Hydroxychloroquine + Everolimus for Breast Cancer

Overseen By Angela DeMichele, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center at Penn Medicine

Must be taking: Lipid lowering

Must not be taking: mTOR inhibitors, Corticosteroids

Disqualifiers: Heart failure, Diabetes, Hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether hydroxychloroquine (HCQ), a medication often used to prevent and treat malaria, and everolimus (EVE), an mTOR inhibitor, can help prevent breast cancer recurrence in patients who have completed their main treatments. Researchers are examining three groups: one receiving only HCQ, another only EVE, and a third receiving both treatments together. The trial targets individuals diagnosed with invasive breast cancer within the last 5 years, who have completed all primary treatments, and have specific cancer cells in their bone marrow. This trial may suit those who have undergone surgery and chemotherapy and meet these specific conditions. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you can continue taking adjuvant endocrine and bone-modifying agents as per standard care guidelines. If you are on anticoagulants, they must be managed around certain procedures.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that hydroxychloroquine (HCQ) is generally safe and well-tolerated. One study found that patients could take doses up to 800 mg per day without major issues, suggesting HCQ might also be safe for cancer treatment.

For everolimus, several studies have demonstrated its safety. In one trial, patients with advanced breast cancer tolerated everolimus well when combined with another drug. While some side effects occurred, they were similar to those observed in other studies.

The combination of HCQ and everolimus is still under investigation. A recent study is testing the safety of this combination for breast cancer patients. Based on earlier research with each drug alone, there is hope that the combination might also be safe. However, further research is needed to confirm this.

Overall, both HCQ and everolimus have demonstrated safety for patients, but the safety of their combined use remains under study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Hydroxychloroquine and Everolimus for breast cancer because it targets the disease in a novel way. Hydroxychloroquine is known for its potential to block autophagy, a process cancer cells use to survive, while Everolimus is an mTOR inhibitor that disrupts cancer cell growth and proliferation. Unlike standard treatments like hormone therapies or chemotherapy, this combination aims to starve cancer cells and prevent their growth simultaneously. This dual mechanism offers a promising new approach that could enhance treatment effectiveness and potentially overcome resistance seen with traditional therapies.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will evaluate Hydroxychloroquine (HCQ) and Everolimus (EVE) as separate and combined treatments for breast cancer. Studies have shown that HCQ can combat breast cancer by halting autophagy, a process where cancer cells clean up and reuse parts of themselves to survive. In lab tests, HCQ has enhanced the effectiveness of treatments that block estrogen in cancer cells. Research has also shown that adding Everolimus to hormone therapy can significantly delay the recurrence of breast cancer. Evidence suggests that using HCQ and Everolimus together could inhibit cancer cell growth by blocking essential enzymes. In a recent study, this combination treatment resulted in a 100% rate of no cancer recurrence during the study period. Participants in this trial may receive HCQ alone, EVE alone, or the combination of HCQ and EVE. ^{2 6 7 8 9}

Who Is on the Research Team?

Angela DeMichele, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've finished primary breast cancer therapy, have no signs of recurrence, and show bone marrow tumor cells. They must be healthy enough with good organ function and not pregnant or on other trials. Prior mTOR inhibitor treatment or hypersensitivity to Everolimus disqualifies them.

Inclusion Criteria

I don't have health issues that prevent me from taking study drugs.

Tests show that there are cancer cells in the bone marrow after treatment.

I am currently taking hormone therapy and bone-strengthening medications as part of my treatment.

Exclusion Criteria

Concurrent enrollment on another investigational therapy

I have not received any live vaccines within a week before or during the study.

I am not pregnant, breastfeeding, and I use effective birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HCQ, EVE, or the combination for 6 cycles

6 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Everolimus
• Hydroxychloroquine

Trial Overview The CLEVER Pilot Trial tests Hydroxychloroquine (HCQ), Everolimus (EVE), or their combination in preventing recurrent breast cancer in patients with residual disease indicators after primary therapy.

How Is the Trial Designed?

