Clinical trial NCT01252797: Dose Escalation/De-escalation Study of Pre-operative Stereotactic Radiosurgery for Brain Metastases(RAD 1002)
Official title: RAD 1002: Phase I Dose Escalation/De-escalation Study of Pre-operative Stereotactic Radiosurgery for Brain Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain Metastases
Keywords: brain metastases
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2010-12-03
Enrollment: 20
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: maximum tolerated dose (MTD) of preoperative stereotactic radiosurgery (SRS) for brain metastasis
timeFrame: one year
Secondary outcomes:
measure: Acute Toxicity with preoperative stereotactic radiosurgery (SRS)
timeFrame: 6 months
measure: Late Toxicity with preoperative stereotactic radiosurgery (SRS)
timeFrame: 1 year
measure: Rates of Local Control
timeFrame: 2 years
measure: Rates of Leptomeningeal Dissemination
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Hazelrig-Salter Radiation Oncology Center/University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: Hazelrig-Salter Radiation Oncology Center (HSROC)/ University of Alabama at Birmingham (UAB)
name: John B. Fiveash, MD
role: PRINCIPAL_INVESTIGATOR
References: