Vaccine + Chemotherapy for Head and Neck Cancer

Overseen By Clinical Trials Email

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Chicago

Must not be taking: Immunosuppressants, Herbal remedies

Disqualifiers: Metastatic disease, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: 3

98 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining two experimental vaccines, HB-201 and HB-202, with chemotherapy drugs carboplatin (Paraplatin) and paclitaxel (Taxol) can more effectively shrink head and neck tumors. Researchers aim for this combination to reduce the need for more intense treatments like radiotherapy and surgery later. The trial also explores ways to lessen treatment side effects. Suitable candidates have HPV16-positive head and neck cancer and have not yet received radiation or chemotherapy for this condition. Participation lasts about two years, during which researchers will closely monitor the safety and effectiveness of these treatments. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

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

Earlier studies have shown that HB-201 and HB-202 are generally well tolerated by patients. Initial results indicate that patients treated with HB-201 alone experienced stable disease and some positive effects, suggesting many can handle this treatment. When combined, HB-201 and HB-202 demonstrate similar safety results, indicating they could be viable options for treating head and neck cancer.

The chemotherapy drugs used in this study, carboplatin and paclitaxel, are well-known and widely used. They can cause side effects, but these are usually well understood and manageable. Overall, evidence suggests these treatments are tolerable, with safety remaining a key focus of ongoing research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine cutting-edge vaccines, HB-201 and HB-202, with traditional chemotherapy agents like carboplatin and paclitaxel. Unlike standard treatments for head and neck cancer, which typically involve surgery, radiation, or chemotherapy alone, this approach uses the vaccines to stimulate the immune system to better recognize and attack cancer cells. The unique feature here is the alternating doses of HB-201 and HB-202, which aim to enhance the immune response and potentially improve outcomes. This innovative combination may offer new hope by targeting cancer in a more precise and potent way.

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

Studies have shown that HB-201, one of the treatments in this trial, helped control the disease in 67% of head and neck cancer patients when used alone. This indicates that in more than half of the patients, the cancer did not worsen. In this trial, some participants will receive HB-201 combined with chemotherapy using carboplatin and paclitaxel. Research suggests that using HB-201 together with HB-202 (TheraT® vectors), another treatment arm in this trial, might be even more effective. These vaccines target HPV 16, a common virus linked to head and neck cancers. While detailed information on the combination's effectiveness is still being gathered, early results appear promising. The use of carboplatin and paclitaxel, well-known chemotherapy drugs, aims to further enhance the treatment's effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Ari Rosenberg, MD

Principal Investigator

University of Chicago - Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• HB-201
• HB-202
• Paclitaxel
• Transoral Robotic Surgery

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.

How Is the Trial Designed?

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 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

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 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]

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]

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]

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]

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 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]

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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05108870

Study Details | NCT05108870 | TheraT® Vectors (Vaccines ... 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 ...

2. ir.hookipapharma.com ir.hookipapharma.com/news-releases/news-release-details/hookipa-interim-phase-1-monotherapy-data-hb-201-treatment

HOOKIPA Interim Phase 1 Monotherapy Data of HB-201 for ... In these 15 patients, HB-201 demonstrated an unconfirmed response rate of 13%, a disease control rate of 67%, and a median PFS that is also ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-07603

Vaccines (TheraT Vectors) with Carboplatin and Paclitaxel ... This phase I/II trial tests the safety, side effects, best dose, and effectiveness of TheraT vectors (HB-201 and HB-202 vaccines) in combination with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10670496/

Head and Neck Squamous Cell Carcinoma Vaccine This review scope is to comprehensively gather existing evidence and summarize ongoing clinical trials focused on therapeutic vaccines for HNSCC treatment.

5. withpower.com withpower.com/trial/phase-2-hpv16-squamous-cell-carcinoma-3-2024-02992

HB-202/HB-201 for Head and Neck Cancer While specific data on HB-202/HB-201's effectiveness isn't detailed, similar HPV vaccines have shown potential in animal and early human trials. This suggests ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10056222/

Therapeutic Vaccination in Head and Neck Squamous Cell ... As per the preliminary analyses of the interim data from this ongoing trial, both HB-201 and HB-202/HB-201 are generally well tolerated and have been shown to ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/hookipa-debuts-phase-1-2-data/

Hookipa debuts Phase I/II data The company released Phase I/II clinical and safety data plus trial update for single and combination therapy for patients with HPV16+ head ...