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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—sorafenib (Nexavar), carboplatin, and paclitaxel—to evaluate their effectiveness against head and neck squamous cell cancer that has returned or spread. These drugs aim to halt cancer growth by killing cancer cells or preventing them from dividing or spreading. Participants with head and neck cancer that has spread or recurred after treatment, and who have not received prior chemotherapy for metastatic disease, may be suitable for this trial. As a Phase 2 trial, this 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 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.

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

Research has shown that the combination of carboplatin, paclitaxel, and sorafenib has been tested in patients with various cancers. Previous studies with carboplatin and paclitaxel found these drugs to be generally well-tolerated and safe for many, though some might experience side effects like nausea or hair loss.

Sorafenib, when added, has been used safely in other conditions for many patients. Some might experience side effects such as fatigue or changes in blood pressure. In studies where these drugs were used together, the combination was deemed safe enough for further exploration.

This trial is in its early stages, so researchers are still learning about how well people can handle these drugs together. It's important to discuss any concerns with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for head and neck cancer, which typically involve chemotherapy and radiation, this experimental approach combines traditional chemotherapy agents, carboplatin and paclitaxel, with sorafenib, a targeted therapy. Sorafenib is unique because it works by inhibiting specific proteins that promote cancer cell growth, offering a different mechanism of action compared to standard chemotherapy. Researchers are excited about this combination because it has the potential to enhance treatment effectiveness and delay disease progression more effectively than existing options.

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

Research has shown that sorafenib, which participants in this trial will receive, can help control tumors in head and neck cancer by facilitating the inactivation of cancer cells. Previous studies indicate that it is usually well tolerated, with few serious side effects. Participants in this trial will also receive a combination of carboplatin and paclitaxel. In earlier studies, this combination resulted in tumor shrinkage in about 4 out of 10 patients. These drugs work together by killing cancer cells and preventing their spread. This combination shows promise for treating head and neck cancer that is difficult to manage or has recurred. ^{2 6 7 8 9}

Who Is on the Research Team?

George R. Blumenschein

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9470832/

Effectiveness of paclitaxel and carboplatin combination in ... Four patients (17%) achieved a complete response and 5 (22%) a partial response for an overall response rate of 39%. Duration of response was 3-9 months.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00176267

Paclitaxel, Carboplatin And Low Dose Radiation As ... This study is being performed utilizing two cycles of Paclitaxel and Carboplatin, plus low doses radiation as initial therapy prior to other treatment (surgery ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)41203-9/fulltext

Long-term outcomes with concurrent carboplatin, paclitaxel ... Treatment with concurrent carboplatin, paclitaxel and radiation is safe and offers curative potential for poor prognosis patients with locally advanced SCCHN.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.6042

Efficacy and toxicity of weekly paclitaxel, carboplatin, and ... 53 patients (66%) experienced at least one dose interruption due to adverse effects. 11 patients (14%) stopped treatment due to toxicities. 58 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17675395/

Long-term outcomes with concurrent carboplatin, paclitaxel ... With a median follow-up of 69 months for surviving patients, the 5-year progression-free survival was 36% and the 5-year overall survival was 35%. Two of the 18 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00494182?cond=%22Laryngeal%20Squamous%20Cell%20Carcinoma%22&intr=%22Carboplatin%22&viewType=Table&rank=1

Sorafenib in Combination With Carboplatin and Paclitaxel ... A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/14/15/4836/72639/A-Phase-I-Trial-of-the-Oral-Multikinase-Inhibitor

A Phase I Trial of the Oral, Multikinase Inhibitor Sorafenib in ... In a retrospective analysis, 26% of patients with advanced melanoma treated with a carboplatin-paclitaxel combination had partial response (23).

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8582411/

Current and Emerging Molecular Therapies for Head ... This paper outlines current and emerging molecular therapies for head and neck cancer, and updates readers on outcomes of the most pertinent clinical trials in ...

9. trial.medpath.com trial.medpath.com/clinical-trial/a00ae5620e2d07e0/sorafenib-carboplatin-paclitaxel-metastatic-head-neck-cancer

Sorafenib in Combination With Carboplatin and Paclitaxel in ... This phase II trial studies how well sorafenib works with carboplatin and paclitaxel in treating participants with head and neck squamous cell cancer that ...