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Dose Escalation Versus Standard in Laryngopharyngeal Cancers (INTELHOPE)

Primary Purpose

Malignant Neoplasm of Oropharynx Stage III, Malignant Neoplasm of Larynx Stage III, Malignant Neoplasm of Hypopharynx Stage III

Status

Recruiting

Phase

Phase 1

Locations

India

Study Type

Interventional

Intervention

Escalated Dose

Standard Dose

About this trial

This is an interventional treatment trial for Malignant Neoplasm of Oropharynx Stage III

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Tata Medical CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard dose

Escalated dose

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

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

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.

Full Information

NCT ID

NCT02757222

First Posted

March 22, 2016

Last Updated

December 2, 2021

Sponsor

Tata Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT02757222

Brief Title

Dose Escalation Versus Standard in Laryngopharyngeal Cancers

Acronym

INTELHOPE

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 Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Recruiting

Study Start Date

January 2016 (undefined)

Primary Completion Date

December 2022 (Anticipated)

Study Completion Date

December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tata Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Standard dose

Arm Type

Active Comparator

Arm Description

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

Arm Title

Escalated dose

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Escalated Dose

Intervention Description

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.

Intervention Type

Radiation

Intervention Name(s)

Standard Dose

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

In addition: Interim assessment for early stoppage is if 35% or more patients in the intervention arm has Grade 4 mucositis or dysphagia

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sanjoy Chatterjee, FRCP,FRCR

Phone

03366057101

sanjoy.chatterjee@tmckolkata.com

First Name & Middle Initial & Last Name or Official Title & Degree

Indranil Mallick, MD

Phone

03366057103

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sanjoy Chatterjee, FRCP, FRCR

Organizational Affiliation

Tata Medical Center: Kolkata

Official's Role

Principal Investigator

Facility Information:

Facility Name

Tata Medical Centre

City

Kolkata

State/Province

West Bengal

ZIP/Postal Code

700156

Country

India

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sanjoy Chatterjee, MRCP,FRCR

Phone

9038161825

sanjoy.chatterjee@tmckolkata.com

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

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

Citations:

PubMed Identifier

16101334

Citation

Kapil U, Singh P, Bahadur S, Dwivedi SN, Singh R, Shukla N. Assessment of risk factors in laryngeal cancer in India: a case-control study. Asian Pac J Cancer Prev. 2005 Apr-Jun;6(2):202-7.

Results Reference

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PubMed Identifier

20530316

Citation

Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.

Results Reference

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PubMed Identifier

22101580

Citation

Chatterjee S, Willis N, Locks SM, Mott JH, Kelly CG. Dosimetric and radiobiological comparison of helical tomotherapy, forward-planned intensity-modulated radiotherapy and two-phase conformal plans for radical radiotherapy treatment of head and neck squamous cell carcinomas. Br J Radiol. 2011 Dec;84(1008):1083-90. doi: 10.1259/bjr/53812025.

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PubMed Identifier

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Citation

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Citation

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Dose Escalation Versus Standard in Laryngopharyngeal Cancers

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