Dose escalation of Stereotactic Radiosurgery for brain metastases

A Phase I Dose-Escalation Study of Stereotactic Radiosurgery for Brain Metastasis Without Whole Brain Radiation

This study is testing whether giving higher doses of Stereotactic Radiosurgery can help people with brain metastases feel better and live longer compared to standard doses.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 135 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Texas Southwestern Medical Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Dallas, Texas)
• Trial ID: NCT02645487 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of increasing doses of Stereotactic Radiosurgery (SRS) on patients with brain metastases who have not previously received radiation treatment. The goal is to determine the maximum tolerable doses that could improve local tumor control, survival rates, and quality of life. By focusing on patients with limited brain metastases, the study aims to enhance treatment outcomes compared to the current standard doses established by previous guidelines. The research will involve careful monitoring of patients' responses to the escalated doses over time.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with biopsy-proven non-hematopoietic malignancies and 10 or fewer brain metastases, each measuring 3.0 cm or less.

Not a fit: Patients with small cell lung cancer, germ cell cancer, or unknown primary tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to better long-term control of brain metastases and improved survival for patients.

How similar studies have performed: Other studies have indicated that dose escalation in SRS may improve outcomes, suggesting this approach has potential based on prior findings.

Eligibility criteria

Inclusion Criteria

1. Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
2. Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
3. All brain metastases must be outside the brain stem (midbrain, pons and medulla).
4. Patient must have 10 or less brain metastases.
5. The maximum diameter of any lesion must be less than or equal to 3.0 cm.
6. Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:

   * Radiation was not to the brain.
   * Surgery to the brain was \> 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
7. Age ≥ 18 years.
8. ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
9. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

   A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
   * Has not undergone a hysterectomy or bilateral oophorectomy; or
   * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
10. Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

1. Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
2. Patients with leptomeningeal metastasis.

   NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
3. Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
4. Patients with life expectancy \< 3 months.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
6. Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Where this trial is running

Dallas, Texas

• University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Robert Timmerman, MD — Utsw
• Study coordinator: Jonathan VanPelt, MHA

Conditions Brain Neoplasms, Adult, Malignant