Abemaciclib for Head and Neck Cancer

No longer recruiting at 2 trial locations

Overseen By Rachel Jarrett, MPH

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arizona

Must not be taking: CDK 4/6 inhibitors, PD-1/L1 inhibitors

Disqualifiers: Autoimmune disorders, Cardiac abnormalities, Active infections, others

Stay on Your Current Meds You can continue your current medications while participating

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: 1

Duration: 10-28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of a new drug, abemaciclib (also known as Verzenio), on HPV-negative head and neck cancer. The goal is to evaluate the drug's efficacy before surgery and to understand its effects on the body. This trial seeks participants with HPV-negative head and neck cancer who have not yet received treatment. Participants should have measurable tumors and plan to have them surgically removed. As a Phase 2 trial, the research focuses on assessing 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 must stop taking your current medications. However, if you are on drugs that strongly affect liver enzymes (CYP3A), you may need to stop them at least 7 days before starting the trial, unless a suitable substitute is found.

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

Research has shown that abemaciclib is already used for some types of cancer, indicating its safety is well understood. In various studies, the most common side effects included diarrhea, nausea, fatigue, and a decrease in white blood cells, known as neutropenia. Despite these side effects, most patients continued taking the medication. In past studies, about 19% of patients stopped using abemaciclib due to side effects. This suggests that while side effects can occur, many patients find them manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for head and neck cancer, which often include surgery, radiation, and chemotherapy, abemaciclib offers a more targeted approach. Abemaciclib is a CDK4/6 inhibitor, which means it specifically targets proteins involved in cell division, potentially slowing down the growth of cancer cells. This precision allows it to work differently from traditional chemotherapy, which can affect both cancerous and healthy cells. Researchers are excited about abemaciclib because it might offer a more effective treatment with potentially fewer side effects, and it can show results in just 10-21 days, which is faster than many current options.

What evidence suggests that abemaciclib might be an effective treatment for head and neck cancer?

Research shows that abemaciclib may help treat different types of cancer. For head and neck cancer, studies have found that it can delay disease progression and extend patients' lives. In other cancers, like breast cancer, it has significantly prolonged survival. This success raises hope for its effectiveness in head and neck cancer as well. The drug blocks certain proteins that promote cancer cell growth, which is why researchers are testing it for various cancers. Participants in this trial will receive abemaciclib to evaluate its effectiveness specifically for head and neck cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Ricklie A. Julian

Principal Investigator

University of Arizona

Are You a Good Fit for This Trial?

This trial is for adults with HPV-negative head and neck squamous cell carcinoma (HNSCC) who have not been treated before. They must be physically well enough to participate, able to swallow pills, and have no serious heart or lung conditions. Patients with certain previous cancers can join if they've been cancer-free for 2 years. Women of childbearing potential must use effective contraception.

Inclusion Criteria

My cancer can be measured by scans or physical tools.

I have not received any treatment for my head and neck cancer.

You agree to provide tissue samples for research purposes, including a biopsy of the tumor before and during surgery.

Exclusion Criteria

Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.

Active or previously documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, Wegener syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.). The following are exceptions to this criterion: Patients with vitiligo or alopecia Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. Subclinical hypothyroidism (eg. Elevated thyroid-stimulating hormone (TSH), low or normal free T4, and asymptomatic) observed on screening labs is not an exclusion. Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the study PI Patients with celiac disease controlled by diet alone

I have not taken any CDK 4/6 or PD-1/L1 inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant abemaciclib for 10-21 days, with a possible extension up to 28 days due to surgical delays

10-28 days

Daily administration

Surgery

Participants undergo planned oncologic surgery after the treatment phase

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including biomarker analysis and tumor size assessment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Nivolumab

Trial Overview The AIM Trial is testing the effects of a drug called Abemaciclib in patients with specific types of HNSCC that are HPV-negative. It's an open label Phase II trial where all participants receive the drug before their planned surgery to remove the tumor.

How Is the Trial Designed?

Group I: Treatment with abemaciclib Experimental Treatment 1 Intervention

Treatment will consist of a single neoadjuvant cycle of 10-21 days (+7 days if needed due to surgical delay). Abemaciclib will be administered from days 1-21. Abemaciclib may be continued for an additional 7 days, or up to 28 days, for delays in planned surgery. Abemaciclib 200 mg PO twice daily on Days 1-21 (+7 days).

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

George Washington University

Collaborator

Trials

263

Recruited

476,000+

Published Research Related to This Trial

The JAVELIN Head and Neck 100 study is a Phase III clinical trial investigating the effectiveness of avelumab, a PD-L1 inhibitor, combined with standard chemoradiotherapy (CRT) for high-risk, locoregionally advanced squamous cell carcinomas of the head and neck.

