Clinical trial NCT02757222: Dose Escalation Versus Standard in Laryngopharyngeal Cancers
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
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: Tata Medical Center
Sponsor class: OTHER
First posted: 2016-05-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: It is a radiation dose escalation study.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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
timeFrame: 2 years
Secondary outcomes:
measure: 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.
timeFrame: 2 years
Other outcomes:
Locations:
city: Kolkata
country: India
facility: Tata Medical Centre
state: West Bengal
Study officials:
affiliation: Tata Medical Center: Kolkata
name: Sanjoy Chatterjee, FRCP, FRCR
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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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 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.
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 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.
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. Epub 2012 Feb 9.