Personalized Adaptive Therapy for Head and Neck Cancer

Overseen By Clinical Trials Intake

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must not be taking: Steroids, Immunosuppressants, others

Disqualifiers: Metastatic disease, Immunodeficiency, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for treating head and neck cancer by using a blood test to tailor treatments to individual patients. The goal is to determine if this personalized approach can effectively treat locally advanced head and neck cancers that haven't spread. Participants will receive a combination of chemotherapy drugs, including Carboplatin and Cetuximab, along with radiation, with some receiving lower doses if their cancer responds well. This trial suits those diagnosed with stage III or IV HPV-negative head and neck cancer that has not been treated with chemotherapy or radiation before. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

A previous study tested the combination of paclitaxel, carboplatin, and cetuximab in patients with head and neck cancer. The results showed that patients generally tolerated this combination well. Most side effects, such as tiredness and nausea, were expected and manageable, while serious side effects occurred less frequently.

Research has indicated that low-dose radiation therapy can also be safe for head and neck cancer. Studies have found that reducing the radiation dose does not increase the risk of cancer recurrence, suggesting that side effects might be less severe compared to standard doses.

Standard-dose radiation is commonly used and considered safe for treating head and neck cancer, though it can cause side effects like skin changes and tiredness, which are usually manageable with medical care.

In this trial, patients might receive varying radiation doses based on their response to treatment. Overall, evidence suggests that both the drug combination and radiation treatments are safe, with controllable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Personalized Adaptive Therapy for head and neck cancer because it tailors treatment based on individual responses. Unlike the standard of care, which often involves a fixed regimen of chemotherapy and radiation, this approach adapts after initial chemotherapy cycles based on how well the cancer responds. This means that patients with significant tumor shrinkage may receive lower doses of radiation, potentially reducing side effects while maintaining effectiveness. It’s a promising step towards more precise and personalized cancer care.

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

Research has shown that combining the drugs paclitaxel, carboplatin, and cetuximab effectively treats head and neck cancer. Studies indicate that this combination can slow tumor growth and relieve symptoms for many patients. It is generally well-tolerated, making it a promising option for those needing a strong initial treatment. In this trial, all participants will receive this combination during the induction treatment phase.

For radiation therapy, the trial includes two separate cohorts based on disease response. Participants with significant disease response will receive low-dose radiation, which previous studies have associated with better survival rates and fewer side effects. Meanwhile, participants with limited disease response will receive standard-dose radiation. This approach aims to tailor treatment intensity to individual patient needs, potentially reducing discomfort while maintaining effective cancer treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Ari Rosenberg, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults with locally advanced, non-metastatic head and neck squamous cell carcinoma that's HPV negative. They must have measurable disease, no prior cancer treatments or surgeries (with some exceptions), normal organ function, and agree to contraception if applicable. Excluded are those with certain infections, other cancers needing treatment, significant heart or psychiatric conditions.

Inclusion Criteria

I have not had complete surgery for head or neck cancer in the last 8 weeks.

My cancer is at stage III or IV.

My organs are functioning normally.

Exclusion Criteria

The origin of my cancer is unknown.

Intercurrent medical illnesses impairing patient tolerance to therapy or limiting survival

My cancer has spread to distant parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive 3 cycles (9 weeks) of chemotherapy with paclitaxel, carboplatin, and cetuximab

9 weeks

Response-adaptive Treatment

Participants receive either low dose or standard dose radiation treatment with additional chemotherapy based on disease response

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cetuximab
• Cisplatin
• Low Dose Radiation
• Paclitaxel
• Standard Dose Radiation
• TFHX Regimen

Trial Overview The study tests if blood biomarker testing can tailor treatment for head and neck cancer patients. It involves chemotherapy drugs like Cisplatin or Carboplatin combined with Paclitaxel and Cetuximab plus radiation therapy at standard or low doses based on the TFHX regimen.

How Is the Trial Designed?

Group I: Induction Treatment Arm Experimental Treatment 3 Interventions

All participants will receive 3 cycles (9 weeks) of chemotherapy with paclitaxel, carboplatin, and cetuximab.

Group II: De-Escalation CRT Cohort Experimental Treatment 3 Interventions

After completing induction chemotherapy, participants that have significant disease response by imaging will receive low dose radiation treatment with additional chemotherapy (CRT). Investigator will choose the appropriate chemotherapy backbone to be given during CRT.

Group III: Standard Treatment Cohort Active Control 3 Interventions

After completing induction chemotherapy, participants that have limited disease response by imaging will receive standard dose radiation treatment with additional chemotherapy (CRT). Investigator will choose the appropriate chemotherapy backbone to be given during CRT.

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

The ERBITAX regimen (paclitaxel and cetuximab) demonstrated a response rate of 37.7% in 531 patients with recurrent/metastatic squamous cell carcinoma of the head and neck who were ineligible for cisplatin-based chemotherapy, indicating its efficacy as a first-line treatment.

Patients who received immunotherapy after ERBITAX treatment had significantly improved overall survival (OS) of 29.8 months compared to 13.8 months for those receiving other treatments, suggesting a beneficial sequential treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck. Rubió-Casadevall, J., Cirauqui Cirauqui, B., Martinez Trufero, J., et al.[2023]

In a case series of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), a combination treatment of paclitaxel, carboplatin, cetuximab, and pembrolizumab resulted in significant clinical responses, with all patients achieving an objective response (6 complete responses and 2 partial responses).

