Chemotherapy + Immunotherapy Before Surgery for Head and Neck Cancer

Recruiting at 1 trial location

Overseen By Melissa Flores

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Immunosuppressants, PD-1/PD-L1 inhibitors

Disqualifiers: Metastatic disease, Tuberculosis, Pneumonitis, 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

Compensation: Varies

Number of Visits: Unknown

39 Participants Needed

Trial Summary

What is the purpose of this trial?

Participants in this study have a type of cancer called squamous cell carcinoma of the head and neck (SCCHN). Their SCCHN has spread around the area where the cancer first started. This is called locally-advanced SCCHN. These participants are eligible for surgery. Previous research with a similar therapy regimen resulted in high rates of cancer shrinkage, high rates of avoiding radiation and its side effects, high cure rate and good quality of life. Radiation can be very toxic. The purpose on this study is to try to avoid radiation. If the participants are not on this study they would be receiving radiation as it is standard treatment of their cancer. In the last study with a similar regimen, about a third of cancers had a pathologic complete response with the first part of the study. This means that the chemotherapy had killed the cancer. The investigators are trying to improve the regimen further with a goal of increasing this rate of complete response to the first part of therapy. The investigators also hope that by improving results in the first part, that more people will be cured and that long term quality of life (especially speech and swallowing) will be improved, both compared to standard therapies and to the last study. Doctors do not know how this therapy will effect the participants. There is no guarantee that this study will benefit the participants. The prior study used a combination of chemotherapy consisting of carboplatin, paclitaxel and a third targeted anti-cancer drug. In this study the investigators are testing the combination of carboplatin, nano-albumin bound paclitaxel and durvalumab. Nano-albumin bound paclitaxel has been shown to be more active against other types of squamous cancers than regular paclitaxel. It is FDA approved for squamous lung cancer, but experimental for head and neck cancer. Durvalumab is an experimental drug that uses the body's own immune system to fight the cancer. Doctors hope that combining Durvalumab with 2 chemotherapy drugs will be effective in treating SCCHN. Durvalumab on its own has been studied in patients with SCCHN and initial results have shown that some subjects' cancer has responded to it. The purpose of this study is to test a combination of chemotherapy to hopefully both increase the number of subjects that respond to therapy while also decreasing the number of side effects that subjects experience.

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 be on any other chemotherapy, investigational drugs, or immunosuppressive medications within 14 days before starting the trial.

What data supports the effectiveness of the drugs used in the Chemotherapy + Immunotherapy Before Surgery for Head and Neck Cancer trial?

Research shows that paclitaxel and carboplatin are active in treating advanced head and neck cancer, potentially preserving organs and improving quality of life. Additionally, a combination of carboplatin, paclitaxel, and immune checkpoint inhibitors has shown high response rates in patients with recurrent or metastatic head and neck cancer. ^{1 2 3 4 5}

Is the combination of chemotherapy and immunotherapy before surgery for head and neck cancer safe?

The combination of nab-paclitaxel (a form of chemotherapy) and carboplatin has been studied in various cancers and is generally considered safe, with a lower rate of severe side effects like neutropenia (low white blood cell count) compared to other formulations. Nab-paclitaxel is FDA approved for several adult cancers, indicating its safety profile is well-established. ^{5 6 7 8 9}

How is the chemotherapy and immunotherapy drug combination unique for head and neck cancer?

This treatment combines chemotherapy drugs (Carboplatin and Nab-paclitaxel) with an immunotherapy drug (Durvalumab) before surgery, aiming to shrink tumors and preserve organs, potentially improving quality of life compared to traditional surgery and radiation alone. ^{1 10 11 12 13}

Research Team

Jared Weiss, MD

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

This trial is for adults with a type of cancer called squamous cell carcinoma of the head and neck, which hasn't spread beyond its original location and can be surgically removed. Participants must have good performance status, measurable disease, proper bone marrow function, and adequate liver and kidney function. They should not have had major surgery recently or suffer from active serious infections or certain autoimmune diseases.

Inclusion Criteria

Signed an institutional review board (IRB)-approved informed consent and HIPAA authorization

I agree to use birth control during the study.

Women who can have babies must have a negative pregnancy test within 72 hours before starting the treatment.

Exclusion Criteria

Receiving any investigational agent currently or within 28 days or 5 half-lives of Day 1 of treatment on this study, whichever is shorter

I do not have active liver or bile duct disease, except for Gilbert's syndrome, gallstones without symptoms, or stable chronic liver disease.

My cancer has spread to other parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Induction Chemotherapy

Participants receive 6 weeks of induction chemotherapy with carboplatin, nab-paclitaxel, and durvalumab

6 weeks

Weekly cycles of chemotherapy, durvalumab every two weeks

Surgical Resection

Tumor imaging followed by surgical resection within 1-4 weeks post induction

1-4 weeks

Adjuvant Therapy

Risk-adapted adjuvant therapy with durvalumab or chemoradiation based on risk category

6 weeks

Follow-up

Participants are monitored for progression and survival every three months for 18 months, then per standard of care

18 months

Every three months

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Durvalumab
• IMRT
• Nab-paclitaxel
• Surgical resection

Trial Overview The study tests a combination of chemotherapy drugs (carboplatin and nab-paclitaxel) with an immunotherapy drug (durvalumab), before surgical removal of the tumor. The goal is to shrink tumors without radiation therapy's side effects, hoping to improve cure rates and long-term quality of life related to speech and swallowing.

