Duvelisib + Docetaxel for Head and Neck Cancer

Overseen By Glenn J. Hanna, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Glenn J. Hanna

Must not be taking: PI3K inhibitors, CYP3A inducers

Disqualifiers: CNS metastases, Carcinomatous meningitis, 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: 22

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for squamous cell carcinoma of the head and neck (SCCHN), a type of cancer that has recurred or metastasized. It combines two drugs, duvelisib (which affects cancer cell growth) and docetaxel (a chemotherapy drug), to evaluate their combined effectiveness. Individuals with SCCHN that has returned or spread, who have undergone one or two prior treatments, and have at least one measurable tumor are suitable candidates for this trial. Participants will receive these drugs in a 21-day cycle, continuing for up to 24 months unless the cancer progresses or side effects become too severe. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take medications or foods that strongly affect a liver enzyme called CYP3A within 2 weeks of starting duvelisib or during the study.

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

Research has shown that combining duvelisib and docetaxel may help treat head and neck cancer. In earlier studies, patients generally tolerated this combination well. Most side effects were mild to moderate, such as fatigue and low blood cell counts. More serious side effects occurred but were less common. Notably, this combination proved effective for patients whose cancer recurred or spread after other treatments. While the treatment shows promise for many, ongoing studies aim to ensure its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Duvelisib and Docetaxel for head and neck cancer because it offers a new mechanism of action. While standard treatments often involve surgery, radiation, and chemotherapy, Duvelisib, taken orally, targets specific pathways in cancer cells that help them grow and survive. This is different from traditional chemotherapy, which attacks all rapidly dividing cells. By combining Duvelisib with Docetaxel, which is a well-known chemotherapy drug, researchers hope to enhance the treatment's effectiveness and potentially reduce side effects by precisely targeting cancer cells.

What evidence suggests that this treatment might be an effective treatment for head and neck cancer?

This trial will evaluate the combination of two treatments, duvelisib and docetaxel, for head and neck squamous cell carcinoma (SCCHN) that has recurred or spread. Duvelisib blocks signals that help cancer cells grow, while docetaxel is a chemotherapy that kills cancer cells. Research has shown that these treatments work well together, especially for patients who did not respond to anti-PD-1 immune therapy. This combination targets cancer by halting growth signals and using chemotherapy to destroy the cells. Although more research is needed, early results are promising for patients with this challenging form of cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Glenn J. Hanna, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), who have had no more than two prior systemic therapies, one including PD-1/L1 blockade. They must not have used PI3K inhibitors before, be in good health otherwise, and agree to use contraception.

Inclusion Criteria

My blood, liver, and kidney functions meet the study's health requirements.

I can provide information on my tumor's PD-L1 and HPV status.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have cancer that has spread to my brain or spinal cord.

I have not taken strong CYP3A affecting drugs or foods within 2 weeks of starting duvelisib.

I am not taking any other cancer treatments or experimental drugs during this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive duvelisib orally twice daily and docetaxel via IV on day 1 of each 21-day cycle for up to 24 months

24 months

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Duvelisib

Trial Overview The trial is testing duvelisib combined with docetaxel chemotherapy in patients with SCCHN that has returned or spread. Duvelisib is a PI3K inhibitor which may help stop cancer growth by targeting specific cells.

How Is the Trial Designed?

Group I: Duvelisib plus Docetaxel chemotherapy Experimental Treatment 2 Interventions

Participants will receive duvelisib by mouth twice daily,dosage per protocol continuously (days 1-21 of a 21-day cycle) with a 7-day lead-in planned prior to the start of taxane therapy. Docetaxel at via IV will be delivered on day 1 of each 21-day cycle. Treatment will continue for 24-months or until unacceptable toxicity, progression, or death.

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

Glenn J. Hanna

Lead Sponsor

Trials

6

Recruited

160+

Secura Bio, Inc.

Industry Sponsor

Trials

9

Recruited

200+

Published Research Related to This Trial

In a phase II study involving 31 patients with advanced squamous cell carcinoma of the head and neck, docetaxel demonstrated significant activity, with a major response rate of 42% and a median response duration of 5 months.

Docetaxel was well tolerated, with manageable side effects such as leukopenia and fatigue, and the use of premedication helped reduce the incidence of severe toxicities, allowing for safe outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: an active drug for squamous cell carcinoma of the head and neck. Dreyfuss, AI., Clark, JR., Norris, CM., et al.[2018]

In a phase III study involving 358 patients with advanced head and neck cancer, adding docetaxel to cisplatin and 5-fluorouracil (TPF) improved overall survival and reduced toxicity compared to the PF regimen.

Patients receiving TPF showed a trend towards better health-related quality of life (HRQOL) and experienced greater improvements in swallowing and coughing issues during treatment, suggesting that TPF may enhance patient well-being alongside survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). van Herpen, CM., Mauer, ME., Mesia, R., et al.[2022]

Docetaxel shows promising efficacy as a treatment for recurrent squamous cell cancer of the head and neck, with response rates between 33% to 44% when combined with cisplatin, and median survival times of 9.6 to 11 months.

In the neoadjuvant setting, docetaxel has demonstrated response rates greater than 90%, indicating its potential for improving disease-free and overall survival, with ongoing trials comparing its effectiveness to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. Glisson, BS.[2018]

The combination of docetaxel and cisplatin demonstrated a significant overall response rate of 53.7% in patients with locally advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, indicating its efficacy as a treatment option.

Despite common hematologic and non-hematologic toxicities, the treatment was generally well-tolerated, with serious adverse effects being infrequent due to the use of corticosteroid prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. Schöffski, P., Catimel, G., Planting, AS., et al.[2020]

In a phase I/II trial involving 22 patients with recurrent/metastatic head and neck cancer, the combination of docetaxel and pembrolizumab showed a 22.7% overall response rate, indicating potential efficacy in this difficult-to-treat population.

The treatment was associated with manageable side effects, with myelosuppression being the most common adverse event, while serious immune-related side effects were relatively rare, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. Fuereder, T., Minichsdorfer, C., Mittlboeck, M., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39625478

Duvelisib with Docetaxel for Patients with Anti-PD-1 ... We report a favorable response rate when combining a selective PI3K pathway inhibitor and taxane in patients with anti-PD-1 refractory ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6031

Duvelisib with docetaxel for patients with anti-PD-1 ... We report a favorable response rate when combining a PI3K pathway inhibitor with taxane chemotherapy in patients with anti-PD-1 refractory HNSCC.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11831104/

Duvelisib with Docetaxel for Patients with Anti–PD-1 ... Results of a randomised phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J Cancer 2004;40:2071–6.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05057247

Duvelisib Plus Docetaxel In Recurrent/Metastatic HNSCC This trial that is investigating a medication called duvelisib in combination with docetaxel for the treatment of squamous cell carcinoma of the head and ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-24-2262/750391/am/Duvelisib-with-docetaxel-for-patients-with-anti-PD

Duvelisib with docetaxel for patients with anti-PD-1 refractory ... Supplementary data. Data from Duvelisib with Docetaxel for Patients with Anti–PD-1 Refractory, Recurrent, or Metastatic Head and Neck Squamous Cell Carcinoma.

6. aacrjournals.org aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-24-2262/3523179/ccr-24-2262.pdf

Duvelisib with docetaxel for patients with anti-PD-1 refractory ... Results of a randomised phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J. Cancer.