Chemotherapy + Bevacizumab for Head and Neck Cancers

Recruiting at 878 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Bevacizumab, Anticoagulants, NSAIDs, others

Disqualifiers: Brain metastases, Bleeding history, 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: 24

Duration: Varies, typically 21-day cycles

403 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This randomized phase III trial studies chemotherapy to see how well it works with or without bevacizumab in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or that has spread to other parts of the body (metastatic). Drugs used in chemotherapy, such as docetaxel, cisplatin, carboplatin, and fluorouracil, 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. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also make tumor cells more sensitive to chemotherapy and stop the growth of head and neck cancer by blocking blood flow to the tumor. It is not yet known whether combination chemotherapy is more effective when given with or without bevacizumab in treating patients with head and neck squamous cell carcinoma.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on any other investigational agents, and certain medications like high-dose aspirin or NSAIDs that affect platelet function are restricted. It's best to discuss your current medications with the trial team to ensure they don't interfere with the study.

Is the combination of chemotherapy drugs including docetaxel, cisplatin, and 5-fluorouracil safe for head and neck cancer patients?

Studies have shown that the combination of docetaxel, cisplatin, and 5-fluorouracil is generally safe for patients with head and neck cancer, although it can cause side effects. These side effects may include nausea, fatigue, and low blood cell counts, which are common with chemotherapy treatments. ^{1 2 3 4 5}

What makes the chemotherapy and bevacizumab drug combination unique for head and neck cancers?

This treatment combines chemotherapy drugs with bevacizumab, which targets blood vessel growth in tumors, potentially enhancing the effectiveness of chemotherapy. The combination of docetaxel, cisplatin, and 5-fluorouracil is known for high response rates, and adding bevacizumab may improve outcomes by inhibiting tumor blood supply. ^{2 6 7 8 9}

What data supports the effectiveness of the drug combination used in the clinical trial for head and neck cancers?

Research shows that the combination of docetaxel, cisplatin, and 5-fluorouracil (TPF) has been effective in treating head and neck cancers, with response rates ranging from 52% to 100% in some studies. Additionally, docetaxel combined with cisplatin has shown response rates of 33% to 44% in recurrent disease, with promising survival outcomes. ^{2 10 11 12 13}

Who Is on the Research Team?

Athanassios (Ethan) Argiris

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with recurrent or metastatic head and neck squamous cell carcinoma who haven't had chemotherapy or targeted therapy for the recurrence. They must have adequate blood counts, organ function, no severe bleeding history, controlled blood pressure without major surgery recently, and no brain metastases. Pregnant women are excluded.

Inclusion Criteria

Patients must not be receiving any other investigational agent while on the study

My cancer can be measured by scans.

Patients must meet specified laboratory values for ANC, Hgb, platelet count, creatinine clearance, total bilirubin, AST or ALT, alkaline phosphatase, and urine dipstick

Exclusion Criteria

My cancer has not caused major bleeding or required blood-thinning medication.

I have no severe allergies to docetaxel or polysorbate 80.

Women must not be pregnant or breastfeeding; agreement to use adequate birth control is required for women of child-bearing potential and men

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy with or without bevacizumab. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Varies, typically 21-day cycles

Visits every 21 days for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3 months for 2 years, then every 6 months for 3 years.

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• Cisplatin
• Docetaxel
• Fluorouracil

Trial Overview The study compares the effectiveness of standard chemotherapy drugs (docetaxel, cisplatin, carboplatin, fluorouracil) alone versus combined with bevacizumab (a drug that may block tumor blood supply). It's a phase III trial to see if adding bevacizumab improves treatment outcomes.

How Is the Trial Designed?

Group I: Arm IVB (carboplatin, fluorouracil, bevacizumab) Experimental Treatment 4 Interventions

Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.

Group II: Arm IIIB (cisplatin, fluorouracil, bevacizumab) Experimental Treatment 4 Interventions

Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA.

Group III: Arm IIB (docetaxel, carboplatin, bevacizumab) Experimental Treatment 4 Interventions

Patients receive bevacizumab as in Arm IB and docetaxel and carboplatin as in Arm IIA.

Group IV: Arm IB (docetaxel, cisplatin, bevacizumab) Experimental Treatment 4 Interventions

Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA.

Group V: Arm IIIA (cisplatin, fluorouracil) Active Control 3 Interventions

Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group VI: Arm IVA (carboplatin, fluorouracil) Active Control 3 Interventions

Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group VII: Arm IIA (docetaxel, carboplatin) Active Control 3 Interventions

Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group VIII: Arm IA (docetaxel, cisplatin) Active Control 3 Interventions

Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days 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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of docetaxel and cisplatin demonstrated a significant overall response rate of 53.7% in patients with locally advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, indicating its efficacy as a treatment option.

