Atezolizumab + Bevacizumab for Advanced Head and Neck Cancer

Not currently recruiting at 197 trial locations

Overseen By Minh Phan

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: National Cancer Institute (NCI)

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

Disqualifiers: Uncontrolled hypertension, Coagulopathy, Autoimmune, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to find a better treatment for advanced or recurring head and neck cancer. It compares standard chemotherapy with a combination of new drugs, including bevacizumab (an antiangiogenic drug) and atezolizumab (an immunotherapy drug), which may help the immune system fight cancer and inhibit tumor growth. Several treatment groups will test different combinations of these drugs. Individuals with advanced head and neck cancer that has spread or recurred after treatment may be suitable candidates, particularly if they have previously received immune therapy but not antiangiogenic treatments like bevacizumab. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in cancer therapy.

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.

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

Research has shown that combining atezolizumab and bevacizumab has been studied in people with advanced cancers. These studies suggest that managing this combination is generally safe. Some serious side effects have been reported, but they are uncommon.

Other research has shown that combining docetaxel, cisplatin or carboplatin, and bevacizumab yields promising results for treating head and neck cancer. Adding bevacizumab to this mix has been linked to longer survival in some cases. However, like many cancer treatments, side effects can occur and may vary from person to person.

These treatments are in the later stages of clinical trials, indicating some evidence of their safety in humans. However, more information is needed to fully understand all potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab and bevacizumab for advanced head and neck cancer because it offers a novel approach compared to standard treatments like cisplatin or cetuximab. Unlike most treatments that focus solely on attacking cancer cells, atezolizumab is an immunotherapy drug that boosts the body's immune system to better identify and fight cancer cells. Bevacizumab, on the other hand, is an anti-angiogenic drug that cuts off the blood supply tumors need to grow. This dual approach not only targets the cancer cells directly but also disrupts their support systems, potentially leading to more effective and longer-lasting outcomes for patients.

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

Research has shown that using atezolizumab and bevacizumab together, as tested in one arm of this trial, may help treat advanced cancers. Specifically, some studies found that 36% of patients with advanced tumors experienced tumor shrinkage or disappearance with this treatment. Atezolizumab, a type of immunotherapy, helps the body's immune system fight cancer, while bevacizumab cuts off the blood supply tumors need to grow. Another treatment combination being tested in this trial—docetaxel, cisplatin or carboplatin, and bevacizumab—has proven effective and manageable for head and neck cancers. This combination has also shown good results in other advanced cancers, suggesting potential benefits for head and neck cancer as well. ^{1 2 3 6 7}

Who Is on the Research Team?

Aarti Bhatia

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Carboplatin
• Cetuximab
• Cisplatin
• Docetaxel

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.

How Is the Trial Designed?

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 IV 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.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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

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]

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]

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]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

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. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

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 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]

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]

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]

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]

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