Duvelisib Plus Docetaxel In Recurrent/Metastatic HNSCC

A Phase II Study of Duvelisib Plus Docetaxel in PD-1 Inhibitor Experienced Patients With Incurable Head and Neck Squamous Cell Carcinoma

This trial that is investigating a medication called duvelisib in combination with docetaxel for the treatment of squamous cell carcinoma of the head and neck (SCCHN) that has returned or spread outside the head and neck area.

The names of the study drugs involved in this study are:

• Duvelisib (PI3K inhibitor)
• Docetaxel chemotherapy

Study Overview

• Status: Completed
• Conditions: Metastatic Head and Neck Cancer; Advanced Head and Neck Squamous Cell Carcinoma; Recurrent Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma of the Head and Neck (SCCHN); Advanced Head and Neck Cancer
• Intervention / Treatment: Drug: Duvelisib; Drug: Docetaxel

Detailed Description

This multicenter, phase II open-label, single-arm trial will enroll participants with recurrent or metastatic (R/M), incurable squamous cell carcinoma of the head and neck (SCCHN) who have failed or discontinued PD-1 blockade in the first-line (1L) advanced disease setting, regardless of human papillomavirus (HPV) and smoking status, or PI3K pathway alteration status.

This research study involves the oral (taken by mouth) agent duvelisib with the intravenous (IV) chemotherapy agent docetaxel.

The names of the study drugs involved in this study are:

• Duvelisib (PI3K inhibitor)
• Docetaxel chemotherapy

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

Participants will receive study treatment for up to 2 years and will be followed for 3 years.

It is expected that about 30 people will take part in this research.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug (duvelisib) to learn whether it works in treating a specific disease. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has not approved duvelisib for this specific disease but has approved it for other uses (such as certain types of blood cancers). The FDA has approved docetaxel as a treatment option for head and neck cancer, as well as other cancer types.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Participants must have histologically confirmed squamous cell carcinoma of the head and neck (SCCHN) with evidence of recurrent, metastatic (R/M) or advanced, incurable disease from any mucosal subsite including oral cavity, oropharynx, larynx, hypopharynx, nasal cavity, and the paranasal sinuses.
• Participants must have at least one RECIST v1.1 measurable lesion, as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) ≥1 cm with CT scans or MR imaging.

• Must have had at least 1, but no more than 2, prior lines of prior systemic therapy for R/M SCCHN; one of these lines should have included PD-1/L1 blockade

  • Platinum-based therapy as part of definitive/adjuvant or curative-intent treatment can count as 1 prior line of therapy if the subject progressed within 6 months of receiving therapy.
  • At least 2 weeks must have elapsed since the end of prior chemotherapy, biological agents (3 weeks for anti-cancer monoclonal antibody containing regimens) or any investigational drug product, with adequate recovery of treatment-related toxicity to NCI CTCAE Version 5.0 grade ≤1 (or tolerable grade 2) or back to baseline (except for alopecia or peripheral neuropathy).
• Be ≥18 years of age on the day of signing informed consent.
• Must provide prior data on tumor PD-L1 expression status and HPV status, if available
• Have a performance status of 0 or 1 on the ECOG Performance Scale

• Participants must have adequate organ and marrow function as defined below (within 14 days prior to study registration):

  • absolute neutrophil count ≥ 1,000/mcL
  • hemoglobin ≥ 9 g/dL
  • platelets ≥ 100,000/mcL
  • total bilirubin ≤ upper limit of normal (ULN)
  • AST(SGOT)/ALT(SGPT) ≤ 2.5x institutional ULN (or ≤ 1.5x institutional ULN if concomitant with alkaline phosphatase >2.5x institutional ULN) or ≤ 5x ULN for those with liver metastases
  • serum creatinine ≤ 1.5x ULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above 1.5x ULN
  • coagulation profile INR ≤ 1.5x ULN unless the participant is receiving an anticoagulant
• Baseline tumor measurements must be documented from imaging within 28 days prior to study registration.
• Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 7 days of study registration. Female subjects of childbearing potential should have a negative urine or serum pregnancy test repeated within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female and male subjects of childbearing potential must agree to use an adequate method of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of stud drug administration. Contraception is required before starting the first dose of study medication through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Be willing and able to provide written informed consent for the trial.

