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Dose Escalation Versus Standard in Laryngopharyngeal Cancers (INTELHOPE)

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ClinicalTrials.gov Identifier: NCT02757222
Recruitment Status : Recruiting
First Posted : May 2, 2016
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Dr. Sanjoy Chatterjee, Tata Medical Center

March 22, 2016
May 2, 2016
April 17, 2018
January 2016
June 2018   (Final data collection date for primary outcome 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 [ Time Frame: 2 years ]
In addition: Interim assessment for early stoppage is if 35% or more patients in the intervention arm has Grade 4 mucositis or dysphagia
Same as current
Complete list of historical versions of study NCT02757222 on ClinicalTrials.gov Archive Site
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. [ Time Frame: 2 years ]
To explore the 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. [ Time Frame: 2 years ]
Not Provided
Not Provided
 
Dose Escalation Versus Standard in Laryngopharyngeal Cancers
Intensifying Radiation Treatment in Advanced/ Poor Prognosis Laryngeal, Hypopharyngeal (LH) and Oropharyngeal Cancers (OPC) Using PET -CT Based Dose Escalation Strategies ( INTELHOPE)

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
  • 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.

  • 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.

  • Active Comparator: 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
    Intervention: Radiation: Standard Dose
  • Experimental: 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
    Intervention: Radiation: Escalated Dose

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
Same as current
December 2020
June 2018   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Sanjoy Chatterjee, FRCP,FRCR 03366057101 sanjoy.chatterjee@tmckolkata.com
Contact: Indranil Mallick, MD 03366057103
India
 
 
NCT02757222
EC/TMC/38/14
Yes
Not Provided
Plan to Share IPD: Undecided
Plan Description: Once appropriate authorities approach and once clearance of local authorities is received, data could be shared
Dr. Sanjoy Chatterjee, Tata Medical Center
Tata Medical Center
Not Provided
Principal Investigator: Sanjoy Chatterjee, FRCP, FRCR Tata Medical Center: Kolkata
Tata Medical Center
April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP