Atezolizumab + Bevacizumab for Advanced Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

+187 other locations

Overseen by Aarti Bhatia

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antiangiogenics, Aspirin, NSAIDs, others

Disqualifiers: Uncontrolled hypertension, Coagulopathy, Autoimmune, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II/III compares the standard therapy (chemotherapy plus cetuximab) versus adding bevacizumab to standard chemotherapy, versus combination of just bevacizumab and atezolizumab in treating patients with head and neck cancer that has spread to other places in the body (metastatic or advanced stage) or has come back after prior treatment (recurrent). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Cisplatin and carboplatin are in a class of chemotherapy medications known as platinum-containing compounds. They work by killing, stopping, or slowing the growth of cancer cells. Docetaxel is in a class of chemotherapy medications called taxanes. It stops cancer cells from growing and dividing and may kill them. The addition of bevacizumab to standard chemotherapy or combination therapy with bevacizumab and atezolizumab may be better than standard chemotherapy plus cetuximab in treating patients with recurrent/metastatic head and neck cancers.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain medications like high-dose aspirin, NSAIDs that affect platelet function, or immunosuppressive drugs. 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 Atezolizumab + Bevacizumab for Advanced Head and Neck Cancer?

Research shows that combinations of drugs like cetuximab, docetaxel, and cisplatin have been effective in treating head and neck cancer, and bevacizumab has shown early clinical activity against this type of cancer. These findings suggest that combining similar drugs could potentially be effective. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Bevacizumab safe for treating advanced head and neck cancer?

The safety of Bevacizumab (Avastin) has been evaluated in combination with other treatments for head and neck cancer, showing it can be used safely with certain drugs. However, specific safety data for the combination of Atezolizumab and Bevacizumab in this context is not provided in the available research. ^{1 2 4 6 7}

What makes the drug combination of Atezolizumab, Bevacizumab, Carboplatin, Cetuximab, Cisplatin, and Docetaxel unique for advanced head and neck cancer?

This drug combination is unique because it includes Atezolizumab, an immunotherapy drug that helps the immune system attack cancer cells, and Bevacizumab, which inhibits blood vessel growth in tumors, alongside traditional chemotherapy agents like Carboplatin, Cisplatin, and Docetaxel. This multi-faceted approach aims to enhance treatment effectiveness by targeting cancer through different mechanisms. ^{1 3 5 8 9}

Research Team

Aarti Bhatia

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

Adults with advanced or recurrent head and neck cancers who have progressed after first-line immune therapy can join. They must not have had certain prior treatments, severe allergies to trial drugs, active infections, uncontrolled illnesses, or recent major surgeries. Eligible participants need functioning organs and no history of significant bleeding issues or organ transplants.

Inclusion Criteria

Patient must not have a history of solid organ transplantation or stem-cell transplant

I am not on daily aspirin (>325 mg) or NSAIDs that affect blood clotting.

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive chemotherapy and/or monoclonal antibodies in cycles, with treatment repeating every 21 days for up to 6 cycles, followed by maintenance therapy for 2 years in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits at 30 days, then every 3 months if less than 2 years from randomization, and every 6 months if 2-5 years from randomization.

Up to 5 years

Regular follow-up visits (in-person)

Treatment Details

Interventions

• Atezolizumab (Monoclonal Antibodies)
• Bevacizumab (Anti-angiogenic Agent)
• Carboplatin (Platinum-containing Compounds)
• Cetuximab (Monoclonal Antibodies)
• Cisplatin (Platinum-containing Compounds)
• Docetaxel (Taxanes)

Trial Overview The study compares standard chemotherapy plus cetuximab against adding bevacizumab to this regimen versus a combination of bevacizumab and atezolizumab alone. It aims to determine if these investigational therapies are more effective for patients whose cancer has spread or returned after treatment.

Participant Groups

Group I: Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab) Experimental Treatment 9 Interventions

Patients receive treatment as in Arm B or C above based on results of the Phase II trial.

Group II: Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin) Experimental Treatment 9 Interventions

Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Group III: Phase II, Arm C (Bevacizumab, Atezolizumab) Experimental Treatment 7 Interventions

Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Group IV: Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab) Experimental Treatment 9 Interventions

Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Group V: Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin) Active Control 9 Interventions

Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

The TPEx regimen, which combines docetaxel, cisplatin, and cetuximab, achieved an objective response rate of 44.4% in 54 patients with recurrent or metastatic head and neck squamous cell carcinoma, indicating promising efficacy as a first-line treatment.

