychloroquine, which is traditionally used for malaria and autoimmune diseases, is unique because it targets cancer cells by inhibiting a specific pathway (Akt pathway) that is often overactive in cancer, while Hydroxychloroquine may enhance the effect by disrupting cancer cell survival mechanisms. ^{6 7 8 9 10}

What is the purpose of this trial?

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.

Research Team

Jyoti Malhotra, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

This trial is for adults with advanced solid tumors, melanoma, prostate or kidney cancer who have tried at least one standard treatment. They must be able to swallow tablets, not be pregnant or breastfeeding, and agree to use contraception. People with certain eye diseases, uncontrolled diabetes, active infections or heart problems can't join.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

I have recovered from any side effects of my previous cancer treatments.

My kidney function is within the required range for the trial.

Exclusion Criteria

I can swallow and retain medication without issues.

I am not pregnant or nursing.

I am HIV-positive and not on antiretroviral therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Akt inhibitor MK2206
• Hydroxychloroquine

Trial Overview The trial tests the combination of Akt Inhibitor MK2206 and Hydroxychloroquine on tumor growth. MK2206 blocks enzymes needed for cell growth while Hydroxychloroquine aims to kill or stop tumor cells from dividing and spreading.

Participant Groups

Group I: Treatment (Akt inhibitor MK2206, hydroxychloroquine) Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

A phase 2b trial showed that adding sorafenib to capecitabine significantly improved progression-free survival in patients with HER2-negative advanced breast cancer, with a median PFS of 6.4 months compared to 4.1 months for placebo.

The ongoing phase 3 RESILIENCE trial aims to confirm these findings with a target enrollment of approximately 519 patients, focusing on the safety and efficacy of the sorafenib and capecitabine combination, while implementing a dosing strategy to manage potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 tRial comparing capecitabinE in combination with SorafenIb or pLacebo for treatment of locally advanced or metastatIc HER2-Negative breast CancEr (the RESILIENCE study): study protocol for a randomized controlled trial. Baselga, J., Costa, F., Gomez, H., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of MK-2206 and hydroxychloroquine in patients with advanced solid tumors. [2021]

2. France pubmed.ncbi.nlm.nih.gov

A 4-aminoquinoline derivative that markedly sensitizes tumor cell killing by Akt inhibitors with a minimum cytotoxicity to non-cancer cells. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

MK-2206 and Standard Neoadjuvant Chemotherapy Improves Response in Patients With Human Epidermal Growth Factor Receptor 2-Positive and/or Hormone Receptor-Negative Breast Cancers in the I-SPY 2 Trial. [2021]

4. England pubmed.ncbi.nlm.nih.gov

The efficacy and selectivity of tumor cell killing by Akt inhibitors are substantially increased by chloroquine. [2013]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

New use for old drugs? Prospective targets of chloroquines in cancer therapy. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A phase 3 tRial comparing capecitabinE in combination with SorafenIb or pLacebo for treatment of locally advanced or metastatIc HER2-Negative breast CancEr (the RESILIENCE study): study protocol for a randomized controlled trial. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Folate receptor-targeted lipid-albumin nanoparticles (F-LAN) for therapeutic delivery of an Akt1 antisense oligonucleotide. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Results from a biomarker study to accompany a phase II trial of RRx-001 with reintroduced platinum-based chemotherapy in relapsed small cell carcinoma. [2022]