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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs for treating advanced cancers such as melanoma, prostate, or kidney cancer. The goal is to determine the optimal dosage and assess how these drugs work together to halt cancer growth. Specifically, the trial combines an Akt inhibitor (MK2206), which blocks enzymes that promote tumor cell growth, with hydroxychloroquine, a chemotherapy drug that kills or prevents the spread of cancer cells. Suitable candidates for this trial have previously undergone other cancer treatments and have advanced solid tumors. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the drug MK2206 has been tested in people with advanced cancers. These studies found that MK2206 is generally safe, though some individuals experienced side effects such as skin rashes and diarrhea. Most participants managed these side effects well.

Hydroxychloroquine is often used alongside other cancer treatments. It has shown promise in fighting cancer by blocking a process that cancer cells use to survive. Some studies have found that long-term use can cause side effects, usually related to the dose. However, short-term use with other drugs has been better tolerated, with fewer side effects.

Overall, these treatments have been tested and are considered safe for clinical trials. It is important to be aware of possible side effects and discuss any concerns with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining the Akt inhibitor MK2206 with hydroxychloroquine for advanced cancers because it targets cancer cells differently from standard treatments. Most current therapies focus on traditional chemotherapy or targeted therapies that inhibit specific proteins. However, MK2206 disrupts the Akt signaling pathway, which is crucial for cancer cell survival and growth. Adding hydroxychloroquine may enhance this effect by interfering with the cancer cells' ability to recycle components, potentially making them more vulnerable to treatment. This combination approach could offer hope for patients with advanced cancers who have limited options.

What evidence suggests that this treatment might be an effective treatment for advanced cancers?

Research has shown that the drug MK2206, which participants in this trial will receive, can help fight cancer by blocking certain proteins that allow tumor cells to grow. It has increased the death of cancer cells and stopped their growth, especially in breast cancer. In this trial, participants will also receive hydroxychloroquine starting in cycle 2. Studies suggest that hydroxychloroquine can be effective in cancer treatment by preventing cancer cells from recycling waste, which they need to survive. It also helps kill cancer cells and stop them from spreading. When used together, these drugs may work better than when used alone, providing a stronger attack on cancer cells. ^{2 3 6 7 8}

Who Is on the Research Team?

Jyoti Malhotra, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3772348/

Biomarkers of Response to Akt Inhibitor MK-2206 in Breast ...

MK-2206 inhibited Akt signaling and cell-cycle progression, and increased apoptosis in a dose-dependent manner in breast cancer cell lines.

2.

aacrjournals.org

aacrjournals.org/mct/article/9/7/1956/93857/MK-2206-an-Allosteric-Akt-Inhibitor-Enhances

MK-2206, an Allosteric Akt Inhibitor, Enhances Antitumor ...

These results suggest that MK-2206 may significantly enhance the antitumor efficacy of docetaxel against breast tumors when administered in a stepwise schedule.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01277757

Akt Inhibitor MK2206 in Treating Patients With Advanced ...

This phase II trial studies how well Akt inhibitor MK2206 works in treating patients with breast cancer cancer that has spread to other places in the body ...

4.

breast-cancer-research.biomedcentral.com

breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-019-1154-8

Phase II trial of AKT inhibitor MK-2206 in patients with ...

We conducted a phase II trial with an allosteric AKT inhibitor MK-2206 in patients with advanced breast cancer who had tumors with PIK3CA/AKT1 mutations and/or ...

5.

nature.com

nature.com/articles/srep12122

Results of an abbreviated phase-II study with the Akt ...

The clinical efficacy of Akt inhibition in advanced biliary cancers with pAkt overexpression may merit furhter investigation in future studies.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4233149/

Interrogating two schedules of the AKT inhibitor MK-2206 in ...

Patients with advanced cancers were enrolled onto a QW dose-escalation phase I study to investigate the safety and pharmacokinetic-pharmacodynamic profiles of ...

7.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(19)64393-0/fulltext

Safety and Efficacy of MK-8669 (Ridaforolimus) + MK-2206 ...

Ridaforolimus and MK-2206 show activity in heavily pre-treated hormone positive and negative breast cancer patients exhibiting PI3K pathway dependence.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7106976/

MK-2206 and Standard Neoadjuvant Chemotherapy ...

Preclinical studies have suggested that PI3K and Akt inhibitors enhance the efficacy of antimicrotubule drugs in human breast cancer cells. Safety and clinical ...