Pulsed Dose Chemotherapy Plus Pembrolizumab in Recurrent/Metastatic HNSCC

NCT06052839 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 23-071
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The rationale for the new sequence of pulsed dose chemotherapy proposed in this trial is based on the hypotheses that current standard dosing of chemotherapy plus pembrolizumab ultimately suppresses the immune system and has a negative effect on the efficacy of the anti-PD-1 monoclonal antibody (mAb) therapy and that chemotherapy given after anti-PD-1 mAb therapy is associated with higher efficacy.

Conditions

Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

Keywords

CD8 tumor infiltrating lymphocyte (TIL); interferon gamma (IFNγ); anti-PD-1 mAb

Outcome Measures

Primary Outcomes (1)

• 6-month Progression-free Survival (PFS)

  Proportion of patients alive and without disease progression at 6 months after starting treatment, per RECIST v1.1. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

  At 6 months

Secondary Outcomes (4)

• Adverse Events (AE) and Serious Adverse Events (SAE) Related to Treatment

  Up to 2 years

• Overall Response Rate (ORR)

  Up to 2 years

• Duration of Response (DOR)

  Up to 4 years

• Overall Survival (OS)

  Up to 4 years

Study Arms (1)

Pembrolizumab + Carboplatin with Paclitaxel

EXPERIMENTAL

Pembrolizumab: Administer 200 mg intravenously (IV) every 3 weeks (q3w); maintenance will be continued at 400 mg IV q6w for 12 cycles for a total of 2 years of therapy Carboplatin: Started with cycle 2 (C2) of pembrolizumab and continued thereafter every 3rd cycle of pembrolizumab for a total of 4 cycles with paclitaxel; carboplatin will be given at C2, C5, C8, and C11 of pembrolizumab. Paclitaxel: Started with cycle 2 (C2) of pembrolizumab and continued thereafter every 3rd cycle of pembrolizumab for a total of 4 cycles with carboplatin.

Drug: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Pembrolizumab DRUG

Immunotherapy that works by helping the immune system to kill cancer cells by targeting and blocking a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells.

Also known as: Keytruda®

Pembrolizumab + Carboplatin with Paclitaxel

Carboplatin DRUG

A chemotherapy drug that contains the metal platinum. It stops or slows the growth of cancer cells and other rapidly growing cells by damaging their DNA.

Pembrolizumab + Carboplatin with Paclitaxel

Paclitaxel DRUG

A chemotherapeutic agent used as a treatment for various cancers; paclitaxel is a mitotic inhibitor.

Also known as: Taxol

Pembrolizumab + Carboplatin with Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent/metastatic squamous cell carcinoma of the head and neck that is considered incurable by local therapies.
• PD-L1 Combined Positive Score (CPS) \>1
• Age \> 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) 0-2
• Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) 1
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤ 1.5 X the institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN (≤ 5 X the institutional ULN for patients with liver metastasis)
• Creatinine clearance ≥40 mL/min/1.73 m2 for patients with a creatinine levels above institutional normal.
• Female subjects of childbearing potential should have a negative urine or serum pregnancy during the screening period and also prior to receiving the first dose of study medication. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use one methods of birth control or abstain from heterosexual activity for the course of the study through 60 days after the last dose of study medication. Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 60 days after the last dose of study therapy.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients should not have had prior systemic therapy alone administered in the recurrent/ or metastatic setting. If a patient received platinum based systemic therapy which was completed more than 6 months prior to signing consent given as part of multimodal curative intent treatment for locally advanced HNSCC (This includes both definitive concurrent chemoradiation and adjuvant chemoradiation) the patient is still eligible,
• A patient cannot have received prior anti-PD-1 or anti-PD-L1 monoclonal antibody (mAb) therapy as systemic therapy for the treatment of recurrent/metastatic disease. Patients that received anti-PD-1 or anti-PD-L1 mAb therapy as part of multimodality curative intent treatment of locally advanced disease are still eligible as long as it has been at least 1 year since prior therapy. Patients that received anti-PD-1 or anti-PD-L1 mAb therapy as part of radiation for locoregional recurrence will be eligible as long as it has been 1 year since prior therapy.
• Squamous cell carcinoma of the skin or of salivary gland origin.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months, or a syndrome that requires ongoing systemic steroids or immunosuppressive agents. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism or Sjogren's syndrome will not be excluded from the study.
• Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis.
• Prior malignancy within 2 years that in the investigator's opinion would be likely to affect the outcomes of the patients R/M HNSCC.
• Peripheral sensory neuropathy \> grade 2 by CTCAE v5.0
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Known allergy or hypersensitivity to carboplatin, other platinum agents, pembrolizumab, or paclitaxel.
• Baseline neutrophil count of \< 1,500 cells/mm.

Sponsors & Collaborators

• Dan Zandberg: lead

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

pembrolizumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Dan P Zandberg, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Ruth, RN, BSN

CONTACT

412-623-8963; ruthj2@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine / Medical oncologist/hematologist

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: September 25, 2023
• Study Start: October 3, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)