Dose Escalation Versus Standard in Laryngopharyngeal Cancers

NCT02757222 | Completed DMC

• 1 other identifier: EC/TMC/38/14
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (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

  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 Outcomes (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.

  2 years

Study Arms (2)

Standard dose

ACTIVE COMPARATOR

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

Escalated dose

EXPERIMENTAL

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

Interventions

Escalated Dose RADIATION

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.

Escalated dose

Standard Dose RADIATION

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.

Standard dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Tata Medical Center: lead

Study Sites (1)

Tata Medical Centre

Kolkata, West Bengal, 700156, India

Location

Related Publications (8)

• 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.

  PMID: 16101334 BACKGROUND

• 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.

  PMID: 20530316 BACKGROUND

• 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.

  PMID: 22101580 BACKGROUND

• 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 locally advanced head and neck cancer. Radiother Oncol. 2007 Oct;85(1):36-41. doi: 10.1016/j.radonc.2007.07.011. Epub 2007 Aug 20.

  PMID: 17709149 RESULT

• 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: DAHANCA 6 and 7 randomised controlled trial. Lancet. 2003 Sep 20;362(9388):933-40. doi: 10.1016/s0140-6736(03)14361-9.

  PMID: 14511925 RESULT

• 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 standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys. 2000 Aug 1;48(1):7-16. doi: 10.1016/s0360-3016(00)00663-5.

  PMID: 10924966 RESULT

• 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 a simultaneous integrated boost (SIB) approach. Radiother Oncol. 2013 Mar;106(3):333-40. doi: 10.1016/j.radonc.2013.03.002. Epub 2013 Mar 27.

  PMID: 23541643 RESULT

• 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. Epub 2012 Feb 9.

  PMID: 22319013 RESULT

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Laryngeal Neoplasms; Hypopharyngeal Neoplasms

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms

Study Officials

• Sanjoy Chatterjee, FRCP, FRCR

  Tata Medical Center: Kolkata

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: It is a radiation dose escalation study.

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: May 2, 2016
• Study Start: January 1, 2016
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: December 28, 2023

Record last verified: 2023-12

Locations

IN (1)