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Dose Escalation Versus Standard in Laryngopharyngeal Cancers (INTELHOPE)

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ClinicalTrials.gov Identifier: NCT02757222
Recruitment Status : Recruiting
First Posted : May 2, 2016
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Dr. Sanjoy Chatterjee, Tata Medical Center

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Malignant Neoplasm of Oropharynx Stage III Malignant Neoplasm of Larynx Stage III Malignant Neoplasm of Hypopharynx Stage III Malignant Neoplasm of Oropharynx Stage IVa Malignant Neoplasm of Oropharynx Stage IVb Malignant Neoplasm of Larynx Stage IV Malignant Neoplasm of Hypopharynx Stage IVa Malignant Neoplasm of Hypopharynx Stage IVb Radiation: Escalated Dose Radiation: Standard Dose Phase 1 Phase 2

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  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intensifying Radiation Treatment in Advanced/ Poor Prognosis Laryngeal, Hypopharyngeal (LH) and Oropharyngeal Cancers (OPC) Using PET -CT Based Dose Escalation Strategies ( INTELHOPE)
Study Start Date : January 2016
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


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.





Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02757222


Contacts
Contact: Sanjoy Chatterjee, FRCP,FRCR 03366057101 sanjoy.chatterjee@tmckolkata.com
Contact: Indranil Mallick, MD 03366057103

Locations
India
Tata Medical Centre Recruiting
Kolkata, West Bengal, India, 700156
Contact: Sanjoy Chatterjee, MRCP,FRCR    9038161825    sanjoy.chatterjee@tmckolkata.com   
Sponsors and Collaborators
Tata Medical Center
Investigators
Principal Investigator: Sanjoy Chatterjee, FRCP, FRCR Tata Medical Center: Kolkata

Publications of Results:

Other Publications:
Responsible Party: Dr. Sanjoy Chatterjee, Senior Consultant Clinical Oncologist, Tata Medical Center
ClinicalTrials.gov Identifier: NCT02757222     History of Changes
Other Study ID Numbers: EC/TMC/38/14
First Posted: May 2, 2016    Key Record Dates
Last Update Posted: April 17, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Once appropriate authorities approach and once clearance of local authorities is received, data could be shared

Additional relevant MeSH terms:
Neoplasms
Laryngeal Diseases
Oropharyngeal Neoplasms
Hypopharyngeal Neoplasms
Laryngeal Neoplasms
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Respiratory Tract Neoplasms