Study of a Pembrolizumab-based Organ Preservation Strategy for Locally Advanced Larynx Cancers

NCT04943445 | Active Not Recruiting Phase 2

• 1 other identifier: LACOG 0720
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 10

Brief Summary

This a prospective, single-arm, multi-institutional, open label, phase 2 trial evaluating the effects of induction chemo-immunotherapy, followed by radioimmunotherapy, followed by consolidation immunotherapy in patients with locally advanced squamous cell carcinoma of the larynx who are candidates for organ preservation.

Conditions

Squamous Cell Carcinoma of Larynx

Outcome Measures

Primary Outcomes (1)

• Two-year laryngectomy-free survival

  The primary efficacy endpoint is the two-year laryngectomy-free survival of patients with locally advanced larynx cancers treated with the study regimen. This endpoint combines assessment of both survival and larynx preservation and was used in the pivotal RTOG 91-11 study (12, 14), thus allowing for comparison with a historical control.

  24 months

Secondary Outcomes (1)

• Two-year larynx dysfunction-free survival

  24 months

Study Arms (1)

Treatment: Single Arm

EXPERIMENTAL

Induction chemo-immunotherapy: Carboplatin AUC of 6, paclitaxel 175 mg/m2, and pembrolizumab 200 mg, i.v. on day 1, every 21 days for 3 cycles. Patients without disease progression will proceed to the concurrent radioimmunotherapy phase of the trial. Concurrent radio-immunotherapy: Radiation therapy given concurrently with pembrolizumab 200 mg i.v. on day 1, every 21 days for 3 cycles. Patients without disease progression will proceed to the consolidation immunotherapy phase of the trial. Consolidation immunotherapy: Pembrolizumab 200 mg i.v. on day 1, every 21 days for 11 doses.

Drug: carboplatin AUC of 6, paclitaxel 175 mg/m2, and pembrolizumab 200 mg, i.v. on day 1, every 21 days for 3 cycles; Radiation: Concurrent radio-immunotherapy: radiation therapy given concurrently with pembrolizumab 200 mg i.v. on day 1, every 21 days for 3 cycles.; Drug: Consolidation immunotherapy: pembrolizumab 200 mg i.v. on day 1, every 21 days for 11 doses.

Interventions

carboplatin AUC of 6, paclitaxel 175 mg/m2, and pembrolizumab 200 mg, i.v. on day 1, every 21 days for 3 cycles DRUG

Patients without disease progression will proceed to the concurrent radioimmunotherapy phase of the trial.

Treatment: Single Arm

Concurrent radio-immunotherapy: radiation therapy given concurrently with pembrolizumab 200 mg i.v. on day 1, every 21 days for 3 cycles. RADIATION

Patients without disease progression will proceed to the consolidation immunotherapy phase of the trial.

Treatment: Single Arm

Consolidation immunotherapy: pembrolizumab 200 mg i.v. on day 1, every 21 days for 11 doses. DRUG

Consolidation immunotherapy

Treatment: Single Arm

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age on the day of signing informed consent
• Histologically or cytologically confirmed new diagnosis of squamous cell carcinoma of the larynx (glottic or supraglottic).
• Stages III, IVA, or IVB according to the AJCC (American Joint Cancer Committee) staging manual, 8th edition
• Male participants:
• A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• If available, provision of an archived tumor tissue block (or at least 20 newly cut unstained slides) where such samples exist in a quantity sufficient to allow for analysis. A recent (≤3 months) tumor biopsy prior to treatment initiation is an optional requirement, provided that a biopsy procedure is technically feasible, and the procedure is not associated with unacceptable clinical risk. For patients without an available archival sample and who decline a new biopsy prior to study entry, enrolment without tissue provision will be allowed.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Have adequate organ function

You may not qualify if:

• Large volume T4 disease, defined as invasion through the cartilage or extension \> 1 cm to the base of the tongue
• T1 disease, defined as tumor limited to one subsite of the supraglottis or limited to the vocal cords, with normal vocal-cord mobility, according to the TNM staging system.
• Contra indication, in the opinion of the treating physician, for radiotherapy, carboplatin or paclitaxel.
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment initiation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
• a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• b Creatinine clearance (CrCl) should be calculated per institutional standard. Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
• Has received any prior systemic anti-cancer therapy for management of the participant's current cancer, including investigational agents prior to allocation.
• Has received prior radiotherapy to the neck
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine.
• Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent with anti-cancer activity or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
• Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers

Sponsors & Collaborators

• Latin American Cooperative Oncology Group: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

CRIO - Centro Regional Integrado de Oncologia

Fortaleza, Ceará, 60.335-480, Brazil

Location

Liga Norte Riograndense Contra o Câncer

Natal, Rio Grande do Norte, 59.062-000, Brazil

Location

CPO - Centro de Pesquisa em Oncologia do Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, 90.610-000, Brazil

Location

Hospital de Amor de Barretos

Barretos, São Paulo, 14.784-400, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP

Ribeirão Preto, São Paulo, 14.015-010, Brazil

Location

FUNFARME - Hospital de Base de São José do Rio Preto

São José do Rio Preto, São Paulo, 15.090-000, Brazil

Location

INCA - Instituto Nacional de Câncer

Rio de Janeiro, 20.230-130, Brazil

Location

ICESP - Instituto do Câncer do Estado de São Paulo

São Paulo, 01.246-000, Brazil

Location

BP - A Beneficência Portuguesa de São Paulo

São Paulo, 01.323-030, Brazil

Location

A.C. Camargo Cancer Center

São Paulo, 01.509-001, Brazil

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Paclitaxel; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

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

Study Officials

• William Nassib William Junior

  Latin American Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: June 29, 2021
• Study Start: February 22, 2022
• Primary Completion: October 16, 2025
• Study Completion: October 16, 2025
• Last Updated: February 13, 2025

Record last verified: 2025-02

Locations

BR (10)