Palbociclib + Chemoradiation for Head and Neck Cancer

Not currently recruiting at 1 trial location

Overseen By Douglas R Adkins, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Strong CYP3A4 inhibitors, QT prolonging drugs

Disqualifiers: Metastatic disease, Other malignancy, HIV, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a combination of treatments for individuals with a type of head and neck cancer not linked to HPV. Participants will first receive palbociclib, a drug that inhibits cancer cell growth, followed by chemoradiation, and then additional palbociclib. Two treatment paths are available: one combines cisplatin (a chemotherapy drug) with radiation, and the other combines cetuximab (a targeted therapy) with radiation. Suitable candidates have specific types of head and neck cancer not caused by HPV and have been diagnosed with stages III or IV of the disease. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, specifically strong CYP3A4 inhibitors or inducers, drugs that prolong the QT interval, and proton pump inhibitors, at least 7 days before starting the trial. If you are on these medications, you will need to discuss alternatives with your doctor.

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

Research has shown that palbociclib is usually well-tolerated by patients with head and neck cancer. When combined with cetuximab, its side effects resemble those seen in other conditions and remain manageable.

Cisplatin, used with intensity-modulated radiation therapy (IMRT), proves effective and safe. Studies indicate that both weekly and every-three-week doses of cisplatin yield similar safety results for patients with head and neck cancer. However, higher doses can lead to hearing loss, which is important to consider.

Cetuximab, when used with IMRT, effectively treats head and neck cancers. Research shows it can significantly improve survival rates when added to radiation therapy. Its side effects are generally manageable and well-documented.

Overall, these treatments are considered safe in clinical settings, but participants should be aware of possible side effects like hearing changes with cisplatin and skin reactions with cetuximab. Always discuss any concerns with a healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of palbociclib with chemoradiation for head and neck cancer because it offers a fresh approach to treatment. Unlike standard options like just chemotherapy and radiation, this treatment includes palbociclib, a targeted therapy that inhibits a specific protein involved in cancer cell growth, potentially enhancing effectiveness. The trial also explores two combinations: one with cisplatin and the other with cetuximab, both paired with intensity-modulated radiation therapy (IMRT). These combinations aim to optimize cancer control while potentially reducing side effects associated with traditional treatments.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research shows that palbociclib may help treat head and neck cancer. Studies indicate that 40% of patients with this cancer type experienced some benefit from the treatment. In this trial, participants in Cohort 1 will receive palbociclib combined with cisplatin and IMRT. Previous research found that using cisplatin with a specific type of radiation therapy (IMRT) at a total dose of at least 200 mg/m² can improve survival rates. Meanwhile, participants in Cohort 2 will receive palbociclib combined with cetuximab and IMRT. Studies have shown that using cetuximab with radiation therapy significantly increases survival rates for patients with advanced head and neck cancer. These findings suggest that combining these treatments might effectively manage head and neck squamous cell carcinoma. ^{2 3 6 7 8}

Who Is on the Research Team?

Douglas R. Adkins

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults with stage III/IV HPV-unrelated head and neck squamous cell carcinoma, who have not received prior systemic therapy for it. They must have measurable disease, normal bone marrow function, adequate organ function, and agree to use contraception. Excluded are those with distant metastasis, certain drug interactions or allergies, pregnant/breastfeeding women, HIV-positive on antiretroviral therapy, other recent malignancies (except some skin/prostate/thyroid/cervical cancers), or uncontrolled illnesses.

Inclusion Criteria

Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

-- Bilirubin 1.5-2 x IULN

I can walk and take care of myself, but I cannot do any work.

Exclusion Criteria

My cancer has spread to distant parts of my body.

I am not taking any proton pump inhibitors.

I do not have any serious illnesses that are not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Palbociclib Monotherapy

Participants receive neoadjuvant single-agent palbociclib (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)

8 weeks

Concurrent Chemoradiation Therapy

Participants receive either cisplatin + IMRT or cetuximab + IMRT depending on patient characteristics, administered over 6 weeks

6 weeks

Adjuvant Palbociclib Monotherapy

Participants receive adjuvant single-agent palbociclib (125 mg/day, days 1-21 of each 28-day cycle for six cycles)

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Cisplatin
• Intensity-Modulated Radiation Therapy
• Palbociclib

Trial Overview The trial tests the effectiveness of palbociclib monotherapy before and after chemoradiation therapy in patients with specific head and neck cancer. Chemoradiation involves cisplatin plus IMRT or cetuximab plus IMRT based on patient characteristics. The study aims to see how well patients respond to this treatment sequence.

How Is the Trial Designed?

Group I: Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib Experimental Treatment 5 Interventions

* Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles) * Step 2: Cetuximab given one week before RT and then weekly with accelerated IMRT 70 Gy to be administered over 6 weeks * Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cetuximab \& IMRT

Group II: Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib Experimental Treatment 5 Interventions

* Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles) * Step 2: Cisplatin 100 mg/m\^2 given on Days 1 and 22 with accelerated IMRT 70 Gy to be administered over 6 weeks * Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cisplatin \& IMRT

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a study of 174 patients with locally advanced head and neck cancer, those treated with cisplatin (CDDP) showed significantly better outcomes compared to those treated with cetuximab (C225) in terms of loco-regional failure, disease-free survival, and overall survival, with P-values indicating strong statistical significance (P<0.0001).

