AzTrials
AzTrials

Squamous Cell Carcinoma of LarynxPhase 2SMART-KEYNCT04943445

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

A Phase 2 study testing carboplatin AUC of 6, paclitaxel 175 mg/m2, and pembrolizumab 200 mg, i.v. on day 1, every 21 days for 3 cycles, Concurrent radio-immunotherapy: radiation therapy given concurrently with pembrolizumab 200 mg i.v. on day 1, every 21 days for 3 cycles. and Consolidation immunotherapy: pembrolizumab 200 mg i.v. on day 1, every 21 days for 11 doses. in people with Squamous Cell Carcinoma of Larynx, run by Latin American Cooperative Oncology Group at 9 sites in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Squamous Cell Carcinoma of Larynx
What is being tested?
carboplatin AUC of 6, paclitaxel 175 mg/m2, and pembrolizumab 200 mg, i.v. on day 1, every 21 days for 3 cycles, Concurrent radio-immunotherapy: radiation therapy given concurrently with pembrolizumab 200 mg i.v. on day 1, every 21 days for 3 cycles. and Consolidation immunotherapy: pembrolizumab 200 mg i.v. on day 1, every 21 days for 11 doses.
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
9 sitesBrazil
Study dates
22 Feb 2022to 28 Aug 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 13Show fewer
  • 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

Who cannot join

  • 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.
Show all 27Show fewer
  • 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
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab, carboplatin, paclitaxel and/or any of their excipients.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA qualitative detected) infection.
  • Note: no testing for Hepatitis B and Hepatitis C is required
  • Has known active TB (Bacillus Tuberculosis).
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
  • Has had an allogenic tissue/solid organ transplant.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Brazil9 sites

  • Hospital de Amor de Barretos

    Barretos, São Paulo, 14.784-400

  • CRIO - Centro Regional Integrado de Oncologia

    Fortaleza, Ceará, 60.335-480

  • Liga Norte Riograndense Contra o Câncer

    Natal, Rio Grande do Norte, 59.062-000

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

    Porto Alegre, Rio Grande do Sul, 90.610-000

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

    Ribeirão Preto, São Paulo, 14.015-010

  • FUNFARME - Hospital de Base de São José do Rio Preto

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

  • ICESP - Instituto do Câncer do Estado de São Paulo

    São Paulo, São Paulo, 01.246-000

  • A.C. Camargo Cancer Center

    São Paulo, São Paulo, 01.509-001

  • BP - A Beneficência Portuguesa de São Paulo

    São Paulo, São Paulo, 01323-030

Other trials in Brazil

About this study

Official title: A Single-arm, Multi-institutional, Phase 2 Study of a Pembrolizumab-based Organ Preservation Strategy for Locally Advanced Larynx Cancers

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.

Being tested
carboplatin AUC of 6, paclitaxel 175 mg/m2, and pembrolizumab 200 mg, i.v. on day 1, every 21 days for 3 cycles, Concurrent radio-immunotherapy: radiation therapy given concurrently with pembrolizumab 200 mg i.v. on day 1, every 21 days for 3 cycles., Consolidation immunotherapy: pembrolizumab 200 mg i.v. on day 1, every 21 days for 11 doses.
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    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.Radiation

    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

    Consolidation immunotherapy

Study groups in NCT04943445
Study groupRoleWhat they receive
Treatment: Single ArmExperimentalInduction 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.
Receives: 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 24 months

Secondary outcomes (1)

  1. Two-year larynx dysfunction-free survival

    The secondary efficacy endpoint is two-year larynx dysfunction-free survival, which is a composite endpoint defined as the proportion of patients alive and without local recurrence and without lanryngoesophageal dysfunction. This endpoint reflects the necessity of evaluating not only survival with the larynx in place, but also laryngeal function, as stated in the recommendations by an international consensus panel (24). This endpoint was evaluated in the pivotal GORTEC 2000-01 trial (25, 26), thus allowing for comparisons with a historical control. Larynx dysfunction-free survival is also the primary endpoint of the ongoing, randomized, phase 3 trial GORTEC 2014-03, which will become a benchmark for larynx preservation studies in the near future. Predictive biomarkers of response survival will be evaluated as exploratory analysis.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2021
  2. Study start22 Feb 2022
  3. Primary completion22 Aug 2023
  4. Study completion28 Aug 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04943445
Sponsor's protocol ID
LACOG 0720
Acronym
SMART-KEY
Status last verified
Aug 2026
First submitted
16 Jun 2021
Last updated
27 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing carboplatin AUC of 6, paclitaxel 175 mg/m2, and pembrolizumab 200 mg, i.v. on day 1, every 21 days for 3 cycles, Concurrent radio-immunotherapy: radiation therapy given concurrently with pembrolizumab 200 mg i.v. on day 1, every 21 days for 3 cycles. and Consolidation immunotherapy: pembrolizumab 200 mg i.v. on day 1, every 21 days for 11 doses. in people with Squamous Cell Carcinoma of Larynx, run by Latin American Cooperative Oncology Group at 9 sites in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Two-year laryngectomy-free survival (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04943445.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in