This study addresses a critical gap in research, as there are currently no prospective studies evaluating immune checkpoint inhibitors in the definitive treatment of nonmetastatic HNSCC, which is important for improving outcomes in patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAVELIN Head and Neck 100: a Phase III trial of avelumab and chemoradiation for locally advanced head and neck cancer. Yu, Y., Lee, NY.[2020]

Nivolumab, a PD-1 inhibitor, has been FDA-approved for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) after platinum-based therapy, but treatment options remain limited for these patients.

A case study of a 46-year-old male with refractory HNSCC showed successful treatment using a combination of nivolumab and ipilimumab, suggesting potential efficacy for this combination therapy in HNSCC, similar to its success in metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. Schwab, KS., Kristiansen, G., Schild, HH., et al.[2022]

The maximally tolerated dose (MTD) of afatinib when combined with carboplatin and paclitaxel for treating head and neck squamous cell carcinoma is determined to be 20 mg daily, as higher doses led to severe toxicities.

In a trial with nine patients, five showed a partial response and two had stable disease after induction chemotherapy, indicating some efficacy of the treatment combination, but caution is advised due to significant adverse effects at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma. Chung, CH., Rudek, MA., Kang, H., et al.[2018]

In a phase II trial involving 41 patients with operable head and neck squamous cell carcinoma (HNSCC), preoperative treatment with olaparib, either alone or in combination with cisplatin or durvalumab, was found to be safe and resulted in a significant reduction in tumor cell proliferation, as indicated by a decrease in Ki67 of at least 25% in 44.8% of treated patients.

The treatment also modulated the tumor microenvironment, leading to increased levels of PD-L1 and changes in macrophage polarization, suggesting that combining olaparib with other therapies may enhance its antitumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer. Moutafi, M., Koliou, GA., Papaxoinis, G., et al.[2023]

In the phase II HAWK study involving 112 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) who had high PD-L1 expression, durvalumab showed an objective response rate of 16.2%, with a notably higher rate of 29.4% in HPV-positive patients.

Durvalumab was found to have an acceptable safety profile, with 57.1% of patients experiencing treatment-related adverse events, but none were fatal, indicating it could be a viable treatment option for this difficult-to-treat patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. Zandberg, DP., Algazi, AP., Jimeno, A., et al.[2020]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.6044

Abemaciclib in recurrent/metastatic head and neck ... 1.1. Secondary endpoints included best overall response rate (BORR), progression free survival (PFS), overall survival (OS) and adverse event ( ...

2. targetedonc.com targetedonc.com/view/abemaciclib-significantly-improves-overall-survival-in-high-risk-early-breast-cancer

Abemaciclib Significantly Improves Overall Survival in High ... The CDK4/6 inhibitor abemaciclib (Verzenio) has demonstrated a statistically significant improvement in overall survival (OS) when ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9842704/

Targeted therapy for head and neck cancer - PubMed Central The addition of cetuximab to platinum-based chemotherapy increased the median overall survival (OS) to 10.1 months, which makes the EXTREME ...

4. oncpracticemanagement.com oncpracticemanagement.com/special-issues/the-evolution-of-abemaciclib-clinical-trial-data-for-the-treatment-of-hr-positive-her2-negative-metastatic-breast-cancer

The Evolution of Abemaciclib Clinical Trial Data for ... PFS was significantly improved with the combination of abemaciclib plus fulvestrant of 16.9 months compared with 9.3 months with fulvestrant (hazard ratio, ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1437380/full

Abemaciclib treatment patterns and outcome in HR+/HER2 ... Conclusion: The present real-world evidence confirms the feasibility and effectiveness, in terms of response rate and PFS, of abemaciclib in ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/abemaciclib-oral-route/description/drg-20406567

Abemaciclib (oral route) - Side effects & dosage It interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells may also be affected by the ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/208716s006s007s008lbl.pdf

VERZENIO® (abemaciclib) tablets, for oral use The most common adverse reactions (incidence ≥20%) across clinical trials were: diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, ...

8. oncologynewscentral.com oncologynewscentral.com/drugs/monograph/174190-317058/abemaciclib-oral

Abemaciclib: uses, dosing, warnings, adverse events, ... Head & Neck Cancer · Hematologic Malignancies · Hepatocellular Carcinoma (HCC) ... safety data and dosage reduction rates. All patients enrolled in the ...

9. verzenio.lilly.com verzenio.lilly.com/hcp/safety-adverse-reactions

Adverse Reactions | HCP Safety | Verzenio (abemaciclib) Adverse reactions (ARs) were consistent with the known safety profile for Verzenio · In the monarchE trial, ~81% did NOT discontinue Verzenio due to ARs · 19% of ...

10. pi.lilly.com pi.lilly.com/ca/verzenio-ca-pm.pdf

Product Monograph Including Patient Medication Information The safety of VERZENIO has been assessed in patients from three randomized Phase 3 studies and one single-arm Phase 2 study of patients with HR-positive, HER2- ...