Temozolomide Combine With Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost for Non Small Cell Lung Cancer Brain Metastases

A Phase II/III Study of Non Small Cell Lung Cancer Patient With/Without Synchronous Oral Temozolomide Capsules Combine With Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost With Hippocampus Protection

With the improvement of systemic therapeutic effect(especially in the population with driver gene mutation), the incidence of brain metastases had significantly increased. Conventional Whole Brain radiotherapy(WBRT) was less effective, the stereotactic radiosurgery(SRS) technique had improve the local efficacy for 1-3 lesions, but the probability of intracranial recurrence was increased, Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost(SIB-IMRT) is a new radiotherapy technology, Giving a standard radiation dose of whole brain ,at the same time can boost the high-risk region in target, So that it can significantly shorten the treatment time, at the same time can improve the local control rate of brain metastases. In the aspect of normal tissue protecting, SIB was better than WBRT plus SRS sequential treatment pattern. 30Gy to the whole brain had a negative effects on cognitive function, the investigators previous study found that 25Gy to the whole brain while the tumor bed Simultaneous push to 50Gy was safe and effective, while reducing the impact on cognitive function. Hippocampus is a part of the brain located in the temporal lobe, Mainly responsible for long-term memory storage conversion and orientation. Many investigators point out that hippocampus is the main commander of neurocognitive function, Reduce the dose of hippocampus can significant improve the neurocognitive function. Temozolomide capsule is an anti-tumor alkylation agent for glioblastoma multiforme and anaplastic astrocytoma. In recent years, some researchers find that Temozolomide capsules combine with radiotherapy such as SRS, WBRT or The two combined, can improve Objective response(OR) and prolong the Progress Free Survival(PFS),while with tolerable therapeutic toxicity. In order to better reduce the impact on cognitive function and improve the local control rate, the investigators present this trial, under the SIB-IMRT technique, the investigators want to explore the effect of temozolomide in brain metastasis of non-small cell lung cancer with the hippocampal protection technology.

Study Overview

• Status: Unknown
• Conditions: Non Small Cell Lung Cancer Metastatic
• Intervention / Treatment: Device: radiotherapy; Drug: Temozolomide capsules

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 2; Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have an estimated survival of at least 4 weeks
2. Karnofsky Performance Status Scale (KPS) of 60-100.
3. Patients' laboratory values had to meet these restrictions: hemoglobin>8 g/dL, platelets>70*109/L, white blood cells>4*109/L.
4. Patients must sign a study specific informed consent form prior to study entry

Exclusion Criteria:

1. Patients had major medical illnesses or psychiatric impairments which will prevent completion of the protocol therapy
2. had received previous brain irradiation
3. could not be regularly followed
4. with leptomeningeal involvement

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: RT groups; participants was given radiotherapy only,50Gy in 10 fractions over 2 weeks to metastases synchronously with 25Gy WBRT	Device: radiotherapy; Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost
Experimental: Drug plus RT groups; Temozolomide capsules(Jiangsu tasly diyi pharmaceutical Co.,Ltd) Oral Temozolomide capsules 75mg/m2 begins on day 1 and continues until completion of radiotherapy.	Drug: Temozolomide capsules; Temozolomide capsules(Jiangsu tasly diyi pharmaceutical Co.,Ltd) Oral Temozolomide capsules 75mg/m2 begins on day 1 and continues until completion of radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	overall survival	Duration of time from the start of therapy 3 years or until time of death, whichever occurs first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
iPFS	intracranial Progress Free Survival	Duration of time from the start of therapy to the time of intracranial disease progression, assessed up to 3 years
MMSE scores	mini mental state examination,The MMSE scores included 11 questions and was consisted of orientation to time (5 scores), orientation to place (5 scores), registration (3 scores), attention and calculation (5 scores), recall (3 scores), langue (2 scores), repetition (1 scores), complex commands (6 scores). The minimum score was 0, The maximum score was 30.	up to 2 years
overall response rate	use RECIST 1.1 version	Up to 1 month

Collaborators and Investigators

• Sponsor: Taizhou Hospital
• Investigators: Principal Investigator: Jian Zhu, MD, Taizhou Hospital, Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2019
• Primary Completion (Anticipated): January 31, 2022
• Study Completion (Anticipated): May 30, 2022

Study Registration Dates

• First Submitted: November 2, 2018
• First Submitted That Met QC Criteria: November 4, 2018
• First Posted (Actual): November 6, 2018

Study Record Updates

• Last Update Posted (Actual): January 29, 2019
• Last Update Submitted That Met QC Criteria: January 28, 2019
• Last Verified: January 1, 2019

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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: YHH-201807

Drug and device information, study documents

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