Pharmacokinetics of Systemic Anti-Cancer Therapies in the Cerebrospinal Fluid (CSF) of Patients With Advanced Cancer

Very little is known about the penetration of systemic therapies through the normal blood
brain barrier and the ways in which a brain metastasis or radiation would impact the
permeability of the blood brain barrier. This study would be one of the first to examine the
concentrations of systemic cancer therapies in the cerebrospinal fluid (CSF) with matched
serum samples. Additionally, the concentration of these therapies in brain metastasis
surgical specimens would be of particular interest to correlate with serum and CSF levels,
length of time on therapy, and latency to developing brain metastases in future studies.

As participants in this study, patients scheduled for a lumbar puncture per their standard of
care treatment will be subject to a withdrawal of 15cc's of cerebrospinal fluid for
pharmacokinetic analysis. They will also have a blood draw of 5mL within 2 hours of the
lumbar puncture for serum pharmacokinetics. If the patient is eligible for and elects to
proceed with surgical resection of a brain metastasis, optional CSF and serum samples would
be drawn at the time of resection.

Inclusion Criteria:

1. Metastatic cancer patients on systemic anti-cancer therapy (chemotherapy, endocrine
therapy, HER2 targeted therapy, immune therapy).

2. Patients must be able to have a lumbar puncture within 2 half-lives of the last dose
of systemic therapy.

3. Patients undergoing an LP for any reason with known advanced cancer on systemic
anti-cancer therapy are eligible.

4. Patients with new or previously treated brain metastases are eligible.

5. Patients may have received prior stereotactic radiosurgery to the brain and/or whole
brain radiation.

6. No limitations on prior systemic or intrathecal therapies.

7. There are no restrictions on systemic therapy at enrollment.

8. Laboratory criteria: normal renal function: creatinine < 1.5 x upper limit of normal
(ULN)), liver function: bilirubin < 1.5 x ULN, transaminases < 2 x ULN, except in
known hepatic disease, wherein may be < 5 x ULN, and blood counts: WBC ≥ 2.0,
Neutrophils ≥1500, platelets ≥100,000, Hemoglobin ≥ 10.

9. Age > 18 years

10. Patients must have the ability to give informed consent.

11. Patients must have a signed informed consent form prior to enrollment on study.

Exclusion Criteria:

1. No history of lumbar surgery or other pre-existing spinal conditions that would
preclude a safe, reliable lumbar puncture.

2. Patients should have no significant psychiatric illness or medical illness that would
preclude the ability to comply with the protocol.