The treatment was generally safe, with manageable adverse events, although one patient experienced liver toxicity related to the immune checkpoint inhibitor. This suggests that the quadruple therapy could be a promising option for R/M HNSCC, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Response Rate to Carboplatin-Paclitaxel-Cetuximab and Pembrolizumab in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Chauffert, B., Zhou, Y., Medjkoune, L., et al.[2023]

Patients with locally advanced oropharyngeal squamous cell carcinoma who received cisplatin (CDDP) had a significantly better 2-year overall survival rate compared to those treated with cetuximab (CTX), with a hazard ratio of 1.68 indicating higher mortality for CTX users.

Cisplatin also resulted in lower overall treatment costs compared to CTX and carboplatin, despite higher rates of antiemetic use and hospital visits for side effects, suggesting it may be a more cost-effective option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma. Amini, A., Eguchi, M., Jones, BL., et al.[2023]

In a phase I study involving 25 patients with advanced head and neck squamous cell carcinoma (HNSCC), the maximum tolerated dose of nab-paclitaxel was determined to be 60 mg/m² when combined with cetuximab and intensity-modulated radiation therapy (IMRT).

The treatment regimen showed promising outcomes, with a 2-year failure-free survival rate of 65% and an overall survival rate of 91%, suggesting that nab-paclitaxel could be a viable nonplatinum alternative to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC). Fury, MG., Sherman, EJ., Rao, SS., et al.[2023]

In a subgroup analysis of 33 patients with HPV-related oropharyngeal cancer, treatment with cisplatin (CDDP) showed a trend towards better locoregional control and overall survival compared to cetuximab (CTX), suggesting that CDDP may be a more effective first-line treatment for these patients.

Serious or fatal infectious complications were only observed in the CTX treatment group, indicating potential safety concerns associated with cetuximab in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup Analysis According to Human Papillomavirus Status and Tumor Site of a Randomized Phase II Trial Comparing Cetuximab and Cisplatin Combined With Radiation Therapy for Locally Advanced Head and Neck Cancer. Buglione, M., Maddalo, M., Corvò, R., et al.[2018]

In a study of 180 patients with head and neck cancer, those treated with cetuximab experienced significantly higher rates of acute dermal toxicity (34.5%) compared to those who did not receive cetuximab (10.3%).

Despite the increased skin toxicity, there were no significant differences in local control or overall survival between patients treated with cetuximab and those treated without it, indicating that cetuximab does not improve survival outcomes when combined with IMRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer. Bibault, JE., Morelle, M., Perrier, L., et al.[2022]

In a phase II trial involving 30 patients with locally advanced head and neck squamous cell carcinoma (HNSCC), the treatment regimen of nab-paclitaxel, cisplatin, and 5-FU followed by concurrent radiation therapy showed high efficacy, with a two-year disease-specific survival (DSS) rate of 94% for HPV-related cases and 100% for HPV-unrelated cases.

The trial reported a low relapse rate of only 3%, indicating that this treatment approach is effective and safe for patients with advanced HNSCC, with most patients remaining free of disease progression after two years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel, cisplatin, and 5-fluorouracil followed by concurrent cisplatin and radiation for head and neck squamous cell carcinoma. Adkins, D., Ley, J., Michel, L., et al.[2022]

Citations

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Radiation therapy in head and neck cancer - PMC Modern radiotherapy techniques resulted in the improvement of cancer control. Several types of management of toxicity-induced radiotherapy were implemented to ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655524005430

Outcomes With Radiation Therapy as Primary Treatment ... Radiation therapy can effectively treat unresectable head and neck cutaneous SCC. It has a high response rate, with higher doses producing longer disease ...

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Elective Radiotherapy Dose and Field in HPV-Associated ... This cohort study found that the evaluated de-escalation strategy for elective regions showed favorable clinical outcomes and QOL profiles.

4. targetedonc.com targetedonc.com/view/reduced-dose-rt-safe-effective-for-head-neck-cancer-lowering-toxicity

Reduced-Dose RT Safe & Effective for Head & Neck ... Overall survival (OS) was improved in the reduced-dose group vs control group, with a median OS of 83.3 months (95% CI; 78.1-88.7; P =.483) and ...

5. mdpi.com mdpi.com/2072-6694/13/19/4912

An Updated Review on Head and Neck Cancer Treatment ... Overall survival (OS) rates for 5- and 10-year marks were found to be 32% and 20%, respectively. The study has found that increasing the dose from 57.5 to 68.4 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7533405/

Late side effects of radiation treatment for head and neck cancer RT can damage blood vessels that nourish muscles, nerves, and bones resulting in a progressive “radiation fibrosis syndrome”, which causes a variety of ...

7. dailynews.ascopubs.org dailynews.ascopubs.org/do/reduced-elective-dose-safe-definitive-radiotherapy-head-and-neck-cancer

Reduced Elective Dose is Safe in Definitive Radiotherapy ... The most important finding was that the reduced elective radiation dose was safe with uncompromised recurrence and survival rates.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0167814025052004

Dose de-escalation of elective neck irradiation in head and ... Reduced elective dose resulted in significantly more patients with a pharyngeal mucosal epithelium mean dose below 45 Gy. This was associated ...

9. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/analysis-clarifies-risk-of-second-malignancies-with-radiation-therapy-for-hpv-positive-head-and-neck-cancers

Second Malignancy Risk with RT for HPV+ Head & Neck ... Analysis Clarifies Risk of Second Malignancies with Radiation Therapy for HPV-Positive Head and Neck Cancers ... Low-Dose Radiation Therapy.

10. redjournal.org redjournal.org/article/S0360-3016(20)34540-5/fulltext

Reduced Dose and Volume Elective Nodal Radiation ... Head and neck cancer radiation therapy side effects are dose-dependent, and advanced radiation delivery is highly conformal, such that target dose and volume ...