Duvelisib Plus Docetaxel In Recurrent/Metastatic HNSCC

Phase 2

Active, not recruiting

Conditions: Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Recurrent Squamous Cell Carcinoma of the Head and Neck
Metastatic Head and Neck Cancer
Advanced Head and Neck Cancer
Advanced Head and Neck Squamous Cell Carcinoma

Interventions: Drug: Duvelisib
Drug: Docetaxel

Registration Number: NCT05057247

Lead Sponsor: Glenn J. Hanna

Brief Summary: 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

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 26

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Duvelisib plus Docetaxel chemotherapy	Docetaxel	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.
Duvelisib plus Docetaxel chemotherapy	Duvelisib	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.

Primary Outcome Measures

Name	Time	Method
Best Overall Response (BOR) Rate	Median time on treatment was 2.3 months (range 0.7-21.9 months)	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.

Secondary Outcome Measures

Name	Time	Method
Median Overall Survival (OS)	The median follow-up time was 6.5 months (range 0.7 - 26 months).	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.
Median Progression Free Survival (PFS)	Median follow-up time was 2.3 months (range 0.7-21.9 months)	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.
Duration of Response (DOR)	Median follow-up time was 2.3 months (range 0.7-21.9 months)	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.
Number of Participants With Treatment Related Adverse Events Per CTCAE 5.0	Median follow-up time was 2.3 months (range 0.7-21.9 months)	The number of participants who experienced the treatment-related adverse events per CTCAE 5.0 during the time of treatment.
Change of QLQ H&N 35 From Cycle 1 to Cycle 4	Up to 3 months	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.