While the treatment was generally well-tolerated, notable adverse events included skin rash (16.6%) and non-febrile neutropenia (20.4%), with some serious complications leading to death, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Guigay, J., Fayette, J., Dillies, AF., et al.[2022]

In a phase I/II trial involving 22 patients with recurrent/metastatic head and neck cancer, the combination of docetaxel and pembrolizumab showed a 22.7% overall response rate, indicating potential efficacy in this difficult-to-treat population.

The treatment was associated with manageable side effects, with myelosuppression being the most common adverse event, while serious immune-related side effects were relatively rare, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. Fuereder, T., Minichsdorfer, C., Mittlboeck, M., et al.[2023]

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]

Induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) significantly improves patient outcomes, providing 4.1 quality-adjusted life years (QALYs) compared to 2.0 QALYs for the standard treatment (PF).

The cost-effectiveness analysis shows that TPF has a cost of £1,782 per QALY gained compared to PF, indicating that TPF is a cost-effective option for treating locally advanced squamous cell carcinoma of the head and neck in the UK.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost utility of docetaxel as induction chemotherapy followed by chemoradiation in locally advanced squamous cell carcinoma of the head and neck. Parthan, A., Posner, MR., Brammer, C., 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]

In a phase II trial involving 78 patients with advanced head and neck cancer, the combination of cetuximab and pemetrexed with radiation therapy showed a promising 2-year progression-free survival (PFS) rate of 79% without the addition of bevacizumab, which had a PFS of 75%.

Adding bevacizumab to the treatment increased the risk of hemorrhage without improving efficacy, suggesting that dual targeting of EGFR and VEGF may not provide additional benefits in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II randomized trial of radiation therapy, cetuximab, and pemetrexed with or without bevacizumab in patients with locally advanced head and neck cancer. Argiris, A., Bauman, JE., Ohr, J., et al.[2020]

In a study of 20 patients with locally advanced squamous cell carcinoma of the head and neck, the addition of nimotuzumab to standard TPF chemotherapy resulted in a median overall survival of 38 months, suggesting improved efficacy compared to standard treatment alone.

The treatment was well tolerated, with mostly mild side effects (grade 1/2 toxicities), indicating that nimotuzumab can be safely integrated into the chemotherapy regimen without significantly increasing adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of Nimotuzumab to Standard TPF Regimen in Locally Advanced Head and Neck Cancer: A Single Institutional Study. Koramati, SL., Sarathy, V., Varayathu, H., et al.[2022]

In a study of 63 patients with recurrent/metastatic squamous cell carcinoma of the head and neck, the combination of carboplatin and pemetrexed demonstrated a median progression-free survival (PFS) of 5.1 months and a median overall survival (OS) of 9.4 months, indicating its efficacy as a treatment option.

Among patients with oropharyngeal cancer, particularly those with HPV-positive disease, the treatment showed even better outcomes, with a median PFS of 7.0 months and median OS of 17.1 months, highlighting the potential for improved survival in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin-pemetrexed in treatment of patients with recurrent/metastatic cancers of the head and neck; superior outcomes in oropharyngeal primaries. Malhotra, B., Bellile, EL., Nguyen, NP., et al.[2020]

References

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

Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. [2022]

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

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. [2023]

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

Intravenous 5-Fluorouracil in Patients With Advanced Squamous Cell Carcinoma: A Retrospective Study. [2019]

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

Cost utility of docetaxel as induction chemotherapy followed by chemoradiation in locally advanced squamous cell carcinoma of the head and neck. [2018]

5. United States 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. [2019]

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

Phase II randomized trial of radiation therapy, cetuximab, and pemetrexed with or without bevacizumab in patients with locally advanced head and neck cancer. [2020]

7. Egypt pubmed.ncbi.nlm.nih.gov

Addition of Nimotuzumab to Standard TPF Regimen in Locally Advanced Head and Neck Cancer: A Single Institutional Study. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Carboplatin-pemetrexed in treatment of patients with recurrent/metastatic cancers of the head and neck; superior outcomes in oropharyngeal primaries. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. [2022]