Phase I Dose Escalation in Patients With 1-3 Unresectable Brain Metastases

NCT02080949 | Withdrawn Phase 1 DMC

• 1 other identifier: HSRT
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Brain metastases occur in 20-40% of patients with metastatic cancer. The standard treatment is based on whole brain radiation therapy and local treatment of metastases as neurosurgery or radiosurgery. However, many cases can not receive a standard local treatment, and local relapse occurs in almost 50% of cases treated with only whole brain irradiation. There are retrospective studies of increased radiation dose at the site of metastasis with hypofractionated stereotactic radiotherapy (HSRT) with favorable results, but there are no controlled studies regarding the safety of radiation dose in these situations. This study is a phase I study to evaluate the maximum tolerance dose (MTD) with HSRT as a way to increase the dose of radiation after the WBRT for patients with 1-3 brain metastases not eligible for surgery or RS.

Conditions

Brain Metastases

Keywords

brain metastases, hypofractionated stereotactic radiotherapy

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerance Dose

  To establish the MTD with HSRT as a way to increase the dose of radiation after the WBRT for patients with 1-3 brain metastases not eligible for surgery or RS, and find the dose for phase II study.

  Always after 3 patients recruited (up to 30 days after completion of radiotherapy planned)

Secondary Outcomes (2)

• Radiotoxicity

  Up to 30 days after the end of radiotherapy

• Neurocognitive benefit

  Baseline and up to 30 days after completion of radiotherapy planned

Study Arms (1)

HSRT - 4fx x 5 Gy

EXPERIMENTAL

It'll be recruited 3 patients to the initial regimen of four fractions of 5 Gy on each brain metastasis with HSRT and if no patient has unacceptable toxicity, more 3 patients for subsequent scheme will be recruited. If 2 patients had unacceptable toxicity, the study ends and it'll be considered that the study was initiated with toxic regimen. If 1 patient has unacceptable toxicity, it'll be recruited 3 more patients for this scheme and if 1 or more patients had unacceptable toxicity, the scheme will be considered toxic and the study will be closed. If no patient develops unacceptable toxicity, the study will follow to the next cohort of 3 more patients with the next dose level.

Radiation: 4fx x 5Gy

Interventions

4fx x 5Gy RADIATION

It'll be recruited 3 patients to the initial scheme of 4 fractions of 5 Gy on each brain metastasis with HSRT and if no patient has unacceptable toxicity, more 3 patients for subsequent scheme will be recruited. If 2 patients had unacceptable toxicity, the study ends and it'll be considered the study initiated with toxic regimen. If 1 patient has unacceptable toxicity, it'll be recruited 3 more patients for this scheme and if 1 or more patients had unacceptable toxicity, the scheme will be considered toxic and the study will be closed. If no patient develops unacceptable toxicity, the study will follow to the next cohort of 3 more patients with next dose level. The same criteria of recruitment will be performed till any scheme reach the MTD or up to the scheme of 4 fractions of 9 Gy.

Also known as: hypofractionated stereotactic radiotherapy

HSRT - 4fx x 5 Gy

Eligibility Criteria

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

You may qualify if:

• Patients with 1-3 brain metastases with histological diagnosis of malignancy and ineligible for surgery or RS
• Age ≥18 years
• Karnofsky Performance Status (KPS) ≥ 70%
• "Status" of neurological function: zero to 3
• Anticipated survival \> 3 months
• Informed consent for this research signed

You may not qualify if:

• Prior brain irradiation for any reason
• Indian race
• Primary tumor of lymphoma, leukemia, germ cell, small cell carcinoma or central nervous system
• Leptomeningeal dissemination
• single or multiple metastases with surgical (patients with KPS ≥ 70, with metastatic site in an area not eloquent or herniation causing mass effect or hydrocephalus) or RS indication(patients with KPS ≥ 70 and metastatic lesion \<4 cm in diameter with distance to chiasm, tract and optic nerves, and brain stem \> 5 mm)
• Inability to have MRI
• Patients who have undergone prior treatment for specific brain metastases (eg surgery, RS, chemotherapy), excluding corticosteroids
• People with mental incapacity
• People in a relationship of dependence as prisoners, soldiers, students, staff, etc..

Sponsors & Collaborators

• Barretos Cancer Hospital: lead

Study Sites (1)

Barretos Cancer Hospital - Fundação Pio XII

Barretos, São Paulo, 14784-400, Brazil

Location

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Ricardo A Nakamura, MD

  Barretos Cancer Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2014
• First Posted: March 7, 2014
• Study Start: January 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: March 7, 2014

Record last verified: 2014-03

Locations

BR (1)