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

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

53 Participants Needed

Trial Summary

What is the purpose of this trial?

To evaluate the feasibility of administering HCQ, EVE or the combination in patients who have completed primary therapy for breast cancer and harbor bone marrow disseminated tumor cells.

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.

What data supports the effectiveness of the drug combination of Hydroxychloroquine and Everolimus for breast cancer?

Research shows that Everolimus, when combined with other therapies, can improve outcomes in hormone receptor-positive, HER2-negative advanced breast cancer by extending the time patients live without the disease getting worse. ^{1 2 3 4 5}

Is the combination of Hydroxychloroquine and Everolimus generally safe for humans?

Everolimus is generally well tolerated in humans, with common side effects like mouth sores, rash, tiredness, high blood sugar, and high cholesterol, which are usually mild and manageable. However, it can sometimes cause serious lung inflammation. Hydroxychloroquine is not mentioned in the provided research, so its safety profile in combination with Everolimus is not detailed here. ^{1 6 7 8 9}

How does the drug combination of Hydroxychloroquine and Everolimus differ from other breast cancer treatments?

The combination of Hydroxychloroquine and Everolimus for breast cancer is unique because it pairs an antimalarial drug (Hydroxychloroquine) with Everolimus, which is known to inhibit a specific protein complex (mTORC1) involved in cancer cell growth. This combination may offer a novel approach by potentially enhancing the effectiveness of Everolimus through the addition of Hydroxychloroquine, which is not a standard component in breast cancer treatment. ^{1 5 10 11 12}

Research Team

Angela DeMichele, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Cyprus pubmed.ncbi.nlm.nih.gov

Efficacy of everolimus combined with endocrine therapy in HR-positive/HER-2-negativeadvanced breast cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Evaluating everolimus for the treatment of breast cancer. [2023]

3. Italy 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. [2021]

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

Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study. [2022]

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

Fulvestrant Plus Vistusertib vs Fulvestrant Plus Everolimus vs Fulvestrant Alone for Women With Hormone Receptor-Positive Metastatic Breast Cancer: The MANTA Phase 2 Randomized Clinical Trial. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

Everolimus: side effect profile and management of toxicities in breast cancer. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma. [2022]

9. Italy pubmed.ncbi.nlm.nih.gov

Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: results of phase IIIb BALLET trial in Spain. [2018]

10. Netherlands 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. [2018]

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

Case report: 5-year progression free survival and complete liver response in a patient with metastatic breast cancer treated with everolimus plus exemestane. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Safety analysis, association with response and previous treatments of everolimus and exemestane in 181 metastatic breast cancer patients: A multicenter Italian experience. [2019]