Palbociclib + Cetuximab for Head and Neck Cancer

Recruiting at 1 trial location

Overseen By Douglas R. Adkins

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Washington University School of Medicine

Must not be taking: CYP3A4 inhibitors, inducers

Disqualifiers: Cetuximab, CDK4/6 inhibitors, Rb loss, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

81 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that certain HIV medications may need to be avoided due to potential drug interactions. It's best to discuss your current medications with the trial team.

Is the combination of Palbociclib and Cetuximab safe for humans?

Cetuximab is generally considered safe and well-tolerated, with common side effects being mild skin issues. It has been used safely in treatments for colorectal and head and neck cancers. ^{1 2 3 4 5}

What makes the drug combination of Palbociclib and Cetuximab unique for head and neck cancer?

The combination of Palbociclib and Cetuximab is unique because it targets the epidermal growth factor receptor (EGFR) with Cetuximab, a monoclonal antibody, while Palbociclib, a CDK4/6 inhibitor, may help control cell division, offering a novel approach compared to traditional chemotherapy or radiotherapy alone. ^{3 6 7 8 9}

What is the purpose of this trial?

This multicenter, open-label, randomized phase 3 trial will determine if palbociclib and cetuximab (Arm 1) improves overall survival (OS) in comparison to cetuximab monotherapy (Arm 2) in patients with CDKN2A-altered, HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who experienced disease progression on a PD-1/L1 inhibitor (given as monotherapy or in combination with other therapy).

Research Team

Douglas R. Adkins

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with CDKN2A-altered, HPV-unrelated head and neck squamous cell carcinoma who have had disease progression after treatment with a PD-1/L1 inhibitor. They should not have received more than three prior therapies, must be in good physical condition (ECOG ≤ 1), and have proper organ function. Pregnant women are excluded, and participants must agree to use contraception.

Inclusion Criteria

I have had up to three treatments for my head and neck cancer.

My bone marrow and organs are functioning normally.

My throat cancer is not related to HPV and has been confirmed by a lab test.

Exclusion Criteria

QTc >500 msec

I do not have any unmanaged ongoing illnesses.

My cancer has a specific genetic change known as Rb loss.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either palbociclib and cetuximab or cetuximab monotherapy

12 weeks

Weekly visits for cetuximab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 months

Treatment Details

Interventions

• Cetuximab
• Palbociclib

Trial Overview The study compares the effectiveness of combining Palbociclib with Cetuximab versus using Cetuximab alone in improving overall survival rates. Participants will be randomly assigned to one of these two treatments after showing progression on a PD-1/L1 inhibitor.

Participant Groups

Group I: Arm 1: Palbociclib + Cetuximab Experimental Treatment 2 Interventions

* Palbociclib by mouth 125 mg/daily on Days 1-21 of each 28 day cycle * Cetuximab: Initial dose 400mg/m\^2 intravenous (IV); Subsequent doses 250 mg/m\^2 IV, weekly

Group II: Arm 2: Cetuximab Active Control 1 Intervention

-Cetuximab: Initial dose 400mg/m\^2 intravenous (IV); Subsequent doses 250 mg/m\^2 IV, weekly

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

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer

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

The Joseph Sanchez Foundation

Collaborator

Trials

2

Recruited

220+

Findings from Research

In a post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

Monoclonal antibodies like cetuximab work by promoting receptor endocytosis and activating the immune system to reduce tumor growth in head and neck squamous cell carcinoma (HNSCC).

Different strategies for targeting EGFR, including tyrosine kinase inhibitors and antisense approaches, have unique mechanisms of action, which could lead to more effective treatments and better patient selection for EGFR inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. Cassell, A., Grandis, JR.[2021]

Cetuximab, an EGFR-inhibiting antibody used for treating certain cancers, is generally considered safe and well-tolerated, but this case highlights the potential for severe complications following its use, particularly in complex surgical situations.

The patient experienced a rare and fatal combination of complications after surgery, raising concerns about the safety of cetuximab in the context of surgical procedures, and emphasizing the need for careful monitoring and documentation of adverse effects in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome. Knauer, M., Haid, A., Ammann, K., et al.[2021]

In a study of 8 patients with recurrent/advanced colorectal cancer, 6 patients showed a positive response to cetuximab, a targeted therapy that binds to epidermal growth factor receptors (EGFR), indicating its efficacy even in later lines of treatment.

Patients receiving cetuximab in combination with CPT-11 had significantly better progression-free survival (7.3 months) and time to treatment failure (9.3 months) compared to those on cetuximab monotherapy (3.0 months and 4.5 months, respectively), highlighting the potential benefits of combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. Katsumoto, Y., Aritake, N., Endoh, A.[2018]

Cétuximab, a monoclonal antibody targeting EGFR, has been shown to improve overall survival in patients with locally advanced head and neck cancer when used alongside radiotherapy, and is now reimbursed in Belgium under specific conditions.

In metastatic head and neck cancer, adding cétuximab to platinum-based chemotherapy has demonstrated improved overall survival compared to chemotherapy alone, marking a significant advancement in treatment options, although it is not yet available to Belgian patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Monoclonal antibodies for the treatment of head and neck cancer]. Sautois, B., Martin, M., Demez, P., et al.[2018]

In a study involving 32 patients with advanced head and neck cancer, the addition of cetuximab to a treatment regimen of paclitaxel, carboplatin, and radiation was found to increase dermatologic toxicities, with 44% experiencing grade 3 radiation dermatitis.

Despite the increased skin toxicity, the combination treatment did not lead to higher mucosal toxicity compared to previous studies, suggesting that while cetuximab may enhance side effects, it does not worsen certain other adverse effects associated with cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a toxicity analysis. Birnbaum, A., Dipetrillo, T., Rathore, R., et al.[2015]

Cetuximab, an epidermal growth factor receptor inhibitor, shows promise in treating advanced squamous cell carcinoma of the head and neck due to the common expression of this protein in tumors.

Clinical trials indicate that cetuximab has modest effectiveness when used alongside chemotherapy or radiotherapy, suggesting it can be a valuable addition to treatment regimens for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Cetuximab in combination with radiotherapy or chemotherapy against advanced squamous cell carcinoma of the head and neck. Li, JZ., Zheng, JW., Zhang, ZY.[2019]

In a study of 39 patients with locally advanced head and neck cancer, a treatment regimen including cetuximab resulted in a 3-year progression-free survival rate of 70% and an overall survival rate of 74%, indicating strong long-term efficacy.

While the treatment caused significant acute toxicities, such as grade 3 or 4 oral mucositis in 54% of patients, the quality of life scores showed improvement over time, normalizing by one year after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction docetaxel, cisplatin, and cetuximab followed by concurrent radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with locally advanced head and neck cancer. Argiris, A., Heron, DE., Smith, RP., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Cetuximab. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome. [2021]

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

[The efficacy of cetuximab for metastatic colorectal cancer]. [2018]

6. Belgium pubmed.ncbi.nlm.nih.gov

[Monoclonal antibodies for the treatment of head and neck cancer]. [2018]

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

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a toxicity analysis. [2015]

8. China pubmed.ncbi.nlm.nih.gov

Evaluation of Cetuximab in combination with radiotherapy or chemotherapy against advanced squamous cell carcinoma of the head and neck. [2019]

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

Induction docetaxel, cisplatin, and cetuximab followed by concurrent radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with locally advanced head and neck cancer. [2022]