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NCT02757222 Clinical Trial

Dose Escalation Versus Standard in Laryngopharyngeal Cancers

Malignant Neoplasm of Hypopharynx Stage III Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data
NCT number NCT02757222
Other study ID # EC/TMC/38/14
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date January 2016
Est. completion date December 2022

Study information
Verified date December 2023
Source Tata Medical Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility
Status Completed
Enrollment 100
Est. completion date December 2022
Est. primary completion date December 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design

Related Conditions & MeSH terms

Intervention

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.
• 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.

Locations
Country Name City State
India Tata Medical Centre Kolkata West Bengal

Sponsors (1)
Lead Sponsor Collaborator
Tata Medical Center

Country where clinical trial is conducted

India, 

References & Publications (8)

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. — View 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. — View Citation

Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, Garden AS, Ridge JA, Cooper JS, Ang KK. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to stand — View Citation

Guerrero Urbano T, Clark CH, Hansen VN, Adams EJ, A'Hern R, Miles EA, McNair H, Bidmead M, Warrington AP, Dearnaley DP, Harrington KJ, Nutting CM. A phase I study of dose-escalated chemoradiation with accelerated intensity modulated radiotherapy in locall — View 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. — View Citation

Leclerc M, Maingon P, Hamoir M, Dalban C, Calais G, Nuyts S, Serre A, Gregoire V. A dose escalation study with intensity modulated radiation therapy (IMRT) in T2N0, T2N1, T3N0 squamous cell carcinomas (SCC) of the oropharynx, larynx and hypopharynx using — View Citation

Overgaard J, Hansen HS, Specht L, Overgaard M, Grau C, Andersen E, Bentzen J, Bastholt L, Hansen O, Johansen J, Andersen L, Evensen JF. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAH — View Citation

Paleri V, Carding P, Chatterjee S, Kelly C, Wilson JA, Welch A, Drinnan M. Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: a prospective study. Head Neck. 2012 Dec;34(12):1747-52. doi: 10.1002/hed.22003. E — View Citation

Outcome
Type Measure Description Time frame Safety issue
Primary 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 2 years
Secondary 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. 2 years