PET/CT-directed Hyperfractionated Radiation Dose Escalation in Stage III Non-small Cell Lung Cancer

Phase I Study of PET/CT-directed Hyperfractionated Radiation Dose Escalation With Concurrent Weekly Carboplatin and Paclitaxel in Stage III Non-small Cell Lung Cancer

The goal of this study is to find the maximum tolerable dose of radiation that can be delivered combined with chemotherapy (carboplatin & paclitaxel) in patients with stage III non-small cell lung cancer (NSCLC).

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Radiation: radiochemotherapy 1; Radiation: radiochemotherapy 2; Radiation: radiochemotherapy 3; Radiation: radiochemotherapy 4; Radiation: radiochemotherapy 5; Radiation: radiochemotherapy 6; Radiation: radiochemotherapy 7

Detailed Description

Concurrent chemoradiotherapy is the standard of care for unresectable stage III NSCLC based on the results of phase III randomised trials. The current standard radiation therapy dose has remained 60- Gy at -2 Gy/fraction for nearly four decades (60Gy), with local disease control rates of approximately 50% and a median overall survival of only 18 months.These results are suboptimal and more effective treatment regimens are needed.

We hypothesize that hyperfractionated radiation dose escalation to residual tumor volumes after standard chemoradiotherapy as defined by positron emission tomography (PET) /computed tomography (CT) would improve local control and overall survival while reducing the acute and late normal tissue toxicity.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • the Ethic Committee of Shanghai General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have FDG-avid and histologically or cytologically proven non-small cell lung cancer.
2. Age 1 8-75.
3. Zubrod performance status 0-2.
4. Stage III ( American Joint Committee on Cancer AJCC, 7th ed.).
5. No prior radiation to the thorax that would overlap with the current treatment field.
6. Adequate bone marrow, renal and hepatic functions as assessed by the following: Hemoglobin >/= 10.0 g/dl, Platelet count >/= 1 00,000/mm^3,absolute granulocyte count (AGC) ≥2 × 10^9 cells/L,bilirubin and Aspartate transaminase ≤1.5 ×upper limit of normal (ULN), Creatinine </=1 .5 times ULN.
7. A signed informed consent must be obtained prior to therapy.
8. Induction chemotherapy is allowed.
9. Life expectancy more than 3 months.

Exclusion Criteria:

1. Patients with any component of small cell lung carcinoma are excluded from this study.
2. Patients with evidence of a malignant pleural or pericardial effusion are excluded.
3. Prior radiotherapy that would overlap the radiation fields.
4. Uncontrolled concurrent illness including, but not limited to: Chronic Obstructive Pulmonary Disease(COPD) exacerbation or other respiratory illness, serious uncontrolled infection, symptomatic congestive heart failure (CHF),unstable angina pectoris, uncontrolled hypertension,or psychiatric illness/social situations that would limit compliance with the study requirements.
5. Known hypersensitivity to paclitaxel.
6. Any other condition or circumstance that would, in the opinion of the Investigator, make the patient unsuitable for participation in the study.
7. Acquired Immune Deficiency Syndrome.
8. Conditions precluding medical follow-up and protocol compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: radiochemotherapy 1; Patients will be treated with radiation therapy 64.8 Gy	Radiation: radiochemotherapy 1; concurrent radiochemotherapy: radiotherapy dose level 1: 60 Gy at 2 Gy/Fx/d, then 4.8 Gy at 1.2 Gy/Fx/bid concurrent concurrent chemotherapy :carboplatin area under the curve (AUC) 2; paclitaxel: 45-50 mg/m2, weekly; Other Names: concurrent chemoradiotherapy regimen 1
Experimental: radiochemotherapy 2; Patients will be treated with radiation therapy 69.6 Gy	Radiation: radiochemotherapy 2; concurrent radiochemotherapy: radiotherapy dose level 2: 60 Gy at 2 Gy/Fx/d, then 9.6 Gy at 1.2 Gy/Fx/bid concurrent concurrent chemotherapy :carboplatin area under the curve (AUC) 2; paclitaxel: 45-50 mg/m2, weekly; Other Names: concurrent chemoradiotherapy regimen 2
Experimental: radiochemotherapy 3; Patients will be treated with radiation therapy 74.4 Gy	Radiation: radiochemotherapy 3; concurrent radiochemotherapy: radiotherapy dose level 3: 60 Gy at 2 Gy/Fx/d, then 14.4 Gy at 1.2 Gy/Fx/bid concurrent concurrent chemotherapy :carboplatin area under the curve (AUC) 2; paclitaxel: 45-50 mg/m2, weekly; Other Names: concurrent chemoradiotherapy regimen 3
Experimental: radiochemotherapy 4; Patients will be treated with radiation therapy 79.2 Gy	Radiation: radiochemotherapy 4; concurrent radiochemotherapy: radiotherapy dose level 4: 60 Gy at 2 Gy/Fx/d, then 19.2 Gy at 1.2 Gy/Fx/bid concurrent concurrent chemotherapy :carboplatin area under the curve (AUC) 2; paclitaxel: 45-50 mg/m2, weekly; Other Names: concurrent chemoradiotherapy regimen 4
Experimental: radiochemotherapy 5; Patients will be treated with radiation therapy 84 Gy	Radiation: radiochemotherapy 5; concurrent radiochemotherapy: radiotherapy dose level 5: 60 Gy at 2 Gy/Fx/d, then 4.8x5 Gy at 1.2 Gy/Fx/bid concurrent concurrent chemotherapy :carboplatin area under the curve (AUC) 2; paclitaxel: 45-50 mg/m2, weekly; Other Names: concurrent chemoradiotherapy regimen 5
Experimental: radiochemotherapy 6; Patients will be treated with radiation therapy 88.8 Gy	Radiation: radiochemotherapy 6; concurrent radiochemotherapy: radiotherapy dose level 6: 60 Gy at 2 Gy/Fx/d, then 4.8x6 Gy at 1.2 Gy/Fx/bid concurrent concurrent chemotherapy :carboplatin area under the curve (AUC) 2; paclitaxel: 45-50 mg/m2, weekly; Other Names: concurrent chemoradiotherapy regimen 6
Experimental: radiochemotherapy 7; Patients will be treated with radiation therapy 93.6 Gy	Radiation: radiochemotherapy 7; concurrent radiochemotherapy: radiotherapy dose level 7: 60 Gy at 2 Gy/Fx/d, then 4.8x7 Gy at 1.2 Gy/Fx/bid concurrent concurrent chemotherapy :carboplatin area under the curve (AUC) 2; paclitaxel: 45-50 mg/m2, weekly; Other Names: concurrent chemoradiotherapy regimen 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose	Maximum Tolerated Dose is defined as CTCAE 4 grade 3 acute radiation-related toxicity	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Local Failure	Local control will be assessed radiographically using endoscopy with biopsy and a positron emission computed tomography-CT scan	2 years

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: tingfeng chen, MD, the ethic committee of shanghai genernal hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2017
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: March 28, 2017
• First Submitted That Met QC Criteria: March 28, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Actual): May 3, 2019
• Last Update Submitted That Met QC Criteria: May 1, 2019
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: SGH201708

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No