Impact of Selective Radiation Dose Escalation and Tumour Hypoxia Status on Locoregional Tumour Control After Radiochemotherapy of HNT

NCT01212354 | Unknown Phase 3 DMC

• 1 other identifier: ESC-928-MOL-0000-I
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief Summary

The major clinical problem and predominant cause of death after radio-oncological treatment of H+N cancers are loco-regional relapses. This randomized trial tests the hypothesis that dose escalated Intensity Modulated Radiotherapy (IMRT) selectively applied to the macroscopic primary tumor and involved neck nodes - which both in 80% - are hypoxic improves loco-regional control by at least 15% at 2 years. IMRT is combined with concurrent Cis-Platin chemotherapy. Tumor volume which correlates with number of malignant cells as well as tumor hypoxia are important biological parameters which increase radio-resistance, failure of local control and tumor progression. Basing on data of experimental and clinical radiation oncology we consider hypoxia as a useful parameter for pre-therapeutic strati-fication in future randomized radio-chemotherapy trials. In addition, hypoxia imaging by PET can be used for testing the significance of selective dose escalation on hypoxic tumor sub-volumes ("Dose Painting"). As a prerequisite for such innovative studies addressing hypoxia the translational part investigates the following key issues: correlation between the size of total tumor volume (primary, lymph nodes) and hypoxic sub-volume, the spatial shift of the hypoxic sub-volume before start of treatment and the correlation of loco-regional control and hypoxia. Before starting the main study a pre-study to assess the occurrence of radiation induced toxicities is mandatory to be performed. In a step-wise dose-escalation in a cohort-design the safety of dose-escalation should be determined. Step one: 6 patients Step two: 14 patients. In the pre-study the 1st group (6 patients) should be treated with 2.2 Gy up to 77.0 Gy for DEVPT and DEVLK. After evaluation of the toxicity the next 14 patients should be treated by this scheme.

Conditions

Locally Advanced Head and Neck Cancer

Keywords

intensity modulated radiotherapy; selective dose escalation; hypoxia; head cancer; neck cancer

Outcome Measures

Primary Outcomes (1)

• 2 year-loco-regional control

  2 years

Secondary Outcomes (9)

• Overall Survival (OS)

  2 years

• Progression-free survival (PFS)

  2 years

• Time to progression (TTP)

  5 years

• Distant metastases (DM)

  2 years

• Acute and late toxicity esp. concerning salivary glands

  5 years

Study Arms (2)

A - experimental

EXPERIMENTAL

7 weeks Radiotherapy Intervention with with 5x2.3 Gy per week up to a total dose of 80.5 Gy and parallel chemotherapy of 20 mg/m²/d Cisplatin in week 1 and 5.

Radiation: Radiotherapy

B - control

ACTIVE COMPARATOR

7 weeks Radiotherapy Intervention with 5x2.0 Gy per week up to a total dose of 70 Gy and parallel chemotherapy of 20 mg/m²/d Cisplatin in week 1 and 5.

Radiation: Radiotherapy

Interventions

Radiotherapy RADIATION

7 weeks Radiation dose escalation (5 x 2.3 Gy up to 80.5 Gy total dose)

Also known as: IMRT-SIB

A - experimental; B - control

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Age ≥ 18 ≤ 70 years
• Independent of gender
• Independent of race
• ECOG 0 - 2
• Tumor of oral cavity, oropharynx or hypopharynx
• Histology: squamous cell carcinoma
• Curative treatment intended
• Tumor is classified as irresectable (see Appendix)
• Woman of child-bearing age: negative pregnancy test in serum
• Contraception in male and female patients and their partners if of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post therapy
• all patients should have a dental examination before starting therapy and when necessary be treated, adaptation of a teeth protection bar
• a percutane feeding tube should be applied before start of treatment

You may not qualify if:

• Infiltration of the mandible and / or larynx
• impaired renal and/ or liver function
• secondary malignancy, unknown primary cancer, nasopharynx cancer or salivary gland cancers
• Metastatic disease
• Another cancer within 5 years of study entry
• Serious concomitant disease or medical condition
• Pregnancy or lactation
• Women of child-bearing potential with unclear contraception (post menopausal women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential)
• previous treatment with chemotherapy, radiotherapy or surgery in head and neck (except an excisional biopsy or biopsy for histology)
• concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening
• life expectancy of \< 12 months
• contraindications to receive Cisplatin
• social situations that limit compliance with study requirements

Sponsors & Collaborators

• Technical University of Munich: lead

Study Sites (1)

Klinik für RadioOnkologie Strahlentherapie

Munich, Bavaria, 81675, Germany

RECRUITING

Related Publications (2)

• Pigorsch SU, Kampfer S, Oechsner M, Mayinger MC, Mozes P, Devecka M, Kessel KK, Combs SE, Wilkens JJ. Report on planning comparison of VMAT, IMRT and helical tomotherapy for the ESCALOX-trial pre-study. Radiat Oncol. 2020 Nov 2;15(1):253. doi: 10.1186/s13014-020-01693-2.

  PMID: 33138837 DERIVED

• Pigorsch SU, Wilkens JJ, Kampfer S, Kehl V, Hapfelmeier A, Schlager C, Bier H, Schwaiger M, Combs SE. Do selective radiation dose escalation and tumour hypoxia status impact the loco-regional tumour control after radio-chemotherapy of head & neck tumours? The ESCALOX protocol. Radiat Oncol. 2017 Mar 1;12(1):45. doi: 10.1186/s13014-017-0776-1.

  PMID: 28249612 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Hypoxia

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Steffi U. Pigorsch, Dr. med.

  Klinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar der TU München Ismaningerstr. 22; 81675 Munich, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sabine Barta, Dr.

CONTACT

+49 (0)89-4140; sabine.barta@mri.tum.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2010
• First Posted: September 30, 2010
• Study Start: July 1, 2015
• Primary Completion: January 1, 2025
• Study Completion: September 1, 2025
• Last Updated: February 9, 2016

Record last verified: 2016-02

Locations

DE (1)