Vaccine + Chemotherapy for Head and Neck Cancer

Overseen by Ari Rosenberg, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Chicago

Must not be taking: Immunosuppressants, Herbal remedies

Disqualifiers: Metastatic disease, Autoimmune disorders, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Doctors leading this study hope to learn about the safety and effectiveness of combining medications HB-201 and HB-202 (also known as TheraT® vectors) with chemotherapy using carboplatin and paclitaxel in the beginning of the study (induction) and if combining these medications can increase tumor shrinkage after therapy and reduce the amount of radiotherapy and chemotherapy that will later be needed. In addition, the study is looking at ways to reduce side effects overall using robotic surgery, chemotherapy and radiotherapy, or radiotherapy alone. Your participation in this research will last about 2 years. HB-201 and HB-202 are experimental (meaning the US Food and Drug Administration (FDA) has not approved these drugs), and therefore they can only be given in a research study.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take chronic immunosuppressive medications or herbal remedies with immune-stimulating properties within 28 days before starting the study treatment.

What data supports the effectiveness of the drug combination of paclitaxel and carboplatin for head and neck cancer?

Research shows that the combination of paclitaxel and carboplatin has significant activity in treating recurrent or metastatic head and neck cancer, with some patients achieving complete or partial responses. Additionally, this combination allows for outpatient treatment, which can improve patients' quality of life. ^{1 2 3 4 5}

Is the combination of paclitaxel and carboplatin safe for treating head and neck cancer?

The combination of paclitaxel and carboplatin has been studied in patients with head and neck cancer, showing manageable side effects. Common side effects include neutropenia (low white blood cell count), neurotoxicity (nerve damage), and myelosuppression (reduced bone marrow activity), but these were generally tolerable and did not lead to treatment discontinuation. ^{3 6 7 8 9}

What makes the Vaccine + Chemotherapy treatment for head and neck cancer unique?

This treatment combines a vaccine (HB-201, HB-202) with chemotherapy drugs (Carboplatin and Paclitaxel), which is a novel approach as it integrates immunotherapy with traditional chemotherapy to potentially enhance the body's immune response against cancer cells while also targeting them with chemotherapy. ^{1 2 10 11 12}

Research Team

Ari Rosenberg, MD

Principal Investigator

University of Chicago - Comprehensive Cancer Center

Eligibility Criteria

Adults with HPV16-positive head and neck cancers, specifically oropharyngeal carcinoma, who haven't had prior radiation/chemotherapy or complete surgical resection recently. They must have a certain level of tumor size/spread, be in good health with normal organ function, not pregnant/breastfeeding, and willing to use contraception.

Inclusion Criteria

Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment.

My cancer is caused by the HPV16 virus.

Women must not be breastfeeding.

Exclusion Criteria

I have another cancer, but it's not getting worse or needing treatment, except for certain skin cancers or early cervical cancer.

I haven't taken long-term immune-weakening drugs in the last 6 months.

I do not have any severe illnesses that my treatment would worsen.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive HB-201 and HB-202 (TheraT® vectors) combined with chemotherapy using carboplatin and paclitaxel

9 weeks

3 cycles of 21 days each

Surgery/Radiotherapy

Participants undergo surgery, radiotherapy alone, or chemotherapy with radiotherapy based on tumor response

Varies based on treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• HB-201 (Cancer Vaccine)
• HB-202 (Cancer Vaccine)
• Paclitaxel (Chemotherapy)
• Transoral Robotic Surgery (Procedure)

Trial Overview The trial tests the safety and effectiveness of TheraT® vectors (HB-201 and HB-202) combined with chemotherapy drugs carboplatin and paclitaxel. It aims to see if this combination can shrink tumors more effectively than standard treatments alone.

Participant Groups

Group I: Phase 2: Efficacy Arm 2 - HB-201 and HB-202 + Chemotherapy Experimental Treatment 5 Interventions

Participants in this group will receive alternating doses of HB-201 and HB-202 combined with chemotherapy using carboplatin and paclitaxel at the dose established in the first phase of the study. After completing treatment at the established phase 2 dose, subjects will receive surgery, radiotherapy alone, or chemotherapy with radiotherapy together based on how their tumor responds to the medications.

