Sorafenib + Chemotherapy for Head and Neck Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants, Anticonvulsants, Rifampin, St. John's Wort

Disqualifiers: Heart failure, Hypertension, HIV, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well sorafenib works with carboplatin and paclitaxel in treating participants with head and neck squamous cell cancer that has spread to other parts of the body or that has come back. Drugs used in chemotherapy, such as sorafenib, carboplatin, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

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 certain drugs like phenytoin, carbamazepine, phenobarbital, rifampin, or St. John's Wort. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug combination Sorafenib, Carboplatin, and Paclitaxel for head and neck cancer?

Research shows that the combination of paclitaxel and carboplatin has been effective in treating head and neck cancer, with studies indicating it can be active and well-tolerated, even in advanced cases. ^{1 2 3 4 5}

Is the combination of Sorafenib, Carboplatin, and Paclitaxel generally safe for humans?

The combination of Carboplatin and Paclitaxel has been studied in various head and neck cancers, showing tolerable safety profiles. Common side effects include blood-related issues like neutropenia (low white blood cell count), anemia (low red blood cell count), and thrombocytopenia (low platelet count), but these were generally manageable. ^{6 7 8 9 10}

What makes the drug combination of Sorafenib, Carboplatin, and Paclitaxel unique for head and neck cancer?

This drug combination is unique because it includes Sorafenib, a targeted therapy that inhibits tumor growth, alongside Carboplatin and Paclitaxel, which are chemotherapy agents known for their effectiveness in treating head and neck cancer. This combination aims to enhance treatment efficacy by combining different mechanisms of action. ^{8 11 12 13 14}

Research Team

George R. Blumenschein

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with recurrent or metastatic head and neck squamous cell cancer who haven't had systemic chemotherapy for metastatic disease, or if recurrent, have been off therapy for at least 6 months. They must be able to sign consent, have controlled blood pressure, adequate organ function, no major surgery recently, not pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

My kidney function is within the required range.

Absolute neutrophil count (ANC) >= 1,500/mm^3 within 7 days prior to start of first dose.

Hemoglobin >= 9.0 g/dL within 7 days prior to start of first dose.

Exclusion Criteria

I haven't had major surgery or a serious injury in the last 4 weeks.

Known or suspected allergy to sorafenib (BAY 43-9006) or any agent given in association with this trial.

I do not have severe heart failure or recent serious heart problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1, and sorafenib PO BID on days 2-19. Treatment repeats every 21 days for up to 6 courses.

18 weeks

Extended Treatment

Starting with course 7, participants receive sorafenib PO daily in the absence of disease progression or unacceptable toxicity.

Indefinite, based on disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

3-5 weeks

Treatment Details

Interventions

• Carboplatin
• Paclitaxel
• Sorafenib

Trial Overview The study tests the effectiveness of sorafenib in combination with carboplatin and paclitaxel chemotherapy drugs on participants with advanced head and neck cancer. It aims to see how well these drugs work together in stopping tumor growth by killing cells or preventing them from dividing and spreading.

Participant Groups

Group I: Treatment (carboplatin, paclitaxel, sorafenib) Experimental Treatment 3 Interventions

Participants receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1, and sorafenib PO BID on days 2-19. Treatment repeats every 21 days for up to 6 courses. Starting with course 7, participants receive sorafenib PO daily in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 27 patients with recurrent squamous cell carcinoma of the head and neck, the combination of paclitaxel and carboplatin showed an objective response rate of 29.6%, with a median response duration of 4.2 months.

However, the treatment was associated with significant toxicities, including high rates of neutropenia (62.9%) and other severe side effects, indicating a need for safer chemotherapy alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck. Pivot, X., Cals, L., Cupissol, D., et al.[2017]

The combination of paclitaxel, carboplatin, and external beam radiotherapy resulted in a high overall clinical response rate of 91% in 43 patients with advanced head and neck cancer, with 65% achieving a complete response.