Group I: combination HCQ and EVE (Arm C+D) Experimental Treatment 2 Interventions

Group II: HCQ alone (Arm A) Experimental Treatment 1 Intervention

Group III: EVE alone (Arm B) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Published Research Related to This Trial

The EVA study, involving 404 patients with HR+ advanced breast cancer, demonstrated that the combination of Everolimus (EVE) and Exemestane (EXE) is safe, with an overall response rate (ORR) of 31.6% and a disease control rate (DCR) of 60.7%.

Patients who received the full dose of EVE or had prior treatment with Fulvestrant showed better treatment responses, highlighting the importance of dose intensity and previous therapies in optimizing outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Everolimus and Exemestane in hormone-receptor positive (HR+) human-epidermal-growth-factor negative (HER2-) advanced breast cancer patients: New insights beyond clinical trials. The EVA study. Cazzaniga, ME., Airoldi, M., Arcangeli, V., et al.[2018]

A review of seven targeted cancer therapies (sunitinib, pazopanib, bevacizumab, temsirolimus, axitinib, everolimus, and sorafenib) revealed that all these medications are associated with adverse events, highlighting the importance of monitoring patients closely.

Effective management strategies for these side effects can prevent them from becoming severe, which is crucial to maintaining the full efficacy of the treatments and avoiding unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma. Alasker, A., Meskawi, M., Sun, M., et al.[2022]

In the BALLET trial involving 2131 postmenopausal patients with hormone-receptor positive HER2-negative breast cancer, the combination of everolimus and exemestane significantly improved progression-free survival while maintaining a manageable safety profile.

The most common adverse events, such as stomatitis and asthenia, typically occurred within the first three months of treatment, highlighting the importance of close monitoring and early intervention during this period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus plus exemestane in hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: incidence and time course of adverse events in the phase IIIb BALLET population. Ciruelos, E., Jerusalem, G., Martin, M., et al.[2021]

Everolimus, an oral mTOR inhibitor, significantly improves progression-free survival in patients with clear cell renal cancer, increasing it from a median of 1.9 months to 4.9 months in a phase III trial with a hazard ratio of 0.33 (P < 0.001).

The treatment is generally well-tolerated, with mild to moderate side effects that can be managed, and it has been approved as a validated option for patients who have progressed on VEGFR inhibitors, with ongoing trials exploring its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and/or sorafenib. Coppin, C.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9954606/

Long-Term Results with Everolimus in Advanced Hormone ... Using statistical methods fit for real-world data, our findings suggest that the use of everolimus may favorably impact overall survival, and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8573446/

Efficacy and safety of low-dose everolimus combined with ... The results revealed drug effectiveness of 29.8% and 27.8%, and PFSs of 9 and 10 months in Groups A and B, respectively, thus suggesting no significant ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2783528

Effectiveness of Adding Everolimus to ... In the present study, the addition of everolimus to letrozole resulted in a significantly longer median PFS in the intention-to-treat population ...

4. novartis.com novartis.com/us-en/news/media-releases/novartis-drug-afinitor-helps-women-advanced-breast-cancer-live-significantly-longer-without-their-disease-progressing

Novartis Drug Afinitor® Helps Women With Advanced ... Everolimus combined with hormonal therapy more than doubled time without tumor growth and reduced risk of progression by 57% vs hormonal therapy alone(1)-- ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1109653

Everolimus in Postmenopausal Hormone-Receptor ... Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor–positive advanced breast cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5214808/

Safety, Efficacy, and Patient Acceptability of Everolimus in the ... These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent ...

7. clinical-breast-cancer.com clinical-breast-cancer.com/article/S1526-8209(13)00185-7/fulltext

Safety and Efficacy of Everolimus With Exemestane vs. ... Conclusion. Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR+ advanced breast cancer.

8. valueinhealthjournal.com valueinhealthjournal.com/article/S1098-3015(18)30388-7/fulltext

Efficacy and Safety of Everolimus in the Treatment ... Everolimus showed significant improvement in OS and PFS in patients with mBCa when compared to control. In addition, everolimus was associated with lower ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)57720-1/fulltext

Safety and efficacy of everolimus (EVE) plus exemestane ... Results. A total of 235 pts received EVE+EXE therapy. The overall safety analysis were similar to results previously reported for EVE+EXE. AEs were the main ...