- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04193293
A Study of Duvelisib in Combination With Pembrolizumab in Head and Neck Cancer
A Phase 1b/2 Study of Duvelisib in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Head and Neck Squamous Cell Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- UPMC Hillman Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria
- Eastern Cooperative Oncology Group performance status ≤ 1
- Histologically or cytologically confirmed diagnosis of recurrent or metastatic head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx that was considered incurable by local therapies
- Eligible for pembrolizumab monotherapy based on the current prescribing information for pembrolizumab (Keytruda 2019)
- Must have had 0 to 2 prior therapies for R/M HNSCC
- At least 1 measurable lesion (which has not been previously irradiated) according to Response Evaluation Criteria in Solid Tumors version 1.1
- For stage 1 only: Must have had at least 1 other lesion that could be biopsied and willing to undergo a pretreatment and on-treatment biopsy of the available tumor lesion
- For stage 1 only: Must have been willing to undergo a pretreatment and on-treatment biopsy of the available tumor lesion
Adequate organ function defined by the following laboratory parameters:
- Absolute neutrophil count ≥ 1.5 × 10^9/liter (L)
- Platelet count ≥ 100 × 10^9/L
- Hemoglobin level ≥ 9.0 grams/deciliter (dL)
- A serum creatinine level < 1.5 milligrams/dL, or
- Estimated creatinine clearance value ≥ 60 milliliters/minute (as determined by the Cockcroft-Gault method) for participants with creatinine levels > 1.5 × institutional upper limit of normal (ULN)
- Total bilirubin level ≤ 1.5 × ULN (exception: participants with Gilbert's Syndrome may have a bilirubin level > 1.5 × ULN)
- Aspartate aminotransaminase/serum glutamic-oxaloacetic transaminase and alanine aminotransferase/serum pyruvic transaminase levels ≤ 2.5 × ULN or ≤ 5 × ULN in participants with liver metastases
- International normalized ratio or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN, unless participant was receiving anticoagulant therapy in which case PT or aPTT must have been within therapeutic range of intended use of anticoagulants
Exclusion Criteria
- Previously treated with 3 or more systemic regimens given for recurrent and/or metastatic disease
- Received anticancer treatment, major surgery, or any investigational drug within 30 days or 5 half-lives, whichever is shorter, before the start of study intervention
- Received radiation therapy within 14 days before the start of study intervention, including, in addition (if necessary), the timeframe for resolution of any actual or anticipated toxicities from such radiation; Palliative radiation is allowed if > 7 days and any toxicity is ≤ Grade 1
- Previous treatment with a PI3K, PD-1 or programmed cell death ligand 1 inhibitor
- Have received organ or allogenic bone marrow or peripheral blood stem cell transplant
- History of drug-induced colitis or drug-induced pneumonitis; history or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function; tuberculosis treatment within 2 years prior to the start of study intervention; chronic liver disease or veno-occlusive disease/sinusoidal obstruction syndrome
- Active cytomegalovirus or Epstein-Barr virus infection; history of or known human immunodeficiency virus infection
- Ongoing treatment with chronic immunosuppressants or systemic steroids or treatment for systemic bacterial, fungal, or viral infection
- Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
- Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A. No prior use within 2 weeks before the start of study intervention Received a live or live attenuated vaccine within 6 weeks of first dose of duvelisib
- Unable to receive prophylactic treatment for pneumocystis, HSV, or VZV at screening
- Any active gastrointestinal dysfunction interfering with the participant's ability to be administered oral medications
- Known active central nervous system metastases and/or carcinomatous meningitis
- QT interval > 500 milliseconds (except for participants with a right or left bundle branch block)
- New York Heart Association Class III or IV congestive heart failure
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Duvelisib + Pembrolizumab
Stage 1: Duvelisib twice daily (BID) for 1 week followed by combination therapy with duvelisib BID + pembrolizumab every 3 weeks (q3w) (Cycle 1 was 4 weeks consisting of the 1-week duvelisib monotherapy lead-in period followed by 1 dose of pembrolizumab in combination with 3 additional weeks of continuous dosing of duvelisib; subsequent cycles were 3 weeks). Stage 2: Duvelisib BID + pembrolizumab q3w in 3-week cycles. |
Phosphoinositide 3-kinase (PI3K) Inhibitor
Other Names:
Immunotherapy (programmed cell death protein 1 [PD-1] inhibitor)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Stage 1: Number of Participants With Dose-limiting Toxicities
Time Frame: 4 weeks or 28 days
|
4 weeks or 28 days
|
|
Stage 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame: 6 months
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Number of participants with TEAEs as assessed by the Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) as a measure of safety and tolerability of duvelisib in combination with pembrolizumab.
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6 months
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Stage 1 and 2: Overall Response Rate (ORR)
Time Frame: Up to 2 years
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Proportion of participants achieving complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1).
|
Up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Stage 1: ORR
Time Frame: Until documented progressive disease (PD), unacceptable toxicity, discontinuation criteria are met, withdrawal, or death (up to 2 years)
|
Proportion of participants achieving complete CR or PR according to RECIST v 1.1.
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Until documented progressive disease (PD), unacceptable toxicity, discontinuation criteria are met, withdrawal, or death (up to 2 years)
|
Stage 1 and 2: Duration of Response (DOR)
Time Frame: From first response until documented PD (up to 2 years)
|
Time from response ≥ PR to documented disease progression according to RECIST v 1.1.
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From first response until documented PD (up to 2 years)
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Stage 1 and 2: Progression-free Survival (PFS)
Time Frame: From start of treatment until documented PD or death (up to 2.5 years)
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Time from start of treatment to documented disease progression according to RECIST v 1.1, or death due to any cause.
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From start of treatment until documented PD or death (up to 2.5 years)
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Stage 1 and 2: Overall Survival
Time Frame: From start of treatment until death (up to 2.5 years)
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Time from start of treatment to death.
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From start of treatment until death (up to 2.5 years)
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Stage 1 and 2: Maximum Observed Concentration [Cmax]
Time Frame: Up to 5 cycles (46 weeks)
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Pharmacokinetics (PK) parameters for duvelisib (and metabolite IPI-656) determined using bioanalytical data and Population PK (POPPK) modeling.
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Up to 5 cycles (46 weeks)
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Stage 1 and 2: Area Under the Curve [AUC]
Time Frame: Up to 5 cycles (46 weeks)
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PK parameters for duvelisib (and metabolite IPI-656) determined using bioanalytical data and POPPK modeling.
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Up to 5 cycles (46 weeks)
|
Stage 1 and 2: Number of Participants With TEAEs
Time Frame: 24 months
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Number of participants with TEAEs as assessed by CTCAE v5.0.
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24 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Head and Neck Neoplasms
- Neoplasms, Squamous Cell
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Pembrolizumab
- Immune Checkpoint Inhibitors
Other Study ID Numbers
- VS-0145-130
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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