Palbociclib + Chemoradiation for Head and Neck Cancer

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

26 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the results of treating patients with HPV-unrelated head and neck squamous cell carcinoma with neoadjuvant single-agent palbociclib, followed by chemoradiation (either cisplatin + IMRT or cetuximab + IMRT depending on patient characteristics), followed by adjuvant single-agent palbociclib.

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.

What data supports the effectiveness of the treatment Palbociclib + Chemoradiation for Head and Neck Cancer?

Research shows that intensity-modulated radiation therapy (IMRT) combined with cetuximab is effective for treating head and neck cancer, as cetuximab has been shown to be superior to radiation therapy alone. However, studies comparing cetuximab to cisplatin (another chemotherapy drug) suggest that cisplatin may lead to better outcomes in some cases. ^{1 2 3 4 5}

Is the combination of Palbociclib, Cetuximab, and Chemoradiation safe for treating head and neck cancer?

Cetuximab combined with radiation therapy has been shown to provide benefits without increasing radiation-related side effects, but it can cause serious skin reactions in some patients. Chemoradiotherapy with cisplatin is effective but can lead to severe side effects, suggesting the need for more tolerable treatment options. ^{2 6 7 8 9}

How does the drug Palbociclib combined with chemoradiation differ from other treatments for head and neck cancer?

Palbociclib is a unique drug because it targets specific proteins involved in cell division, potentially enhancing the effectiveness of chemoradiation therapy for head and neck cancer. This combination may offer a novel approach compared to traditional treatments like cetuximab or platinum-based therapies, which have been associated with significant toxicities. ^{2 6 8 9 10}

Research Team

Douglas R. Adkins

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

Phase I Trial of Cetuximab, Radiotherapy, and Ipilimumab in Locally Advanced Head and Neck Cancer. [2023]

2. France pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. [2021]

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

Concurrent Chemoradiotherapy With Cisplatin Versus Cetuximab for Squamous Cell Carcinoma of the Head and Neck. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

A matched-pair comparison of intensity-modulated radiation therapy with cetuximab versus intensity-modulated radiation therapy with platinum-based chemotherapy for locally advanced head neck cancer. [2021]

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

Trends in chemoradiation use in elderly patients with head and neck cancer: Changing treatment patterns with cetuximab. [2022]

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

Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. [2015]

8. England 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? [2015]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced head and neck cancer (LAHNSCC). [2022]

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

Concurrent cetuximab versus platinum-based chemoradiation for the definitive treatment of locoregionally advanced head and neck cancer. [2019]