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

Trial Summary

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.

What data supports the effectiveness of the treatment for head and neck cancer?

Research shows that combining cetuximab with intensity-modulated radiation therapy (IMRT) is more effective than using radiation alone for head and neck cancer. Additionally, a combination of carboplatin, paclitaxel, cetuximab, and pembrolizumab has shown high response rates in patients with recurrent or metastatic head and neck cancer, indicating potential effectiveness. ^{1 2 3 4 5}

Is the Personalized Adaptive Therapy for Head and Neck Cancer safe for humans?

The combination of cetuximab, paclitaxel, and carboplatin has been used in patients with head and neck cancer, and while some adverse events were noted, they were generally manageable. A study involving cetuximab and intensity-modulated radiation therapy (IMRT) also reported manageable toxicity, suggesting that these treatments are generally safe for humans. ^{1 2 3 6 7}

What makes the treatment for head and neck cancer unique?

This treatment is unique because it combines personalized adaptive therapy with a mix of drugs and radiation, including carboplatin, cetuximab, and paclitaxel, which have shown effectiveness in enhancing radiation therapy outcomes and managing advanced head and neck cancer. ^{1 2 3 4 7}

What is the purpose of this trial?

This clinical trial will assess whether or not blood based biomarker testing can be used to personalize cancer treatment for patients with locally advanced head and neck cancer.

Research Team

Ari Rosenberg, MD

Principal Investigator

University of Chicago

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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]

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]

References

1. England 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). [2023]

2. France pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer. [2022]

3. Switzerland 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel, cisplatin, and 5-fluorouracil followed by concurrent cisplatin and radiation for head and neck squamous cell carcinoma. [2022]

5. United States 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. [2018]

6. Switzerland 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. [2023]

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

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma. [2023]