Participant Groups

Group I: Medium Risk Experimental Treatment 6 Interventions

Part 1- Patients receive 6 weeks of induction chemotherapy comprised of weekly cycles of carboplatin dosed to an Area Under the Curve (AUC2) and nab-paclitaxel 100 mg/m2 X 6 cycles in combination with durvalumab 750 mg administered once every two weeks for 5 cycles (D1 of weeks 1, 3, 5, 7, and 9). Part 2- Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection. Part 3- patients receive ipsilateral involved field radiation concurrent with weekly cisplatin 30mg/m2. Once chemoradiotherapy is complete these patients will receive durvalumab 750 mg every two weeks for 3 cycles.

Group II: Low Risk Experimental Treatment 4 Interventions

Part 1- Patients receive 6 weeks of induction chemotherapy comprised of weekly cycles of carboplatin dosed to an Area Under the Curve (AUC2) and nab-paclitaxel 100 mg/m2 X 6 cycles in combination with durvalumab 750 mg administered once every two weeks for 5 cycles (D1 of weeks 1, 3, 5, 7, and 9). Part 2- Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection. Part 3- patients receive adjuvant durvalumab (750 mg) once every two weeks x 3 cycles

Group III: High Risk Experimental Treatment 6 Interventions

Part 1- Patients receive 6 weeks of induction chemotherapy comprised of weekly cycles of carboplatin dosed to an Area Under the Curve (AUC2) and nab-paclitaxel 100 mg/m2 X 6 cycles in combination with durvalumab 750 mg administered once every two weeks for 5 cycles (D1 of weeks 1, 3, 5, 7, and 9). Part 2- Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection. Part 3- All patients will be treated with intensity modulation radiation therapy (IMRT) concurrent with weekly cisplatin 30mg/m2 or other standard of care chemoradiotherapy regimen.Once chemoradiotherapy is complete these patients will receive durvalumab 750 mg every two weeks for 3 cycles.

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?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

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Celgene

Chief Medical Officer since 2016

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Celgene

Chief Executive Officer since 2016

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Industry Sponsor

Trials

4,491

Recruited

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Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

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 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 study involving 37 patients with advanced squamous cell lung cancer (SQCLC), the combination of gemcitabine and albumin-bound paclitaxel (ABP) achieved a high overall response rate (ORR) of 59%, indicating significant antitumor efficacy.

The treatment was found to be safe and well-tolerated, with a median progression-free survival (PFS) of 7.5 months, outperforming traditional carboplatin doublet regimens and showing comparable efficacy to more complex combinations like carboplatin plus taxane plus pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Albumin-Bound Paclitaxel and Gemcitabine in Patients with Newly Diagnosed Stage IV Squamous Cell Lung Cancers. Paik, PK., Kim, RK., Ahn, L., et al.[2022]

A phase I study is being conducted to evaluate the safety and determine the maximum tolerated dose of albumin-bound paclitaxel (ABP) delivered via pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal metastases from various cancers.

The study will involve three treatments with ABP, escalating the dose from 35 to 140 mg/m², and will assess not only toxicity but also factors like surgical morbidity and quality of life, aiming to set the stage for future randomized phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. Van De Sande, L., Graversen, M., Hubner, M., et al.[2023]

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

In a phase II trial involving 45 patients with advanced gastric cancer, the combination of nab-paclitaxel and ramucirumab achieved an overall response rate of 54.8%, indicating significant efficacy as a second-line treatment.

The treatment was associated with manageable side effects, primarily decreased neutrophil and white blood cell counts, but no treatment-related deaths occurred, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. Bando, H., Shimodaira, H., Fujitani, K., et al.[2023]

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

ABI-007, a novel formulation of paclitaxel, can be safely administered at higher doses than traditional paclitaxel formulations, with maximum-tolerated doses of 100 mg/m² for heavily pretreated patients and 150 mg/m² for lightly pretreated patients.

The study showed partial antitumor responses in patients with breast, lung, and ovarian cancers, indicating that ABI-007 may be effective even in those previously treated with standard paclitaxel formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. Nyman, DW., Campbell, KJ., Hersh, E., et al.[2022]

In a study of 62 patients with advanced head and neck carcinoma, induction chemotherapy with paclitaxel and carboplatin resulted in a 66% overall response rate, indicating significant efficacy in this challenging patient population, most of whom had Stage IV disease.

The treatment was well tolerated, and organ preservation was achieved in 45% of patients, highlighting the potential for maintaining quality of life while improving survival outcomes, particularly in responders with oropharyngeal and hypopharyngeal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 an 1999. Dunphy, FR., Dunleavy, TL., Harrison, BR., et al.[2015]

In a phase II study involving 41 patients with recurrent or metastatic head and neck cancer, the combination of paclitaxel and carboplatin showed an overall response rate of 20%, with particularly promising results in nasopharyngeal cancer where 50% of evaluable patients achieved a complete response.

The treatment was associated with manageable acute and cumulative toxicities, with grade 3 to 4 side effects occurring in a small percentage of patients, indicating that the combination is both active and relatively safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study. Fountzilas, G., Athanassiadis, A., Samantas, E., et al.[2015]

References

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

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

2. 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]

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

A Phase II Trial of Albumin-Bound Paclitaxel and Gemcitabine in Patients with Newly Diagnosed Stage IV Squamous Cell Lung Cancers. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. [2023]

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

A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma : a North Central Cancer Treatment Group Study, N057E(1). [2021]

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

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). [2022]

7. England pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. [2018]

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

Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. [2022]

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

Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 an 1999. [2015]

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

A phase I report of paclitaxel dose escalation combined with a fixed dose of carboplatin in the treatment of head and neck carcinoma. [2015]

12. Germany pubmed.ncbi.nlm.nih.gov

PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study. [2023]

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

Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study. [2015]