Group II: Phase 2: Efficacy Arm 1 - HB-201 + Chemotherapy Experimental Treatment 5 Interventions

Participants in this group will receive HB-201 combined with chemotherapy using carboplatin and paclitaxel at the dose established in the first phase of the study. After completing treatment at the established phase 2 dose, subjects will receive surgery, radiotherapy alone, or chemotherapy with radiotherapy together based on how their tumor responds to the medications.

Group III: Phase 1: Dose-Finding Group 2 - Drug Combination 2 Experimental Treatment 4 Interventions

All participants in this group will receive alternating doses of HB-201 and HB-202 combined with chemotherapy using carboplatin and paclitaxel. Participants will be given 3 doses of HB-201 \& HB-202 alternating two vector therapy. Patients will receive 2 doses of HB-202 and 1 dose of HB-201. HB-202 will be administered on cycle 1 day 15 and cycle 3 day 15, and HB-201 will be administered on cycle 2 day 15 with three 21-day cycles of chemotherapy with carboplatin on day 1 and paclitaxel 100mg/m2 on days 1, 8, and 15.

Group IV: Phase 1: Dose-Finding Group 1 - Drug Combination 1 Experimental Treatment 4 Interventions

All participants in this group will receive HB-201 combined with chemotherapy using carboplatin and paclitaxel. - HB-201 will be administered on cycle 1 day 15, cycle 2 day 15, and cycle 3 day 15 with three 21-day cycles of carboplatin on day 1 and paclitaxel 100mg/m2 on days 1, 8, and 15

Carboplatin is already approved in Canada for the following indications:

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+

Pete Salzmann

University of Chicago

Chief Executive Officer since 2018

MD from University of Chicago’s Pritzker School of Medicine, MBA from Stanford University’s Graduate School of Business

Anh Nguyen

University of Chicago

Chief Medical Officer

MD from Rutgers New Jersey Medical School, MBA from University of Chicago

Findings from Research

In a study of 49 patients with recurrent or metastatic head and neck cancer, the combination of paclitaxel and carboplatin showed a 57% overall response rate in patients with nasopharyngeal cancer, indicating significant efficacy for this specific type of cancer.

The treatment was generally well tolerated, with only low rates of severe toxicities, suggesting it can be safely administered as an outpatient therapy, although its effectiveness was only moderate in non-nasopharyngeal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel by three-hour infusion and carboplatin in advanced carcinoma of nasopharynx and other sites of the head and neck. A phase II study conducted by the Hellenic Cooperative Oncology Group. Fountzilas, G., Skarlos, D., Athanassiades, A., et al.[2022]

Higher T and N stages in head and neck cancer are associated with lower rates of complete local control and survival, highlighting the need for improved treatment strategies.

Combined-modality treatments, such as induction chemotherapy followed by radiotherapy, show promise in enhancing survival and preserving organ function compared to aggressive surgery or radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modalities in the treatment of head and neck cancers. Aisner, J., Hiponia, D., Conley, B., et al.[2015]

In a phase I trial involving 33 patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin demonstrated a 54% overall response rate, with 27% achieving complete responses, indicating significant efficacy in treating this patient population.

The maximum tolerated dose of paclitaxel was determined to be between 230 and 265 mg/m2, with manageable side effects, primarily grade 3/4 neutropenia and thrombocytopenia, suggesting that this treatment can be safely administered while potentially enhancing organ preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in head and neck cancer. Dunphy, F., Boyd, J., Dunleavy, T.[2015]

The combination of paclitaxel, carboplatin, and external beam radiotherapy resulted in a high overall clinical response rate of 91% in 43 patients with advanced head and neck cancer, with 65% achieving a complete response.

Despite the promising efficacy, the treatment caused severe mucositis in 90% of patients, leading to hospitalization for 31%, highlighting significant toxicity concerns associated with this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy with weekly paclitaxel and carboplatin for locally advanced head and neck cancer: Long-term follow-up of a Brown University Oncology Group Phase II Study (HN-53). Chougule, PB., Akhtar, MS., Rathore, R., et al.[2015]

In a phase II study involving 49 patients with recurrent or metastatic head and neck cancer, the combination of paclitaxel and carboplatin resulted in a complete response in 8% of patients and a partial response in 24%, indicating some efficacy as a first-line treatment.

The treatment was associated with manageable toxicities, with serious side effects occurring in a small percentage of patients, and the median survival was 13.3 months, suggesting that this combination therapy can be a viable option for patients with advanced head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel in combination with carboplatin or gemcitabine for the treatment of advanced head and neck cancer. Fountzilas, G., Athanassiades, A., Kalogera-Fountzila, A., et al.[2022]

In a phase II study involving 24 heavily pretreated patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin resulted in an overall response rate of 39%, with 17% achieving a complete response and 22% a partial response.

