Dose Escalation Versus Standard in Laryngopharyngeal Cancers (INTELHOPE)

December 21, 2023 updated by: Tata Medical Center

Intensifying Radiation Treatment in Advanced/ Poor Prognosis Laryngeal, Hypopharyngeal (LH) and Oropharyngeal Cancers (OPC) Using PET -CT Based Dose Escalation Strategies ( INTELHOPE)

The primary objective of the study is to establish the safety of using a moderate escalation of radiotherapy dose in advanced/poor prognosis OPC and LH cancers receiving curative radiotherapy.

The study will also explore the efficacy (improvement in complete response rates at 2 years) of dose escalation in intermediate and high risk OPC and LH cancers patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients with locally advanced Laryngeal, Hypopharyngeal (LH) or oropharyngeal (OPC) head and neck squamous cell carcinomas have 5 year survival ranging between 25-45%. 60% of all LH cancers occur in the developing world and its incidence in India ranges from 1.8-8.8 per 1,00,000 population .

Local control outcomes of OPC patients with stage III and IV OPC has been modest with reported loco-regional control rates of 50-60% at 5 years. For patients with locally advanced LH a 60-70% 2 year survival is seen and loco-regional control rates of 70% have been reported . Majority of locally advanced OPC and LH cancers are treated with a combination of chemotherapy and radiotherapy (CRT) with organ and function preserving approach.

Identifying the area of tumour involvement in the OPC and LH could be challenging on CECT scans, requiring metabolic imaging with PET-CT for more precise definition of radiation target.

Improvements in radiation treatment delivery techniques have enabled clinicians to explore the possibility of improving tumour control probability (TCP) and reduce normal tissue complication probability . This allows us to explore the role of escalating dose in the above group of patients to assess the safety and efficacy of the regime.

Tumours treated in the standard dose arm will receive radiotherapy @ 220 cGy per fraction for 30 fractions whilst those in the escalated dose arm will receive @ 245 cGy per fraction for 30 fractions using IMRT techniques. Patients in both arms will receive weekly platinum based chemotherapy concurrent with radiotherapy.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Indranil Mallick, MD
  • Phone Number: 03366057103

Study Locations

  • India
    • West Bengal
      • Kolkata, West Bengal, India, 700156
        • Tata Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

LH Inclusion Criteria ALL of the following inclusion criteria must be met

  • Histologically confirmed squamous cell cancer of the larynx or hypopharynx
  • Radiotherapy with concomitant chemotherapy as primary therapy
  • Induction chemotherapy is permitted
  • TNM Stage T3-4, N0-3, M0 or T1/2 with N2-3 disease (Stage III or IV a/b) disease
  • WHO performance status of 0 or 1
  • Creatinine clearance of more than 50ml/min
  • All patients must be suitable to attend regular follow up

OPC inclusion criteria ALL of the following inclusion criteria must be met

  • Histologically confirmed squamous cell cancer of the oropharynx
  • Radiotherapy with concomitant chemotherapy as primary therapy
  • Induction chemotherapy is permitted
  • WHO performance status of 0 or 1
  • Creatinine clearance of more than 50ml/min
  • All patients must be suitable to attend regular follow up
  • And any of the stage of disease as seen below HPV (p16) negative: TNM Stage T2-T4, any N stage, M0 disease HPV (p16) Positive: more than 10 pack year history and N2b or N3 disease

LH Exclusion Criteria The patient is ineligible if ANYONE of the following exclusion criteria is met

  • Previous radiotherapy to the head and neck region
  • Previous malignancy except non-melanoma skin cancer and early stage cancer in remission for at least 5 years following treatment
  • Previous or concurrent illness, which in the investigator's opinion would interfere with either completion of therapy or follow-up
  • Pre-existing previous speech or swallowing problems unrelated to the diagnosis of cancer
  • Patients with locally advanced LH tumours where organ preservation is unrealistic
  • Patients with metastatic carcinoma

OPC Exclusion Criteria The patient is ineligible if ANYONE of the following exclusion criteria is met

  • Previous radiotherapy to the head and neck region
  • Previous malignancy except non-melanoma skin cancer and early stage cancer in remission for at least 5 years following treatment
  • Previous or concurrent illness, which in the investigator's opinion would interfere with either completion of therapy or follow-up
  • Pre-existing previous speech or swallowing problems unrelated to the diagnosis of cancer
  • Patients with locally advanced LH or OPC tumours where organ preservation is unrealistic
  • Patients with metastatic carcinoma
  • Low risk OPC: HPV p16 positive T1-2 with N0-N2a disease or less than 10 pack year history

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard dose
Patients receive a radiation dose of 66Gy in 30 fractions to the planning target volume 1 (PTV1) and 54 Gy in 30 fractions to the PTV2 concurrent with platinum chemotherapy weekly
Radiation: Standard Dose

CTV 1 includes 6mm isotropic margin around the entire PET-CT avid (thresholding at 40% of SUV max) larynx/ hypopharynx /oropharynx and 5mm isotropic margin around nodes.

CTV 2: This (CTV 2) includes the area around the primary or nodal levels at risk of harbouring microscopic primary or microscopic nodal involvement, or at risk nodal areas, and not already included in CTV1.

Planning Target Volume: PTV - A margin of 5mm will be added to each of the CTV to obtain the PTV.

PTV 1 receives 66Gy in 30 fractions. PTV 2 receives 54 Gy in 30 fractions.

All patients receive concurrent platinum chemotherapy.
Experimental: Escalated dose
Patients receive a radiation dose of 73.5 Gy in 30 fractions to the boost target volume (BTV), 63Gy in 30 fractions to PTV1 and 54 Gy in 30 fractions to PTV2 concurrent with platinum chemotherapy weekly
Radiation: Escalated Dose

Boost Target Volume (BTV): The PET CT GTV (thresholding at 40% of SUV max) with a 3mm margin will form the BTV.

CTV1: A 3mm area around the BTV avid primary or 2mm area around the node will form the CTV1.

CTV 2: This (CTV 2) includes the area around the primary or nodal levels at risk of harbouring microscopic primary or microscopic nodal metastatic disease and not already included in CTV1.

Planning Target Volume: PTV - A margin of 5mm will be added to each of the CTV to obtain the PTV.

BTV receives 73.5Gy in 30 fractions. PTV 1 receives 63Gy in 30 fractions. PTV 2 receives 54 Gy in 30 fractions.

All patients receive concurrent platinum chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with Grade 3 through grade 5 adverse events that are related to dose escalation, graded according to NCI CTCAE version 4.0
Time Frame: 2 years
In addition: Interim assessment for early stoppage is if 35% or more patients in the intervention arm has Grade 4 mucositis or dysphagia
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Efficacy (improvement in complete response rates at 2 years) of dose escalation in intermediate and high risk Oropharyngeal cancer (OPC) patients and in node positive, locally advanced Laryngeal and Hypopharyngeal cancer patients.
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tata Medical Center

Investigators

  • Principal Investigator: Sanjoy Chatterjee, FRCP, FRCR, Tata Medical Center: Kolkata

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (Actual)

December 1, 2022

Study Completion (Actual)

December 1, 2022

Study Registration Dates

First Submitted

March 22, 2016

First Submitted That Met QC Criteria

April 27, 2016

First Posted (Estimated)

May 2, 2016

Study Record Updates

Last Update Posted (Actual)

December 28, 2023

Last Update Submitted That Met QC Criteria

December 21, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EC/TMC/38/14

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Once appropriate authorities approach and once clearance of local authorities is received, data could be shared

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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