a trial for treatment of cancer patients with multiple brain metastases undergoing whole-brain radiotherapy

Conditions: Multiple Brain Metastases

Summary: this protocol is for a lead-in safety study of 5 patients followed by a randomized phase 2 clinical trial of bmx-001, a new class of pharmaceutical, in 64 patients with multiple brain metastases (mbm) undergoing whole brain radiation therapy (wbrt). preliminary studies have demonstrated that bmx-001 provides protection of normal tissues from radiation-induced injury and augments tumor growth inhibition.

this protocol is for a phase 1 safety lead-in clinical trial of bmx-001 in combination with wbrt in 5 patients with mbm. demonstrating safety of the selected mtd of bmx-001 in patients with mbm undergoing standard protocol wbrt will be the "go/no-go" criteria for proceeding to phase 2. phase 2 is a randomized open-label phase 2 clinical trial of 64 patients with mbm, half receiving bmx-001 in combination with wbrt and half receiving wbrt alone. subjects are treated with bmx-001 for a total of 19 days, during which time they receive radiation therapy. following completion of radiation therapy, subjects will be followed for an additional one year.

Eligibility criteria:
inclusion criteria: * subjects must have histologically confirmed diagnosis of a non-small cell lung cancer, breast cancer, melanoma or renal cell cancer primary * subjects must have \>5 contrast-enhancing lesions, never previously treated with srs and/or surgical resection, on a contrast-enhanced t1-weighted brain mri performed within two weeks of enrollment, with at least one lesion \>0.5cm in greatest dimension * physical examination by a radiation oncologist or medical oncologist within 14 days of the start of wbrt * plan to be treated with wbrt to a dose of 30 gy in 10 fractions * age \* 18 years * karnofsky performance status (kps) ≥ 70 * hemoglobin ≥ 9.0 g/dl, anc ≥ 1,500 cells/\*l, platelets ≥ 125,000 cells/\*l * serum creatinine ≤ 1.5 mg/dl, serum sgot and bilirubin ≤ 1.5 times upper limit of normal * signed informed consent approved by the institutional review board * if sexually active, patients must agree to use appropriate contraceptive measures for the duration of the study and for 6 months afterwards as stated in the informed consent * able to provide study specific informed consent * willing to follow study procedures, complete qol questionnaires and neurocognitive testing as described in the protocol * negative serum pregnancy test for women of child bearing potential within 48 hours of first dose of bmx exclusion criteria: * active infection requiring iv antibiotics 7 days before enrollment * hypertension requiring 3 or more anti-hypertensive medications to control * requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precipitous decrease in blood pressure * history of syncope within the last 6 months * subjects receiving prohibited medications listed in section 6.4.2 of this protocol are not eligible. subjects who can safely stop taking a prohibited medication at least 7 days prior to the first dose of bmx may participate at the discretion of the treating physician. * pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic * women who are breast feeding * known hypersensitivity to compounds of similar chemical composition to bmx-001 * prior surgical resection for brain metastases and/or stereotactic radiosurgery for up to 5 brain metastases in total are permitted if performed at least 1 month prior to planned wbrt under this protocol. * prior whole brain radiation therapy * patients with diffuse leptomeningeal disease (carcinomatous meningitis) * a marked baseline prolongation of qt/qtc interval (e.g., repeated demonstration of a qtc interval \>480 milliseconds (ms) (ctcae grade 1) * a history of additional risk factors for tdp (e.g., congestive heart failure, hypokalemia, known family history of long qt syndrome)