CACTUX for Head and Neck Cancer

(CACTUX Trial)

Not currently recruiting at 5 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination called CACTUX to evaluate its effectiveness for individuals with certain types of head and neck cancer that cannot be cured with surgery or radiation. The study examines how the combination of drugs—cisplatin, nab-paclitaxel, and cetuximab—affects the cancer and identifies potential side effects. It targets individuals with a confirmed diagnosis of incurable head and neck cancer, especially if the cancer has spread or returned after previous treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that the CACTUX regimen is likely to be safe for humans?

Research shows that the treatments in the CACTUX regimen have undergone safety testing in people.

For nab-paclitaxel, studies suggest it is generally well-tolerated. When combined with cisplatin, nab-paclitaxel has demonstrated a good safety record, meaning most patients can manage the side effects.

Cisplatin, a common cancer treatment, has been used safely in many patients with head and neck cancer. However, some people might experience side effects like nausea or kidney problems. If issues with cisplatin arise, carboplatin often serves as an alternative. It is usually considered safe, with some potential for mild side effects.

Cetuximab has proven safe for people with head and neck cancer. Some common side effects include skin reactions and mild allergic responses.

Overall, the treatments in the CACTUX regimen have been studied in people, and the side effects are usually manageable. However, everyone reacts differently, so discussing expectations with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the CACTUX treatment for head and neck cancer because it combines nab-paclitaxel with cetuximab and either cisplatin or carboplatin, offering a potentially more effective approach. Nab-paclitaxel is a unique formulation that allows for improved delivery of the drug to cancer cells, potentially enhancing its effectiveness compared to standard treatments. Additionally, cetuximab targets the epidermal growth factor receptor (EGFR), which is often overexpressed in head and neck cancers, providing a more targeted attack against the cancer cells. This combination aims to increase efficacy while potentially reducing side effects associated with traditional chemotherapy.

What evidence suggests that the CACTUX regimen could be an effective treatment for head and neck cancer?

Research shows that the CACTUX treatment plan, which participants in this trial will receive, includes nab-paclitaxel, cisplatin (or carboplatin), and cetuximab, and may help treat head and neck cancer. Studies have found this combination effective for advanced cases of this cancer. Nab-paclitaxel replaces the usual drug, 5FU, and has shown positive results when used with cisplatin and cetuximab. This combination has been tested and may improve the overall response to treatment. While more research is needed, early results suggest this treatment could benefit patients with head and neck cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Douglas R Adkins, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27892728/

A Phase I/II Study of Nab-Paclitaxel, Cisplatin, and ... Nab-paclitaxel, cisplatin, cetuximab, and radiation were evaluated in patients with locally advanced head and neck cancer in this phase I/II trial.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00851877?term=AREA%5BConditionSearch%5D(%22Laryngeal%20Squamous%20Cell%20Carcinoma%22)%20AND%20AREA%5BInterventionSearch%5D(%22Albumin-Bound%20Paclitaxel%22)&rank=4

Study Details | Nab-Paclitaxel, Cisplatin, and Cetuximab ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6018

A randomized, controlled, open label, phase II clinical trial. 6018. Background: More than 60% of head and neck squamous cell carcinoma (HNSCC) patients (pts) were locally advanced at diagnosis.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2014-02222

Cisplatin, Nab-Paclitaxel, and Cetuximab in Treating ... This phase II trial studies how well cisplatin, nab-paclitaxel, and cetuximab work in treating patients with head and neck squamous cell carcinoma that has ...

5. redjournal.org redjournal.org/article/S0360-3016(10)02008-0/fulltext

Phase I Study of Nab-paclitaxel, Cisplatin and Cetuximab ... The purpose of this study is to determine the maximum tolerated dose of weekly nab-paclitaxel given concurrently with cetuximab, cisplatinum and radiotherapy

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

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

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19396017/

A phase II study of carboplatin and paclitaxel for recurrent ... The combination of carboplatin and paclitaxel is safe and moderately effective for the treatment of recurrent or metastatic head and neck cancer.

8. ascopubs.org ascopubs.org/doi/10.1200/jco.2006.24.18_suppl.15534

Safety and efficacy of the combination carboplatin ... Stable disease was seen in 2 patients (13.3%) and progressive disease was observed in 5 pts (33.3%). Toxicity was mild: we recorded 1 case of G3 toxicity ( ...

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

Weekly vs. 3‑weekly paclitaxel, carboplatin, and cetuximab ... The 1‑year progression‑free and overall survival rates were 27 and 46% for patients receiving weekly PCC, and 13 and 44% for patients receiving ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT05294900

Study Details | NCT05294900 | Trial of Neoadjuvant ... Objective: Primary objective: To evaluate the major pathologic response (mPR) of locally advanced head and neck cancer after paclitaxel and ...