Dose Escalation/De-escalation Study of Pre-operative Stereotactic Radiosurgery for Brain Metastases(RAD 1002) (RAD 1002)

RAD 1002: Phase I Dose Escalation/De-escalation Study of Pre-operative Stereotactic Radiosurgery for Brain Metastases

This study will investigate the safety, tolerability, and effectiveness of changing the order of receiving radiation therapy for treating brain cancer. The investigators hope that changing the sequence of radiation therapy will lower the risk of cancer spreading throughout your spinal fluid, which covers your brain and spinal cord.

Study Overview

• Status: Completed
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: Stereotactic Radiosurgery (15 Gy); Radiation: Stereotactic Radiosurgery (12 Gy)

Detailed Description

This study will attempt to determine the maximum tolerated dose of pre-operative stereotactic radiosurgery (SRS) in the treatment of brain metastases. Patients will be placed in one of two dose groups based on index tumor size, and dose will be adjusted according to presence or absence of dose limiting toxicity (DLT).

Group A: Index Tumor > 2 cm and up to 4 cm in maximum diameter Group B: Index Tumor > 4 cm and up to 6 cm in maximum diameter

Dose escalation or de-escalation will be conducted via a modified 3+3 method at the following levels. Group A will start at dose level II. Group B will start at dose level I.

Dose Level I: 12 Gy Dose Level II: 15 Gy

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Hazelrig-Salter Radiation Oncology Center/University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All subjects must have history of histologically confirmed malignancy. Brain biopsy is not required unless diagnosis is judged to be in doubt by the treating physician.
• Newly diagnosed brain metastases (four or fewer by post-contrast MRI obtained within six weeks of study entry)
• At least one brain metastasis (index tumor) must be within 2-6 cm in maximum diameter and deemed appropriate for surgical resection by the treating neurosurgeon.
• Karnofsky performance status (KPS) of greater than or equal to 60
• Age greater than 19
• Life expectancy greater than 12 weeks
• Subjects given written informed consent

Exclusion Criteria:

• Patients with small cell lung cancer and lymphoma are ineligible.
• More than four metastases by baseline post-contrast MRI
• Prior whole brain radiation therapy
• Insufficient recovery from all active toxicities of prior therapies
• Subjects who are deemed to be poor surgical risks by the treating neurosurgeon because of medical comorbidities
• Pregnant or nursing women
• Women of childbearing potential who are not using an effective method of contraception are excluded. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to administration of SRS.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Stereotactic Radiosurgery (15 Gy); Group A: If the tumor which will be surgically removed is at least 2 cm and up to 4 cm in maximum diameter, then this group will receive Dose Level II (15 Gy) of radiation: stereotactic radiosurgery (SRS) followed by surgery to remove the tumor.	Radiation: Stereotactic Radiosurgery (15 Gy); Group A will start at dose level II: 15 Gy Group B will start at dose level I: 12 Gy
EXPERIMENTAL: Stereotactic Radiosurgery (12Gy); Group B: If the tumor which will be surgically removed is larger than 4 cm and up to 6 cm in diameter, then this group will receive Dose Level I (12 Gy) of radiation: stereotactic radiosurgery (SRS) followed by surgery to remove the tumor.	Radiation: Stereotactic Radiosurgery (12 Gy); Group B will start at Dose Level I: 12 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum tolerated dose (MTD) of preoperative stereotactic radiosurgery (SRS) for brain metastasis	The maximum tolerated dose (MTD) is defined as the highest dose of stereotactic radiosurgery delivered pre-operative at which no more than 2 out of 6 patients experience a dose limiting toxicity (DLT).	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Toxicity with preoperative stereotactic radiosurgery (SRS)	Any possible, probable, or definite treatment-related AE or SAE (assessed by CTCAE 4.0) occurring within six months or less from the date of stereotactic radiosurgery was received.	6 months
Late Toxicity with preoperative stereotactic radiosurgery (SRS)	Any possible, probable, or definite treatment-related AE or SAE (assessed by CTCAE 4.0) occurring more than six months from the date of stereotactic radiosurgery was received.	1 year
Rates of Local Control	This will be assessed by MRI Imaging obtained post-operatively at follow-up visits.	2 years
Rates of Leptomeningeal Dissemination	Leptomeningeal Dissemination (LMD) defined as diffuse carcinomatosis and/or distant focal pachymeningeal (dural) tumor and assessed by MRI Imaging for the study period.	2 years

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: John B. Fiveash, MD, Hazelrig-Salter Radiation Oncology Center (HSROC)/ University of Alabama at Birmingham (UAB)

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ACTUAL): November 1, 2016
• Study Completion (ACTUAL): April 1, 2018

Study Registration Dates

• First Submitted: November 22, 2010
• First Submitted That Met QC Criteria: December 2, 2010
• First Posted (ESTIMATE): December 3, 2010

Study Record Updates

• Last Update Posted (ACTUAL): May 14, 2018
• Last Update Submitted That Met QC Criteria: May 10, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: brain metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: F100528006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No