CACTUX for Head and Neck Cancer

(CACTUX Trial)

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Antiretrovirals, Investigational agents

Disqualifiers: Brain metastases, Peripheral neuropathy, 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: 6

Duration: 18 weeks

74 Participants Needed

Trial Summary

Do I need to stop taking my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your current medications with the trial team to get specific guidance.

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

Research shows that the CACTUX regimen, which includes nab-paclitaxel, cetuximab, and carboplatin, may lead to longer progression-free survival in head and neck cancer compared to historical treatments. Additionally, nab-paclitaxel has demonstrated a higher response rate in similar cancers, suggesting improved drug delivery and effectiveness. ^{1 2 3 4 5}

Is the CACTUX treatment generally safe for humans?

The CACTUX treatment, which includes nab-paclitaxel, cetuximab, and carboplatin, has shown favorable safety results in studies for head and neck cancer and other conditions like lung cancer. Nab-paclitaxel, in particular, avoids some toxicities associated with other formulations, making it a safer option. ^{1 3 6 7 8}

What makes the CACTUX drug regimen unique for head and neck cancer?

The CACTUX regimen is unique because it uses nab-paclitaxel, a nanoparticle albumin-bound formulation of paclitaxel, which enhances drug delivery into tumors by exploiting the cancer cells' nutrient uptake mechanisms, potentially leading to longer progression-free survival compared to traditional treatments. ^{1 2 3 5 9}

What is the purpose of this trial?

The purpose of this research study is to look at the effect of a treatment regimen called CACTUX on head and neck cancer. The CACTUX regimen is a combination of three drugs called cisplatin, nab-paclitaxel, and cetuximab (although carboplatin may be given in place of cisplatin if participants have previously had problems receiving cisplatin). The use of nab-paclitaxel in this combination is different from routine care, in which a drug called 5FU is often given instead, but the investigators group has conducted previous research where the investigators incorporated nab-paclitaxel into routine treatment with cisplatin, 5FU, and cetuximab. The investigators are looking at the incidence of side effects with the CACTUX regimen as well as response of the disease and health status.

Research Team

Douglas R Adkins, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Adults with incurable head and neck squamous cell carcinoma (HNSCC) that's metastatic or unresectable in a previously irradiated area. They must have measurable disease, be at least 4 months post-curative therapy if applicable, and have good organ function. Participants need to agree to contraception use during the study and for 3 months after. Exclusions include allergies to trial drugs, prior systemic therapy for incurable disease, pregnancy/breastfeeding, certain other cancers within 2 years, brain metastases, uncontrolled illnesses or HIV on antiretroviral therapy.

Inclusion Criteria

Availability of diagnostic tumor tissue specimens for correlative studies

Ability to understand and sign an IRB approved informed consent document

My blood, kidney, and liver functions are all within normal ranges.

Exclusion Criteria

I have had cancer other than my current one in the last 2 years, with some exceptions.

I have cancer that has spread to my brain.

I am HIV positive and on antiretroviral therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the CACTUX regimen consisting of nab-paclitaxel, cisplatin (or carboplatin), and cetuximab for up to 6 cycles

18 weeks

3 visits per 21-day cycle (in-person)

Maintenance Therapy

Participants receive maintenance therapy with nab-paclitaxel and cetuximab

8 months

3 visits per 21-day cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Carboplatin
• Cetuximab
• Cisplatin
• Nab-paclitaxel

Trial Overview The CACTUX regimen is being tested which includes cisplatin (or carboplatin), nab-paclitaxel, and cetuximab. This combination aims to treat head and neck cancer differently from standard care by substituting nab-paclitaxel for the usual drug 5FU. The trial will assess side effects as well as how well the cancer responds and overall health status of participants.

Participant Groups

Group I: CACTUX: nab-paclitaxel, cisplatin (or carboplatin), cetuximab Experimental Treatment 4 Interventions

Up to 6 cycles of CACTUX may be given. The CACTUX regimen consists of: * nab-paclitaxel given intravenously over 30 minutes on an outpatient basis on Days 1, 8, and 15 of each 21-day cycle followed by * cisplatin given intravenously over 60 minutes on an outpatient basis OR carboplatin AUC5 given intravenously over 30 minutes on an outpatient basis on Day 1 of each 21-day cycle followed by * cetuximab given intravenously on an outpatient basis of Days 1, 8, and 15 of each 21-day cycle * Cisplatin or carboplatin may be given at the discretion of the investigator. After the completion of 6 cycles of CACTUX, maintenance therapy will be given and consists of: * nab-paclitaxel given intravenously over 30 minutes on an outpatient basis on Days 1 and 8 of each 21-day cycle * cetuximab given intravenously on an outpatient basis on Days 1, 8, and 15 of each 21-day cycle

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?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Findings from Research

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]

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]

The combination of carboplatin, oral tegafur, and cetuximab is a safe and well-tolerated first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), with a high compliance rate among patients.

In a study of 104 patients, the treatment resulted in a median overall survival of 11 months and a progression-free survival of 6 months, with an overall response rate of 35%, indicating its efficacy in managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous 5-Fluorouracil in Patients With Advanced Squamous Cell Carcinoma: A Retrospective Study. Buxó, E., Sosa, A., Reig, O., et al.[2019]

In a study of 40 patients with stage III/IV squamous non-small-cell lung cancer, the combination of nab-paclitaxel and a platinum agent (cisplatin or carboplatin) resulted in a high overall response rate of 62.5% and a disease control rate of 92.5%, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse effects being mild to moderate (grade 1 to 2), including myelosuppression and gastrointestinal issues, suggesting that nab-paclitaxel combined with platinum agents is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. Fang, Y., Wang, L., Xia, GH., et al.[2022]

In a phase III trial involving 1,052 patients with advanced non-small-cell lung cancer, nab-paclitaxel plus carboplatin showed a significantly higher overall response rate (33%) compared to solvent-based paclitaxel plus carboplatin (25%), indicating greater efficacy in treatment.

Nab-paclitaxel was associated with fewer severe side effects, such as neuropathy and neutropenia, compared to solvent-based paclitaxel, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. Socinski, MA., Bondarenko, I., Karaseva, NA., 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel with cetuximab and carboplatin as first-line therapy for recurrent or metastatic head and neck cancer: A single-arm, multicenter, phase 2 trial. [2022]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Induction chemotherapy with carboplatin, nab-paclitaxel and cetuximab for at least N2b nodal status or surgically unresectable squamous cell carcinoma of the head and neck. [2019]

4. 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]

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

Intravenous 5-Fluorouracil in Patients With Advanced Squamous Cell Carcinoma: A Retrospective Study. [2019]

6. Thailand pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. [2022]

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

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy as second-line therapy of cytotoxic anticancer drugs in patients with advanced non-small cell lung cancer. [2022]

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

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. [2022]

9. 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]