Despite the promising efficacy, the treatment caused severe mucositis in 90% of patients, leading to hospitalization for 31%, highlighting significant toxicity concerns associated with this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy with weekly paclitaxel and carboplatin for locally advanced head and neck cancer: Long-term follow-up of a Brown University Oncology Group Phase II Study (HN-53). Chougule, PB., Akhtar, MS., Rathore, R., et al.[2015]

Weekly paclitaxel treatment in 74 patients with recurrent or metastatic head and neck cancer showed a 29% overall response rate, indicating promising efficacy in this challenging condition.

The treatment was associated with manageable side effects, with the most common severe adverse events being leukopenia and neutropenia, suggesting that while effective, careful monitoring of blood counts is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer. Tahara, M., Minami, H., Hasegawa, Y., et al.[2015]

Paclitaxel was found to be more effective than carboplatin in inducing cell death (apoptosis) and inhibiting growth of head and neck squamous cell carcinoma (HNSCC) cells, with its action linked to increased cyclin B1/CDC2 activity and prolonged mitotic arrest.

Combining paclitaxel and carboplatin, either simultaneously or sequentially, resulted in greater inhibition of cell growth compared to using either drug alone, highlighting the potential for enhanced therapeutic strategies in treating HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. Coleman, SC., Stewart, ZA., Day, TA., et al.[2019]

In a phase II study involving 24 heavily pretreated patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin resulted in an overall response rate of 39%, with 17% achieving a complete response and 22% a partial response.

The treatment was generally tolerable, although 79% of patients experienced neurotoxicity, and some had significant neutropenia, indicating that while effective, careful monitoring of side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. Stathopoulos, GP., Rigatos, S., Papakostas, P., et al.[2019]

In a phase II study involving 41 patients with recurrent or metastatic head and neck cancer, the combination of paclitaxel and carboplatin showed an overall response rate of 20%, with particularly promising results in nasopharyngeal cancer where 50% of evaluable patients achieved a complete response.

The treatment was associated with manageable acute and cumulative toxicities, with grade 3 to 4 side effects occurring in a small percentage of patients, indicating that the combination is both active and relatively safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study. Fountzilas, G., Athanassiadis, A., Samantas, E., et al.[2015]

In a study of 160 patients with advanced oropharyngeal squamous cell carcinoma treated with carboplatin, paclitaxel, and radiation over 10 years, the overall survival rates were 81.7% at 3 years and 70.7% at 5 years, indicating effective treatment outcomes.

The treatment demonstrated an acceptable side effect profile, with the most common adverse effect being acute dysphagia (75.25%), and only 11.9% of patients experiencing significant hematologic toxicities, suggesting carboplatin may be a safer alternative to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. Roskies, M., Kay-Rivest, E., Mascarella, MA., et al.[2018]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

In a phase II trial involving 30 patients with recurrent head and neck cancer, high-dose paclitaxel (250 mg/m2) demonstrated a 40% response rate, indicating its potential effectiveness as a treatment option.

The main side effects observed were neutropenia, peripheral neuropathy, and arthralgias/myalgias, which are consistent with previous studies, suggesting that while paclitaxel is promising, careful monitoring for these toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol) for the treatment of head and neck cancer. Forastiere, AA.[2015]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck. [2017]

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

Concurrent chemoradiotherapy with weekly paclitaxel and carboplatin for locally advanced head and neck cancer: Long-term follow-up of a Brown University Oncology Group Phase II Study (HN-53). [2015]

3. Germany pubmed.ncbi.nlm.nih.gov

Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer. [2015]

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Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. [2019]

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

Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. [2018]

9. Greece pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. [2023]

10. England pubmed.ncbi.nlm.nih.gov

A phase II study of combination paclitaxel and carboplatin in advanced nasopharyngeal carcinoma. [2019]

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

Paclitaxel (Taxol) for the treatment of head and neck cancer. [2015]

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Chemotherapy in head and neck cancer. Overview of newer agents. [2022]

13. China pubmed.ncbi.nlm.nih.gov

[Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer: a Meta-analysis of the efficacy and safety]. [2018]

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

Head and neck cancer: integrating anti-EGFR treatment with standard therapy. [2018]