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

Trial Summary

What is the purpose of this trial?

This is a Phase II randomized, controlled, open label breast cancer clinical trial. 66 patients will be enrolled. The drugs being studied are hydroxychloroquine (Plaquenil) and abemaciclib (also Verzenio). This research study is testing whether using these drugs to target the disseminated tumor cells in bone marrow can reduce their number or eliminate them. Both hydroxychloroquine and abemaciclib are pills that will be taken twice daily. Both are approved by the FDA

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.

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

Research shows that Abemaciclib, when combined with endocrine therapy, is effective in reducing the risk of breast cancer recurrence in patients with hormone receptor-positive, HER2-negative breast cancer. It has also been shown to improve progression-free survival in advanced breast cancer when used as a first-line therapy. ^{1 2 3 4 5}

What makes the drug combination of Hydroxychloroquine and Abemaciclib unique for breast cancer treatment?

This drug combination is unique because it combines Hydroxychloroquine, which is traditionally used for malaria and autoimmune diseases, with Abemaciclib, a CDK4/6 inhibitor that targets specific proteins involved in cell division. This combination may offer a novel approach for patients with hormone receptor-positive, HER2-negative breast cancer, especially after progression on other CDK4/6 inhibitors. ^{1 3 4 5 6}

Research Team

Amy Clark

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

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.

Patients must have completed all primary therapy (definitive surgery, (neo)adjuvant chemotherapy adjuvant radiation and/or Her2-directed therapy) for the index malignancy at least 4 weeks prior to study entry. Prior treatment-related toxicity must be resolved or improving to Grade 1 with the exception of alopecia, Grade 2 endocrine disorders (e.g. adrenal insufficiency or thyroid disorders from prior immunotherapy) controlled on stable replacement therapy for > 1 year, and up to Grade 3 peripheral neuropathy, prior to study enrollment. Concurrent receipt of adjuvant endocrine and bone modifying agents is allowed per standard of care guidelines. Tamoxifen is not allowed due to drug-drug interactions with HCQ. Bone marrow aspirate obtained via research trial UPCC 28115 after completion of therapy (except endocrine therapy) demonstrates detectable DTCs (via IHC). No evidence of recurrent local or distant breast cancer by physical examination, blood tests (CBC, LFTs, Alk Phos), or imaging. Assessment for overt metastatic disease by radiologic testing per institutional guidelines (CT Chest, Abdomen and Pelvis, bone scan, MRI and/or PET/CT) will only be done in patients with DTCs detected on bone marrow aspirate who are being screened for this trial. Age >/= 18 years. ECOG performance status =/< 2. Ability to swallow oral medications. No contraindications to the study medications or uncontrolled medical illness. Adequate bone marrow function as shown by: ANC >/= 1.5 x 10^9/L, Platelets >/= 100 x 10^9/L, Hb >9 g/dL. Adequate liver function as shown by: Serum bilirubin </= 1.5 x ULN, ALT and AST </= 3.0 x ULN, and INR </=1.5. Adequate renal function: serum creatinine </= 1.5 x ULN. Adequate muscle function: creatinine phosphokinase (CPK) </= 2.5 x ULN. Anticoagulation is allowed if target INR =/< 1.5 on a stable dose of warfarin or on a stable dose of anticoagulant for >2 weeks at time of randomization. Ability to provide informed consent

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.

I am not taking tamoxifen for my hormone-receptor positive breast cancer due to its interaction with hydroxychloroquine.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

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

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

3. Italy 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. [2023]

4. England 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. [2022]

5. United States 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. [2023]

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

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. [2020]