Oral Capecitabine and Temozolomide (CAPTEM) for Newly Diagnosed GBM

There were an estimated 22,000 new cases of brain cancers in 2015 in the United States, and
15,000 deaths (Howlader et al., 2014). Glioblastoma (WHO IV), and Anaplastic Astrocytoma (WHO
III), are the most common brain cancers, respectively, representing over 70% of all malignant
gliomas (ABTA, 2015).

Though rare, there is no cure, and the prognosis for these tumors is poor. Survival at 5
years for all CNS cancers is approximately 33.3 % (Howlader et al., 2014). For GBM, the most
lethal of the tumors, with the current standard of care median survival is 14.6 months
(Walid, 2008). Relative survival with GBM at five years is approximately only 5% (Ostrom et
al. CBTRUS 2014).

For newly diagnosed tumors, the current standard of care recommends a multi-modal approach
with surgery to remove the tumor, when possible, followed by 6 weeks of radiation and a
concurrent daily dose of temozolomide (Stupp et al. 2005). This is known as the Stupp
protocol (Stupp et al. 2005). Patients then have a one-month rest period with no treatment,
followed by "maintenance" temozolomide, given five days out of every 28 days, for a minimum
of six months. Some providers keep patients on temozolomide beyond 6 months, or until disease
progression.

Therefore, more therapies are needed to help improve survival, reduce time to recurrence and
improve quality of life for these patients. This trial proposes to improve the current
standard of care by enhancing the efficacy of an active drug temozolomide, currently used for
treatment of GBM.

Inclusion Criteria:

1. Be capable of giving informed consent.

2. Have a pathology proven diagnosis of any of newly diagnosed Glioblastoma Multiforme
WHO IV

3. Have completed the first part of standard of care chemo-radiation (Stupp), for 6
weeks, and not started the maintenance phase of temozolomide

4. Agree to use effective barrier contraception while on treatment and for 2 months
thereafter, if of childbearing potential

5. Have a life expectancy > 3 months

6. Be between the ages of 18 to 74

7. Have a performance status KPS 70 or greater

8. Be able to swallow pills and capsules

9. Be able to tolerate oral chemotherapeutic medications, with no health threatening
allergies or side effects, based on lab and clinical findings

10. Have adequate bone marrow function, liver function and renal function before
commencing therapy

Exclusion Criteria:

1. Prior chemotherapy with capecitabine or temozolomide for other prior malignancies.
Patients previously treated with continuous infusion 5-FU or any schedule of DTIC,
which are similar to capecitabine and temozolomide, respectively, will be excluded.

2. Prior chemotherapies for newly diagnosed GBM or AA, other than temozolomide during
radiation.

3. Patients with a history of severe hypersensitivity reaction to capecitabine, 5-FU,
temozolomide (i.e. anaphylaxis or anaphylactic reactions),

4. Serious medical or psychiatric illness preventing informed consent or treatment (e.g.,
serious infection)

5. Prior malignancies in the last 5 years other than curatively treated carcinoma in-situ
previously treated with curative intent (cancer free for the past one year).

6. Performance status, KPS < 70

7. Inability to swallow pills and capsules

8. Concurrent chemotherapy or treatment for the active disease, including devices such as
Optune, high dose vitamin supplements, or any other chemotherapy

9. Patients taking concomitant medications such as Coumadin and phenytoin medications,
need to be excluded because of interactions with capecitabine

10. Patients with previously documented CAD will need to be evaluated by cardiology prior
to start to help risk stratify for capecitabine tolerance

11. Patients with renal insufficiency or hepatic insufficiency

12. Patients with coagulopathies

13. Women who are pregnant or lactating.