Dose Escalation Versus Standard in Laryngopharyngeal Cancers

NCT ID: NCT02757222

Last Updated: 2023-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2022-12-31

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

It is a radiation dose escalation study.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Standard Dose

Intervention Type 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.

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

Group Type EXPERIMENTAL

Escalated Dose

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tata Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sanjoy Chatterjee, FRCP, FRCR

Role: PRINCIPAL_INVESTIGATOR

Tata Medical Center: Kolkata

Locations

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Tata Medical Centre

Kolkata, West Bengal, India

Site Status

Countries

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India

References

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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.

Reference Type BACKGROUND
PMID: 16101334 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20530316 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22101580 (View on PubMed)

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.

Reference Type RESULT
PMID: 17709149 (View on PubMed)

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.

Reference Type RESULT
PMID: 14511925 (View on PubMed)

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.

Reference Type RESULT
PMID: 10924966 (View on PubMed)

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.

Reference Type RESULT
PMID: 23541643 (View on PubMed)

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.

Reference Type RESULT
PMID: 22319013 (View on PubMed)

Other Identifiers

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EC/TMC/38/14

Identifier Type: -

Identifier Source: org_study_id