Induction Treatment in SCC of the Head and Neck Region - Concomitant Chemotherapy and Low-dose Radiotherapy (iCHRTL)

Induction Treatment in Patients With Squamous Cell Carcinoma (SCC) of the Head and Neck Region Consisting Concomitant Chemotherapy and Low-dose Ionizing Radiotherapy

Non-commercial clinical study to assess:

1. efficacy of iCHRTL in patients with advanced squamous cell carcinoma of oral cavity, pharynx carcinoma, larynx carcinoma or paranasal sinus carcinoma.
2. tolerability of iCHRTL in patients with advanced squamous cell carcinoma of oral cavity, pharynx carcinoma, larynx carcinoma or paranasal sinus carcinoma.
3. molecular and biochemical effect of low doses of ionizing radiation.

Study Overview

• Status: Recruiting
• Conditions: Paranasal Sinus Carcinoma; Squamous Cell Carcinoma of Oral Cavity; Larynx Carcinoma; Pharynx Carcinoma
• Intervention / Treatment: Other: Chemotherapy (carboplatin+paclitaxel) with concomitant low dose ionizing radiotherapy

Detailed Description

40 patients with squamous cell carcinoma of oral cavity, pharynx, larynx or paranasal sinuses in stage III or IV, previously not treated for this reason and eligible for induction chemotherapy.

Study treatment:

Induction phase:

Chemotherapy based on carboplatin 6 area under the curve (AUC) + paclitaxel 75 mg/m2 carboplatin 6 AUC 30-minute infusion on D: 1 (maximum carboplatin dose is 700 mg) paclitaxel 75 mg/m2 1-hour infusion on D: 1, 8, 15

Radiotherapy:

D:1 - 2 x 0,5 Gy (first dose up to one hour after the end of the carboplatin infusion, second dose 3 to 6 hours later), D:2 - 2 x 0,5 Gy (interval between doses not less than 3 hours), D:8 and D:15 - 2 x 0,5 Gy (first dose up to one hour after the end of the chemotherapeutic infusion, second dose 3 to 6 hours later).

2 cycles of induction treatment are planned. Interval between the last day of cycle I and the first day of cycle II is 7 days. After 2 weeks from second cycle Positron emission tomography (PET) and Magnetic Resonance (MR), medical case conference and qualification to further treatment: Radiotherapy (RT), Chemo-radiotherapy (CHRT) or other, depending on the medical decision.

Planned based on the optimal technique for a particular clinical case preferred: Intensity Modulated Radiation Therapy (IMRT). Preparation of IMRT plan will be based on computed tomography (CT) scans. Early tolerance of radiotherapy will be assessed for local reaction. At least once every 7 days.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tomasz Rutkowski, MD PhD; Phone Number: + 48 32 278 83 38; Email: tomasz.rutkowski@io.gliwice.pl
• Study Contact Backup: Name: Agnieszka Pietruszka, MD; Email: agnieszka.pietruszka@io.gliwice.pl

Study Locations

• Poland
  • Silesia
    • Gliwice, Silesia, Poland, 44-102
      • Recruiting
      • The Maria Sklodowska-Curie National Research Institute of Oncology, Branch in Gliwice
      • Contact: Tomasz Rutkowski, MD PhD; Phone Number: + 48 32 278 83 38; Email: tomasz.rutkowski@io.gliwice.pl
      • Contact: Agnieszka Pietruszka, MD; Email: agnieszka.pietruszka@io.gliwice.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with squamous cell carcinoma of oral cavity, upper, middle, lower pharynx carcinoma, larynx carcinoma or paranasal sinus carcinoma in advanced stage III or IV and previously not treated for this reason.
2. Severity of the disease: N1 > 2 cm, N2, N3 ; T2, T3, T4, M0
3. Patient eligible for radical treatment with induction chemotherapy (at least in good general condition (ZUBROD 0-1) with no significant additional diseases disqualifying from induction chemotherapy).
4. Written informed consent form to the proposed therapeutic scheme.
5. Age over 18 years.

