Chemotherapy + Immunotherapy Before Surgery for Head and Neck Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with locally-advanced head and neck cancer. The aim is to determine if using both chemotherapy (including drugs like Carboplatin and Nab-paclitaxel) and immunotherapy (such as Durvalumab) before surgery can shrink tumors and improve long-term quality of life, potentially avoiding the harsh side effects of radiation. Patients who have not yet received treatment for this type of cancer and are eligible for surgery might be suitable candidates. Researchers hope this combination will be more effective and have fewer side effects than current standard treatments.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to advancements in cancer care.

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.

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

Research has shown that the combination of carboplatin, nab-paclitaxel, and durvalumab has been studied for safety in cancer patients. The FDA has already approved nab-paclitaxel for treating a type of lung cancer, indicating it is generally well-tolerated. Durvalumab has proven safe in various solid cancers, including head and neck cancer, and it aids the immune system in fighting cancer.

Studies also indicate that nab-paclitaxel combined with durvalumab has a tolerable safety profile. Patients have responded well to these treatments, experiencing manageable side effects. Although nab-paclitaxel and durvalumab are still under investigation for head and neck cancer, their use in other cancers provides reassurance about their safety.

Overall, this combination treatment is considered to have a reasonable safety profile, with side effects that patients in previous studies have managed effectively. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment approach for head and neck cancer because it combines chemotherapy, immunotherapy, and surgery in a novel sequence. Unlike traditional treatments that may start with surgery followed by chemotherapy or radiation, this regimen uses carboplatin, nab-paclitaxel, and durvalumab before surgery to potentially shrink tumors and enhance surgical outcomes. Durvalumab, an immunotherapy drug, helps the immune system target cancer cells more effectively, which is not typically included in standard care for this condition. This multi-step, integrated approach could improve survival rates and reduce recurrence, offering hope for better patient outcomes.

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

Research has shown that patients who used a similar chemotherapy treatment often experienced significant cancer shrinkage. About one-third of these patients achieved a complete response, meaning their cancer was eliminated. In this trial, participants in the various treatment arms will receive a form of paclitaxel that is more effective against certain cancers than the regular version. The FDA has approved this form for lung cancer, and it has shown potential in treating head and neck cancer. Durvalumab, a drug that boosts the immune system, is also part of the treatment regimen in this trial and has shown positive effects in head and neck cancer patients. By combining these treatments, the trial aims to improve patient response and reduce side effects compared to standard treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Jared Weiss, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

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

I agree to use birth control during the study.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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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

Published Research Related to This Trial

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]

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 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]

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 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]

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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9470832/

Effectiveness of paclitaxel and carboplatin combination in ... Four patients (17%) achieved a complete response and 5 (22%) a partial response for an overall response rate of 39%. Duration of response was 3-9 months.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17675395/

Long-term outcomes with concurrent carboplatin, paclitaxel ... Forty of 50 assessable patients (80%) had an objective response, with a complete response rate of 52%. With a median follow-up of 69 months for surviving ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)41203-9/fulltext

Long-term outcomes with concurrent carboplatin, paclitaxel ... Treatment with concurrent carboplatin, paclitaxel and radiation is safe and offers curative potential for poor prognosis patients with locally advanced SCCHN.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00176267

Paclitaxel, Carboplatin And Low Dose Radiation As ... This study is being performed utilizing two cycles of Paclitaxel and Carboplatin, plus low doses radiation as initial therapy prior to other treatment (surgery ...

5. spandidos-publications.com spandidos-publications.com/10.3892/mco.2021.2403

Weekly vs. 3‑weekly paclitaxel, carboplatin, and cetuximab ... Overall response rates were 44.4% with a median PFS of 6.2 months and a median OS of 14 months. Although these results were promising, in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02250326

NCT02250326 | Safety and Efficacy Study of Nab®- ... This is a Phase 2, open-label, multicenter study to assess the efficacy and safety of second/third-line treatment with nab-paclitaxel in combination with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03174275

Carboplatin, Nab-Paclitaxel, Durvalumab Before Surgery ... 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...

9. moffitt.org moffitt.org/clinical-trials-and-studies/clinical-trial-23250/

Clinical Trial 23250 Secondary Objective: The secondary objective is to evaluate the safety of nab-paclitaxel + Durvalumab (MEDI4736) + tremelimumab + neoantigen vaccine vs. nab- ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/761270Orig1s000MultidisciplineR.pdf

761270Orig1s000 - accessdata.fda.gov ... carboplatin); HNSCC Head and neck squamous cell carcinoma; MTD ... signal evaluation based on emerging safety data from all data sources ( ...