Even after accounting for HPV status in a subset of 62 patients, cisplatin still demonstrated superior efficacy, reinforcing the conclusion that CDDP is a more effective treatment option than C225 for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Chemoradiotherapy With Cisplatin Versus Cetuximab for Squamous Cell Carcinoma of the Head and Neck. Riaz, N., Sherman, E., Koutcher, L., et al.[2022]

In a study comparing cisplatin and cetuximab added to radiation therapy for head and neck squamous cell carcinoma, patients receiving cisplatin had a significantly higher 3-year disease-specific survival rate of 83% compared to 31% for those receiving cetuximab.

Cisplatin treatment was associated with a lower recurrence rate of disease (4 patients) compared to cetuximab (17 patients), indicating that cisplatin may be more effective in improving outcomes when combined with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. Ley, J., Mehan, P., Wildes, TM., et al.[2021]

Adding the EGFR inhibitor cetuximab to radiotherapy for locally advanced squamous cell carcinoma of the head and neck significantly improves clinical outcomes without increasing the toxicity associated with radiotherapy.

Current chemoradiotherapy regimens, which are often platinum-based, have reached a limit in tolerable toxicity, highlighting the need for more effective and tolerable treatment options like cetuximab combined with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squamous cell carcinomas of the head and neck? Bernier, J., Schneider, D.[2015]

The use of chemoradiation therapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) significantly increased from 29% in 2001 to 61% in 2009, indicating a growing acceptance of this treatment approach.

Since the approval of cetuximab in 2006, it has become the most commonly used agent in CRT, suggesting that it may have contributed to the increased use of CRT, particularly among older and sicker patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in chemoradiation use in elderly patients with head and neck cancer: Changing treatment patterns with cetuximab. Baxi, SS., O'Neill, C., Sherman, EJ., et al.[2022]

In a study of 99 head-and-neck cancer patients receiving simultaneous integrated boost intensity-modulated radiotherapy with cetuximab, 34% experienced severe dermatitis (Grade 3/4), significantly higher than the 3% in a control group treated with cisplatin.

There was a clear link between the radiation dose to the skin and the severity of dermatitis in patients receiving cetuximab, indicating that higher radiation exposure increases the risk of severe skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. Studer, G., Brown, M., Salgueiro, EB., et al.[2015]

In a study of 180 patients with head and neck cancer, those treated with cetuximab experienced significantly higher rates of acute dermal toxicity (34.5%) compared to those who did not receive cetuximab (10.3%).

Despite the increased skin toxicity, there were no significant differences in local control or overall survival between patients treated with cetuximab and those treated without it, indicating that cetuximab does not improve survival outcomes when combined with IMRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer. Bibault, JE., Morelle, M., Perrier, L., et al.[2022]

The recommended phase II dose (RP2D) of ipilimumab, when added to standard cetuximab and radiotherapy for high-risk head and neck squamous carcinoma, is established at 1 mg/kg, demonstrating a tolerable safety profile with manageable adverse effects.

The combination treatment resulted in a promising 3-year disease-free survival and overall survival rate of 72%, indicating its efficacy without the need for cytotoxic chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Cetuximab, Radiotherapy, and Ipilimumab in Locally Advanced Head and Neck Cancer. Ferris, RL., Moskovitz, J., Kunning, S., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39869839/

Correlates of Cetuximab Efficacy in Recurrent and ... Results: We identified 70 patients treated with cetuximab after an ICI. The mean age was 67.6 years, with 60% having virus-associated HNSCC.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa0802656

Platinum-Based Chemotherapy plus Cetuximab in Head ... Cetuximab is effective in recurrent or metastatic squamous-cell carcinoma of the head and neck that progresses despite platinum-containing therapy.

3. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/head-neck-cancer-cetuximab-versus-durvalumab

Cetuximab Outperforms Durvalumab for Head and Neck ... At a median follow-up of 2.3 years, 64% of those in the cetuximab group were alive and free of disease progression, a measure known as ...

4. news.bms.com news.bms.com/news/details/2008/ERBITUXR-Five-Year-Data-Show-Significant-Improvement-in-Overall-Survival-for-Patients-with-Locally-or-Regionally-Advanced-Head-and-Neck-Cancer/default.aspx

ERBITUX(R) Five-Year Data Show Significant ... These five-year data demonstrate that the addition of ERBITUX to radiation therapy resulted in a significant increase in median overall survival for patients ...

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10440-7

Treatment outcomes of cetuximab-containing regimen in ... In EXTREME study, by incorporating cetuximab with platinum and fluorouracil, the risk of death significantly decreased by 20%, the risk of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33751752/

Safety and Efficacy of Cetuximab-Based Salvage ... Cetuximab-based salvage chemotherapy (SCAI) achieved high response rates in patients with recurrent/metastatic squamous cell cancer of the head and neck ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00122460

Study Details | NCT00122460 | Cetuximab (Erbitux) in ... The purpose of this trial is to investigate the efficacy of cetuximab in combination with chemotherapy in comparison to chemotherapy alone in patients with ...

8. ascopubs.org ascopubs.org/doi/10.1200/GO.24.00059

Efficacy and Safety of Biosimilar Cetuximab Versus ... This trial compared the efficacy and safety of biosimilar cetuximab versus innovator cetuximab (IC) in combination with platinum-based chemotherapy in patients ...