PRIMARY OBJECTIVES:~I. To determine that the pharmacokinetics of natural progesterone given to recurrent glioblastoma [GBM] patients by subcutaneous injection is consistent with previous determinations made given subcutaneously using the aqueous formulation of progesterone.~II. To determine the safety of administering daily subcutaneous natural progesterone for the treatment of patients with recurrent GBMs.~III. To determine the rate of stable disease (SD) or better (partial response [PR] or complete response [CR]) at 8 weeks in eligible patients with recurrent GBM treated with daily subcutaneous natural progesterone.~SECONDARY OBJECTIVES:~I. To determine and compare the progression free survival of eligible patients with recurrent GBM compared with matched historical controls treated with a range of standard therapies.~II. To determine and compare the overall survival of eligible patients with recurrent GBM compared with matched historical controls treated with a range of standard therapies.~EXPLORATORY OBJECTIVES:~I. To determine whether progesterone receptor levels within the tumor correlates with response to daily subcutaneous natural progesterone.~II. To determine if other intrinsic tumor factors (mutations and genomic loss/gains) correlates with response to daily subcutaneous natural progesterone.~III. To determine if the absolute values or changes in the level of serum biomarkers correlates with response to daily subcutaneous natural progesterone.~IV. To determine the quality-of-life (QOL) by validated instruments of eligible patients with recurrent GBM treated with daily subcutaneous natural progesterone and assess whether this differs from historical controls.~OUTLINE:~Patients receive progesterone subcutaneously (SC) once daily (QD) for up to 24 weeks in the absence of disease progression or unacceptable toxicity.
This early phase I trial identifies the best dose, possible benefits and/or side effects of natural progesterone in treating patients with glioblastoma that has come back (recurrent). Progesterone is a type of hormone made by the body that plays a role in the menstrual cycle and pregnancy. Progesterone may help control tumor growth and spread in patients with glioblastoma.