Duvelisib Plus Docetaxel In Recurrent/Metastatic HNSCC

Study Overview
=================
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.

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

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

Intervention / Treatment
-----------------
* Drug: Duvelisib
* Drug: Docetaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duvelisib plus Docetaxel chemotherapy<br>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<br>* 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.<br>* Other names: VS-0145;Drug: Docetaxel<br>* 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<br>* Other names: Taxotere;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response rate | The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Measured with RECIST v 1.1 | with response evaluations performed every 3 cycles (each cycle is 28 days), up to 3 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival (OS) is defined as the time from registration to death due to any cause, or censored at date last known alive | up to 3 years | 
| Progression Free Survival (PFS) | Progression-Free Survival (PFS) is 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. | Up to 3 years | 
| Duration of therapeutic response | The duration of overall response is 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, or death due to any cause. Participants without events reported are censored at the last disease evaluation). | Up to 3 years | 
| Number of Participants with treatment related Adverse Events per CTCAE 5.0 | NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | Up to 3 Years | 
| The EORTC QOL Module for Head and Neck Cancer (QLQC30) |  | screening, after completion of a 5-7 day lead-in phase of duvelisib prior to cycle 1, every 3 cycles (each cycle is 28 days), and at 30-day follow-up up to 3 years | 
| The EORTC QOL Module for Head and Neck Cancer ( HN35) |  | screening, after completion of a 5-7 day lead-in phase of duvelisib prior to cycle 1, every 3 cycles (each cycle is 28 days), and at 30-day follow-up up to 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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