Exclusion Criteria:

1. Subjects with known or suspected hypersensitivity to any of the study mediations.

2. Baseline values for the following parameters (in the screening phase):

   • Creatinine >2,0 x upper limit of normal (ULN) - unless creatinine clearance is normal
   • Total bilirubin >1,5 x ULN (except for hyperbilirubinemia caused by Gilbert's syndrome)
   • Alanine Transaminase (ALT) activity, Aspartate Transaminase (ASPAT) >2,5 x ULN
   • Alkaline phosphatase activity >2,5 x ULN
3. Prior treatment with any unauthorized medication or investigational treatment before the 5 half-lives of that substance or 4 weeks prior to study entry (a longer period of time should be assumed), or subjects currently enrolled to other interventional clinical trials.
4. Concomitant malignancy or history of a malignancy with a significant potential impact to tolerability or effectivity of iCHRTL.
5. Chronic or active infection requiring antibiotic, antifungal or antiviral treatment, such as, but not limited to: chronic kidney infection, chronic respiratory tract infection with bronchospasm, tuberculosis or active hepatitis C virus infection.
6. History of significant cerebrovascular disease within 6 months or currently symptomatic or its implications.
7. Human Immunodeficiency Virus (HIV) infection.
8. Clinically significant heart disease including unstable angina, myocardial infarction within 6 months prior to study entry, severe congestive circulatory failure class New York Heart Association (NYHA) III-IV, arrhythmias unless it is treated, except for collateral contractions or minimal conduction disorders.
9. Significant concomitant disease that cannot be treated, such as, but not limited to kidney, liver, gastrointestinal, endocrine system, respiratory, neurological and brain diseases and mental illnesses that may pose a risk to the patient in the opinion of the investigator.
10. Active hepatitis B virus (HBV) infection, defined as having a positive Hepatitis B surface antigen (HBsAg) test. Moreover, in case of a negative HBsAg test result but a positive Hepatitis B core Antibody (HBcAb) test result (regardless of HBsAb status), HBV DNA should be determined and in case of a positive result the patient cannot be included to the study.
11. Active hepatitis C virus (HCV) infection, defined as having a positive Hepatitis C Antibody (HCAb) test, in which case Hepatitis C virus recombinant immunoblot assay (HCV RIBA) should be determined from the same sample to confirm the result.
12. Pregnancy or breastfeeding (women of childbearing potential must have pregnancy test performed during screening).
13. Women of childbearing potential, including women whose last menstrual period occurred in less than one year before screening, who cannot or do not want to use adequate contraception methods from the beginning of the study until 6 months after the last dose of study drug. Adequate contraception is defines as the use of oral hormonal contraceptives, an intrauterine device, a double barrier method or sexual abstinence.
14. Men who cannot or do not want to use adequate contraception methods from the beginning of the study until 6 months after the last dose of study medication.
15. Patients who cannot or do not want to adhere to the study Protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Chemotherapy (Ch)+ Radiotherapy (RT); Induction phase: Chemotherapy based on carboplatin 6 AUC (area under the curve) + paclitaxel 75 mg/m2 carboplatin 6 AUC 30-minute infusion on D: 1 (maximum carboplatin dose is 700 mg) paclitaxel 75 mg/m2 1-hour infusion on D: 1, 8, 15 Radiotherapy: D:1 - 2 x 0,5 Gy (first dose up to one hour after the end of the carboplatin infusion, second dose 3 to 6 hours later), D:2 - 2 x 0,5 Gy (interval between doses not less than 3 hours), D:8 and D:15 - 2 x 0,5 Gy (first dose up to one hour after the end of the chemotherapeutic infusion, second dose 3 to 6 hours later).

Other: Chemotherapy (carboplatin+paclitaxel) with concomitant low dose ionizing radiotherapy; Chemotherapy based on carboplatin 6 AUC + paclitaxel 75 mg/m2. Radiotherapy: D:1 - 2 x 0,5 Gy (first dose up to one hour after the end of the carboplatin infusion, second dose 3 to 6 hours later), D:2 - 2 x 0,5 Gy (interval between doses not less than 3 hours), D:8 and D:15 - 2 x 0,5 Gy (first dose up to one hour after the end of the chemotherapeutic infusion, second dose 3 to 6 hours later).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) after induction	Complete+partial response in percent	1 year post-induction
Objective response rate (ORR) after induction	Complete+partial response in percent	3 years post-induction
Loco-regional control (LRC) rate	Rate of local lesions complete response (CR) +partial response (PR)+stable disease (SD)	1 year post-induction
Loco-regional control (LRC) rate	Rate of local lesions CR+PR+SD	3 years post-induction
Distant metastasis rate	Rate of patients with distant metastases	1 year post-induction
Distant metastasis rate	Rate of patients with distant metastases	3 years post-induction
Overall survival time (OS)	Rate of death within time from treatment start to 1 year	Date of treatment start - to 1 year
Overall survival time (OS)	Rate of death within time from treatment start to 3 years	Date of treatment start - to 3 years

Collaborators and Investigators

• Sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
• Collaborators: Medical Research Agency, Poland
• Investigators: Study Chair: Krzysztof Składowski, MD PhD, Maria Sklodowska-Curie National Research Institute of Oncology (MSCNRIO)

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2022
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: August 7, 2023
• First Posted (Actual): August 15, 2023

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: iCHRTL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No