Hypoxia-guided Radiotherapy With Cisplatin-etoposide in Stage I-III : Small Cell Lung Cancer(SCLC) (HX4 in SCLC)

Individualized Hypoxia-guided Radiotherapy Combined With Standard Cisplatin-etoposide in Stage I-III SCLC

Since radiation dose escalation to a large volume of tumour inevitably will induce higher toxicity than is currently the case, efforts must be made to limit the volume of tissue irradiated. Moreover, the irradiation of larger tumour volumes leads to a lower achievable tumour dose when keeping the normal tissue doses constant. Central is thus the question whether it would be possible to limit the volume of tumour to be boosted by selectively escalating the radiation dose to specific disease sites which are theoretically more prone to relapse.

Study Overview

• Status: Withdrawn
• Conditions: Small Cell Lung Cancer (SCLC)
• Intervention / Treatment: Drug: [18F]HX4

Detailed Description

Hypoxic imaging with PET scans seems attractive for this purpose as hypoxia is associated with resistance for radiotherapy and approximately 70 % of SCLC are severely hypoxic at diagnosis[2].

We hypothesize that it might be possible to use a selective boost in these patients to tumor areas which are still hypoxic at the end of the standard chemo-radiotherapy to a dose of 45 Gy in 30 fractions in 3 weeks.

This way all SCLC (small cell lung cancer) patients can receive a safe, but higher dose of radiotherapy to the whole tumor volume, while the most resistant areas receive the highest possible dose.

This is a hypothesis generating trial designed to deliver at least the current standard treatment to malignant tissue while defining patient selection criteria for future study.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed stage I-III small cell lung cancer. WHO performance status 0-2
• Absolute neutrophil count at least 1800/µl and platelets at least 100000/µl and hemoglobin at least 6.2 mmol/l.
• Adequate renal function: calculated creatinine clearance at least 40 ml/min
• Adequate hepatic function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution; ALT, AST, and alkaline phosphatase ≤ 2.5 x ULN for the institution (in case of liver metastases ≤ 5 x ULN for the institution)
• No previous platinum chemotherapy or topo-isomerase-inhibitors for SCLC.
• Lung function: FEV1 at least 30 % and DLCO at least 30 % of the age predicted value
• No history of prior chest radiotherapy
• Life expectancy more than 6 months
• Willing and able to comply with the study prescriptions
• 18 years or older
• Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study
• Ability to give and having given written informed consent before patient registration
• No mixed pathology, e.g. non-small cell plus small cell cancer
• No recent (< 3 months) severe cardiac disease (NYHA class >1) (congestive heart failure, infarction)
• No uncontrolled infectious disease
• No other active malignancy
• No major surgery (excluding diagnostic procedures like e.g. mediastinoscopy) in previous 4 weeks
• No treatment with investigational drugs in 4 weeks prior to or during this study

Exclusion Criteria:

• The opposite of the above

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [18F]HX4	Drug: [18F]HX4; Intravenous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative local progression 18 months post-treatment as evaluated in a chest FDG-PET-CT scan	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival at two years	2 years

Collaborators and Investigators

• Sponsor: Maastricht Radiation Oncology
• Collaborators: Maastricht University Medical Center
• Investigators: Principal Investigator: Dirk De Ruysscher, MD, PhD, Maastro Clinic, The Netherlands

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Anticipated): January 1, 2014
• Study Completion (Anticipated): August 1, 2014

Study Registration Dates

• First Submitted: September 21, 2010
• First Submitted That Met QC Criteria: September 27, 2010
• First Posted (Estimate): September 28, 2010

Study Record Updates

• Last Update Posted (Estimate): August 27, 2013
• Last Update Submitted That Met QC Criteria: August 26, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Progression; Survival; Toxicity; SCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Signs and Symptoms, Respiratory; Lung Neoplasms; Small Cell Lung Carcinoma; Hypoxia
• Other Study ID Numbers: HX4 in small cell lung cancer; 2010-023033-30 (EudraCT Number)