A clinical research study comparing two cisplatin dosing schedules combined with radiation for patients with advanced head and neck cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cancer Trials Ireland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Jan 2025 → ongoing

Decision date (initial)

2024-10-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

NRG Oncology

External identifiers

EU CT number

2024-515237-15-00

EudraCT number

2022-004130-19

ClinicalTrials.gov

NCT05050162

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others, Therapy, Pharmacogenetic

Phase II:
> To determine whether radiation with cisplatin weekly is superior in
terms of acute toxicity, as measured by the T-scores (TAME method), to
radiation with cisplatin every 3 weeks for patients with locoregionally
advanced squamous cell carcinoma of the head and neck (SCCHN).

Phase III:
> To determine whether radiation with cisplatin weekly is non-inferior to
radiation with cisplatin every 3 weeks in terms of overall survival (OS)
for patients with locoregionally advanced SCCHN.
> To determine whether radiation with cisplatin weekly is superior in
terms of acute toxicity, as measured by the T-scores (TAME method), to
radiation with cisplatin every 3 weeks for patients with locoregionally
advanced SCCHN.

Secondary objectives 9

1. To assess and compare progression-free survival (PFS) between arms.
2. To assess and compare locoregional failure and distant metastasis between arms.
3. To assess acute and late toxicity (CTCAE v5.0).
4. To assess patient-reported outcomes quality of life (PRO/QOL), as measured by the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) (primary PRO), between arms.
5. To assess hearing loss, as measured by audiograms and the modified TUNE grading scale between arms
6. To assess hearing loss, as measured by speech audiometry Consonant- Nucleus-Consonant word scores and tympanometry
7. To assess hearing-related QOL as measured by the Hearing Handicap Inventory-Screening (HHIA-S) (secondary PRO), between arms.
8. To assess long-term PFS, OS, and toxicity between arms.
9. To assess 3-year restricted-mean survival time for OS & PFS between arms (if long-term update is warranted).

Conditions and MedDRA coding

Advanced head and neck cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the head and neck (SCCHN) of the oropharynx, larynx, hypopharynx, or p16-positive unknown primary.
2. Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations.
3. Clinical stage (AJCC, 8th ed.) as indicated in the trial protocol, including no distant metastases based diagnostic workup.
4. Age ≥ 18;
5. Zubrod (ECOG) performance status of 0-1 within 14 days prior to registration;
6. Adequate hematologic function within 30 days prior to registration defined in the trial protocol.
7. Adequate renal function within 30 days prior to registration (per protocol definition).
8. Adequate hepatic function within 30 days prior to registration defined as follows: • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (not applicable to patients with known Gilbert's syndrome); • AST and ALT ≤ 1.5 x institutional ULN.
9. Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and CD4 T Cell count > 200 cells/mm3 are eligible for this trial. Testing is not required for entry into protocol.
10. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
11. Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration.
12. Willing to use highly effective contraceptives for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 14 months (females); for 11 months (males) following last dose of cisplatin.
13. The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.

Exclusion criteria 8

1. Patients with oral cavity cancer, nasopharynx cancer, or p16-negative cancer of unknown primary (CUP);
2. Recurrence of the study cancer;
3. Definitive clinical or radiologic evidence of distant metastatic disease;
4. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable, however, any prior exposure to cisplatin is excluded;
5. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
6. Severe, active co-morbidity defined as follows: • Unstable angina requiring hospitalization in the last 6 months; • Myocardial infarction within the last 6 months; • New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.); • Persistent Grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be reversed despite replacement as indicated by repeat testing; • Patient must not have an active infection requiring IV antibiotics prior to registration; • Other chronic renal disease like nephrotic syndrome, that could be worsened by cisplatin therapy; • History of allogenic organ transplantation; • Any symptomatic peripheral sensory neuropathy Grade ≥ 2 (CTCAE version 5.0);
7. Pregnancy and individuals unwilling to discontinue nursing.
8. 8 History of hypersensitivity to cisplatin or platinum-containing compounds.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase II Primary Endpoint: Acute toxicity, as measured by the T-scores.
2. Phase III Primary Endpoints: • Primary: Overall Survival (OS).
3. Co-primary: Acute toxicity, as measured by the T-scores.

Secondary endpoints 11

1. Locoregional failure.
2. Distant metastasis.
3. Progression-Free Survival (PFS).
4. 3-year restricted mean survival time (RMST) for OS and PFS (if longterm update is warranted).
5. Acute toxicity, as measured by CTCAE v5.0.
6. Late toxicity, as measured by CTCAE v5.0.
7. Late toxicity, as measure by the A-scores.
8. Quality of life, as measured by FACT-H&N.
9. Hearing loss, as measured by HHIA-S.
10. Hearing loss (cochleotoxicity), as measured by audiograms and the modified TUNE grading scale.
11. Speech audiometry Consonant-Nucleus-Consonant word scores and tympanometry (subject to the modified TUNE grading scale testing results; otherwise, it will be an exploratory endpoint).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cancer Trials Ireland

Sponsor organisation

Cancer Trials Ireland

Address

Rcsi House, 121 Saint Stephen's Green 121 Saint Stephen's Green

City

Dublin 2

Postcode

D02 H903

Country

Ireland

Scientific contact point

Organisation

Cancer Trials Ireland

Contact name

Head of clinical Operations

Public contact point

Organisation

Cancer Trials Ireland

Contact name

Head of clinical Operations

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications