Hydroxychloroquine + Abemaciclib for Breast Cancer

(ABBY Trial)

Overseen By Lauren Bayne, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center at Penn Medicine

Must not be taking: Tamoxifen

Disqualifiers: Pregnancy, Major surgery, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 6

Duration: 6 months

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two medications, hydroxychloroquine and abemaciclib (a cancer treatment drug), can reduce or eliminate cancer cells in the bone marrow of people with breast cancer. Both medications are taken in pill form twice daily and have FDA approval for other uses. The trial suits individuals who have completed their main breast cancer treatments, show no signs of cancer returning, but have detectable cancer cells in their bone marrow. Participants should not have used tamoxifen recently due to potential interactions with hydroxychloroquine. As a Phase 2 trial, this 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 all current medications, but you cannot take tamoxifen due to interactions with hydroxychloroquine. You can continue adjuvant endocrine and bone modifying agents as per standard care guidelines.

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

Research has shown that abemaciclib is generally safe, with manageable and temporary side effects. Studies have found that patients typically handle these side effects well, with no major long-term safety concerns. The FDA has already approved this drug for certain types of breast cancer, supporting its safety profile.

For hydroxychloroquine, research has demonstrated its safety and tolerability at doses up to 800 mg per day, even when combined with other cancer treatments. It is also FDA-approved for conditions like malaria and certain autoimmune diseases, indicating its general safety for humans.

Both drugs have undergone previous testing and are considered safe for people. This trial explores whether using them together can effectively treat breast cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for breast cancer, which primarily focus on hormone therapy, chemotherapy, or targeted therapy, the combination of Abemaciclib and Hydroxychloroquine offers a fresh approach. Abemaciclib is a CDK4/6 inhibitor that prevents cancer cells from dividing and growing, while Hydroxychloroquine, traditionally used to treat malaria, may enhance the effectiveness of cancer drugs by interfering with certain cellular processes. Researchers are excited about this combination because it targets cancer cells differently and may overcome resistance issues seen with other treatments, potentially leading to more effective outcomes for patients.

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

Research has shown that abemaciclib, one of the treatments in this trial, effectively treats breast cancer. In patients with high-risk early breast cancer, it reduced the chance of recurrence and extended survival. Studies also found that it prolongs life when used as the first treatment for advanced breast cancer. This trial will compare abemaciclib alone with a combination of abemaciclib and hydroxychloroquine. Early results suggest this combination might enhance treatment effectiveness, especially with hormone-blocking therapies. Overall, abemaciclib, whether used alone or with hydroxychloroquine, shows promise for improving breast cancer treatment outcomes. ^{4 6 7 8 9}

Who Is on the Research Team?

Amy Clark

Principal Investigator

Abramson Cancer Center at Penn Medicine

Are You a Good Fit for This Trial?

This trial is for adults who've had invasive breast cancer diagnosed within the last 5 years and have finished primary treatments, except endocrine therapy. They must not show signs of cancer recurrence, be able to take oral meds, and meet specific health criteria like good organ function. Pregnant women or those not using birth control are excluded.

Inclusion Criteria

You have specific characteristics in your breast cancer that put you at a higher risk, such as certain receptor levels or lymph node status.

My breast cancer was confirmed by a biopsy and diagnosed within the last 5 years.

Exclusion Criteria

Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study

I started taking medication for bone health less than 3 months ago.

You are allergic to hydroxychloroquine or similar medicines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib and/or Hydroxychloroquine to target disseminated tumor cells in bone marrow

6 months

6 cycles of treatment

Safety Assessment

Incidence of treatment-emergent adverse events during cycle 1 of the safety cohort

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Hydroxychloroquine

Trial Overview The study compares hydroxychloroquine (Plaquenil) and abemaciclib (Verzenio), both FDA-approved drugs taken as pills twice daily. It aims to see if these can reduce or eliminate disseminated tumor cells in bone marrow after standard treatment for breast cancer.

How Is the Trial Designed?

Group I: B (Abema + HCQ) Experimental Treatment 2 Interventions

Abemaciclib (100 mg or 150 mg BID\*) + Hydroxychloroquine (600 mg BID) \*Abemaciclib dose will be determined by safety cohort

Group II: A (Abema) Experimental Treatment 1 Intervention

Abemaciclib (150 mg BID)

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

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

In a phase III study involving postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the addition of abemaciclib to endocrine therapy significantly improved progression-free survival (PFS) compared to placebo, with a median PFS not reached versus 14.7 months in cohort A, and 11.5 months versus 5.6 months in cohort B.