Despite common hematologic and non-hematologic toxicities, the treatment was generally well-tolerated, with serious adverse effects being infrequent due to the use of corticosteroid prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. Schöffski, P., Catimel, G., Planting, AS., et al.[2020]

Docetaxel shows promising efficacy as a treatment for recurrent squamous cell cancer of the head and neck, with response rates between 33% to 44% when combined with cisplatin, and median survival times of 9.6 to 11 months.

In the neoadjuvant setting, docetaxel has demonstrated response rates greater than 90%, indicating its potential for improving disease-free and overall survival, with ongoing trials comparing its effectiveness to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. Glisson, BS.[2018]

The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) showed a response rate of 64% in patients at dose level I and 78.3% at dose level II, indicating significant efficacy in treating squamous cell carcinoma of the head and neck (SCCHN).

The treatment was associated with manageable safety concerns, with dose-limiting toxicities including renal toxicity and nausea, and the maximum tolerated dose was reached at level II, suggesting that dose level I is safer and recommended for further testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study. Schrijvers, D., Van Herpen, C., Kerger, J., et al.[2020]

In a study of 143 patients with Stage III-IV head and neck squamous cell carcinoma, carboplatin-paclitaxel (CT) induction chemotherapy resulted in significantly better locoregional control (80.5%) and progression-free survival (73.2%) compared to docetaxel-cisplatin-5-fluorouracil (TPF) chemotherapy (55.5% and 60.7%, respectively).

TPF was associated with worse renal toxicity and a higher rate of chemotherapy dose reductions during treatment, suggesting that CT may be a safer and more effective option for patients undergoing induction chemotherapy before chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer. Herman, LC., Chen, L., Garnett, A., et al.[2021]

In a study of 38 patients with locally advanced head and neck squamous cell carcinoma, the combination of docetaxel and carboplatin with radiotherapy resulted in a clinical response in 74.3% of patients, indicating effective treatment.

The regimen was generally well tolerated, with no Grade 4 toxicities reported, although common Grade 3 side effects included mucositis, xerostomia, and dysphagia, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of docetaxel and carboplatin with concurrent radiation therapy for locally advanced head and neck cancer. Chitapanarux, I., Lorvidhaya, V., Tharavichitkul, E., et al.[2018]

In a phase II study involving 31 patients with advanced squamous cell carcinoma of the head and neck, docetaxel demonstrated significant activity, with a major response rate of 42% and a median response duration of 5 months.

Docetaxel was well tolerated, with manageable side effects such as leukopenia and fatigue, and the use of premedication helped reduce the incidence of severe toxicities, allowing for safe outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: an active drug for squamous cell carcinoma of the head and neck. Dreyfuss, AI., Clark, JR., Norris, CM., et al.[2018]

In a phase I trial involving 13 patients with advanced head and neck cancer, the maximum tolerated dose of erlotinib was determined to be 50 mg daily, as higher doses led to significant gastrointestinal toxicities, including bleeding and perforation.

Despite the treatment's activity, with 38% of patients showing no evidence of disease after a median follow-up of 23.4 months, the high rates of toxicity and study withdrawals indicate that this combination therapy is not suitable for advancement to phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer. Ahn, PH., Machtay, M., Anne, PR., et al.[2019]

Docetaxel, when used in combination with platinum and 5-fluorouracil (5FU) as part of the TPF regimen, shows a high overall response rate of 85 to 90% in treating head and neck carcinoma, with manageable acute toxicity.

Docetaxel acts as a radiosensitizer, making it a feasible option for concurrent radiochemotherapy, but further trials are needed to determine the best combination regimen with radiation and other chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Docetaxel and squamous cell carcinoma of the head and neck]. Calais, G.[2018]

The combination of carboplatin, oral tegafur, and cetuximab is a safe and well-tolerated first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), with a high compliance rate among patients.

In a study of 104 patients, the treatment resulted in a median overall survival of 11 months and a progression-free survival of 6 months, with an overall response rate of 35%, indicating its efficacy in managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous 5-Fluorouracil in Patients With Advanced Squamous Cell Carcinoma: A Retrospective Study. Buxó, E., Sosa, A., Reig, O., et al.[2019]

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Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. [2020]

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The role of docetaxel in the management of squamous cell cancer of the head and neck. [2018]

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Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study. [2020]

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Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A phase II study of docetaxel and carboplatin with concurrent radiation therapy for locally advanced head and neck cancer. [2018]

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Docetaxel: an active drug for squamous cell carcinoma of the head and neck. [2018]

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Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer. [2019]

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