Exclusion Criteria:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.

• Have been previously treated with 3 or more lines of systemic therapy for R/M SCCHN.

  -- Have received treatment with a prior PI3K pathway inhibitor

• Have received radiation therapy (RT) within 14 days of the first dose of duvelisib on study.
• Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging and off systemic steroids for at least 4 weeks prior to the first dose of study treatment), and have no evidence of new or enlarging brain metastases. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability, because of the poor prognosis and progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Concurrent administration of other cancer specific therapy or investigational agents during the course of this study.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection; evidence of symptomatic congestive heart failure, unstable angina pectoris, stroke, or ventricular arrhythmia within 6 months of enrollment.
• Have received a live or live attenuated vaccine within 4 weeks of the first dose of duvelisib.
• Have received medications or consumed foods that are strong inhibitors or inducers of cytochrome P450 (CYP3A) within 2 weeks of, or while on, duvelisib.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Duvelisib plus Docetaxel chemotherapy; 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.

Drug: Duvelisib; Duvelisib capsules should be swallowed whole with a glass of water (approximately 8 ounces). Advise patients not to open, break, or chew the capsules. Duvelisib may be administered without regard to meals; however, subjects should avoid grapefruit and grapefruit juice while on duvelisib. continue for up to 24 months.; Other Names: VS-0145; Drug: Docetaxel; Docetaxel chemotherapy once every 21 days (by intravenous infusion) over about 30- 60 minutes at each visit. This will continue for up to 24 months; Other Names: Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response (BOR) Rate	BOR rate was defined as the proportion of participants that experienced complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.	Median time on treatment was 2.3 months (range 0.7-21.9 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Overall Survival (OS)	OS based on the Kaplan-Meier method was defined as the time from registration to death due to any cause, or censored at date last known alive.	The median follow-up time was 6.5 months (range 0.7 - 26 months).
Median Progression Free Survival (PFS)	PFS based on the Kaplan-Meier method was defined as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.	Median follow-up time was 2.3 months (range 0.7-21.9 months)
Duration of Response (DOR)	DOR was measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Median follow-up time was 2.3 months (range 0.7-21.9 months)
Number of Participants With Treatment Related Adverse Events Per CTCAE 5.0	The number of participants who experienced the treatment-related adverse events per CTCAE 5.0 during the time of treatment.	Median follow-up time was 2.3 months (range 0.7-21.9 months)
Change of QLQ H&N 35 From Cycle 1 to Cycle 4	The QLQ H&N35 incorporates seven multi-item scales that assess pain, swallowing, senses (taste and smell), speech, social eating, social contact and sexuality. There are also eleven single items. The score range from 0 to 100. For all items and scales, high scores indicate more problems, so negative difference indicates better QoL (less problems) at C4D1 compared to C1D1.	Up to 3 months

Collaborators and Investigators

• Sponsor: Glenn J. Hanna
• Collaborators: Secura Bio, Inc.
• Investigators: Principal Investigator: Glenn J. Hanna, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2021
• Primary Completion (Actual): October 1, 2023
• Study Completion (Actual): June 13, 2024

Study Registration Dates

• First Submitted: September 8, 2021
• First Submitted That Met QC Criteria: September 15, 2021
• First Posted (Actual): September 27, 2021

Study Record Updates

• Last Update Posted (Estimated): October 31, 2025
• Last Update Submitted That Met QC Criteria: October 28, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Recurrent Squamous Cell Carcinoma of the Head and Neck; Squamous cell carcinoma of the head and neck (SCCHN); Advanced Head and Neck Cancer; Metastatic Head and Neck Cancer; Advanced Head and Neck Squamous Cell Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; duvelisib
• Other Study ID Numbers: 21-393

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No