The treatment was generally tolerable, although 79% of patients experienced neurotoxicity, and some had significant neutropenia, indicating that while effective, careful monitoring of side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. Stathopoulos, GP., Rigatos, S., Papakostas, P., et al.[2019]

Combined chemoradiotherapy using paclitaxel and carboplatin during radiotherapy for stage III and IV squamous cell carcinoma of the head and neck shows promising efficacy, with 2 out of 11 assessable patients achieving a complete response and 6 achieving a partial response.

The treatment has manageable toxicity, with no toxic deaths reported and only 10 patients requiring dose reductions, indicating that this combination therapy can be safely administered alongside radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot trial of paclitaxel, carboplatin, and concurrent radiotherapy for unresectable squamous cell carcinoma of the head and neck. Conley, B., Jacobs, M., Suntharalingam, M., et al.[2015]

In a phase I trial involving previously treated and untreated patients with advanced cancers, the maximum tolerated dose (MTD) of paclitaxel was established at 135 mg/m2 without cytokine support, with ongoing evaluations of higher doses up to 250 mg/m2 when granulocyte colony-stimulating factor is used.

Objective responses to the treatment were observed in patients with squamous cell carcinoma of the head and neck and non-small cell lung cancer, although myelosuppression was identified as the main dose-limiting toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel and carboplatin: implications for trials in head and neck cancer. Creaven, P., Raghavan, D., Pendyala, L., et al.[2015]

The combination of paclitaxel and cisplatin shows promise as an effective treatment for recurrent or metastatic squamous cell carcinoma of the head and neck, with three patients achieving partial remission in a phase I trial involving 21 participants.

The treatment regimen was associated with dose-limiting toxicities, primarily myelosuppression and orthostatic hypotension, indicating the need for careful monitoring and management of side effects as clinical trials progress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical phase I study of paclitaxel followed by cisplatin in advanced head and neck squamous cell carcinoma. Hanauske, AR., Schilling, T., Heinrich, B., et al.[2015]

In a study of 1,149 patients with advanced head and neck squamous cell carcinoma, carboplatin-based chemoradiotherapy showed similar cancer-specific mortality rates compared to cisplatin-based therapy, indicating that carboplatin can be an effective alternative for patients unable to receive cisplatin.

Both carboplatin and cisplatin-based chemoradiotherapy were found to be more effective than radiation therapy alone or radiation with cetuximab, suggesting that carboplatin should be further investigated as a viable treatment option for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer. Xiang, M., Colevas, AD., Holsinger, FC., et al.[2020]

In a study of 84 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx, concurrent treatment with carboplatin and paclitaxel alongside radiotherapy showed a 2-year overall survival rate of 46.3% and a progression-free survival rate of 41.0%.

The treatment was associated with significant acute toxicity, with 51.2% of patients experiencing severe mucositis and 6% experiencing severe leucopenia and thrombopenia, indicating that while the treatment is effective, it can also lead to considerable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel : a phase II study. Semrau, R., Temming, S., Preuss, SF., et al.[2021]

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

Paclitaxel by three-hour infusion and carboplatin in advanced carcinoma of nasopharynx and other sites of the head and neck. A phase II study conducted by the Hellenic Cooperative Oncology Group. [2022]

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

Combined modalities in the treatment of head and neck cancers. [2015]

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

Paclitaxel and carboplatin in head and neck cancer. [2015]

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

Concurrent chemoradiotherapy with weekly paclitaxel and carboplatin for locally advanced head and neck cancer: Long-term follow-up of a Brown University Oncology Group Phase II Study (HN-53). [2015]

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

Paclitaxel in combination with carboplatin or gemcitabine for the treatment of advanced head and neck cancer. [2022]

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

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. [2019]

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

A pilot trial of paclitaxel, carboplatin, and concurrent radiotherapy for unresectable squamous cell carcinoma of the head and neck. [2015]

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

Phase I study of paclitaxel and carboplatin: implications for trials in head and neck cancer. [2015]

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

Clinical phase I study of paclitaxel followed by cisplatin in advanced head and neck squamous cell carcinoma. [2015]

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

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel : a phase II study. [2021]

12. 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]