Abemaciclib also demonstrated a higher objective response rate (ORR) of 65.9% in cohort A and 50.0% in cohort B compared to 36.1% and 10.5% in the placebo groups, respectively, indicating its efficacy in treating this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study. Zhang, QY., Sun, T., Yin, YM., et al.[2022]

Abemaciclib is a potent oral CDK4 and CDK6 inhibitor that effectively treats hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, showing response rates between 19.7% and 59% in major clinical trials.

The drug is well-tolerated, with common side effects including diarrhea and neutropenia, and it offers the advantage of continuous dosing and potential use as a monotherapy, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. Palumbo, A., Lau, G., Saraceni, M.[2020]

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

Abemaciclib combined with endocrine therapy (ET) significantly improves quality-adjusted life years (QALYs) in patients with high-risk hormone receptor positive, HER2-negative early breast cancer, with an increase of 0.99 QALYs compared to ET alone.

The treatment is considered cost-effective in Italy, with an incremental cost-effectiveness ratio of €22,651 per QALY gained, and a 99% likelihood of being cost-effective at a threshold of €30,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. Davie, A., Traoré, S., Giovannitti, M., et al.[2023]

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

In patients with hormone receptor-positive, HER2-negative metastatic breast cancer who progressed on palbociclib, those without CDK4/6 inhibitor resistance mutations (CDKi-R[-]) had a median progression-free survival (PFS) of 7.0 months on abemaciclib, compared to just 3.5 months for those with mutations (CDKi-R[+]), indicating that the presence of these mutations significantly impacts treatment efficacy.

This study is the first to identify a genomic panel that may help predict sensitivity to abemaciclib in patients with ESR1 mutations after progression on palbociclib, suggesting that further research could refine this panel to better guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Gene Panel Associated With Abemaciclib Utility in ESR1-Mutated Breast Cancer After Prior Cyclin-Dependent Kinase 4/6-Inhibitor Progression. Brett, JO., Dubash, TD., Johnson, GN., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12550314/

metastatic breast cancer: A propensity-matched ... In this large, real-world cohort study, first-line abemaciclib was associated with a significant overall survival benefit compared to ...

2. prnewswire.com prnewswire.com/news-releases/lillys-verzenio-abemaciclib-prolonged-survival-in-hr-her2--high-risk-early-breast-cancer-with-two-years-of-treatment-302586849.html

Lilly's Verzenio® (abemaciclib) prolonged survival in HR+, ... In high-risk EBC, Verzenio has shown a persistent and deepening benefit beyond the two-year treatment period in the monarchE trial, an adjuvant ...

3. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/verzenio-kisqali-positive-long-term-results-early-breast-cancer-trials

Verzenio and Kisqali Deliver Positive Long-Term Results ... Verzenio plus endocrine therapy reduced the risk of death by 15.8% versus ET alone in high-risk HR+/HER2– early breast cancer.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01994

Results From a Preplanned monarchE Overall Survival ... Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and ...

5. verzenio.lilly.com verzenio.lilly.com/hcp/efficacy-early-breast-cancer

Verzenio® + ET for Early Breast Cancer | Efficacy - Eli Lilly At Month 24, Verzenio plus ET was 92.6% vs ET alone at 89.4%—a 2-year delta of 3.2%. At Month 36, Verzenio plus ET was 88.9% vs ET alone at 83.7%—a 3-year delta ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03155997

Study Details | NCT03155997 | Endocrine Therapy With or ... The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0923753425049488

Overall Survival with Abemaciclib in Early Breast Cancer Patient reported outcomes findings confirm a tolerable and reversible toxicity profile. The long-term safety data compiled did not support any ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601722/

Clinical Review - Abemaciclib (Verzenio) - NCBI Bookshelf - NIH Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10730497/

Metastatic Breast Cancer Receiving Abemaciclib in ... The efficacy and safety of abemaciclib among patients with HR+/HER2− mBC has been demonstrated in the MONARCH clinical trials; however, there is ...