Natural Progesterone for the Treatment of Recurrent Glioblastoma

NCT05091866 | Terminated Early Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00002155NCI-2021-01498WINSHIP5184-20P30CA138292
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gliosarcoma; Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (3)

• Natural progesterone blood levels

  This analysis will be performed to determine what plasma drug levels can be achieved in recurrent glioblastoma (GBM) patients with subcutaneous administration of natural progesterone and whether this is in line with what was previously determined in healthy subjects.

  On day 1 (0, 30 minutes, 1, 2, 4, 6, 8 hours from drug injection) as well as at day 4 and day 8 prior to drug injections

• Incidence of adverse events

  The safety of this approach will be confirmed by assessing toxicity potentially attributable to the daily progesterone treatment. Toxicity will be determined by Common Terminology Criteria for Adverse Events version 5.0 criteria.

  Up to 2 years

• Overall response rate

  Will be looking for the fraction of patients that are able to maintain at least stable disease.

  Up to 2 years

Secondary Outcomes (2)

• Progression free survival (PFS)

  From the time of pre-treatment magnetic resonance imaging (MRI) to the time of either radiographic progression or death, whichever occurs first, assessed at 24 weeks

• Overall survival (OS)

  From the time of pre-treatment MRI to the time of death, assessed at 24 weeks

Other Outcomes (9)

• Progesterone receptor expression levels

  Up to 2 years

• Tumor mutational and genomic loss/gain factors

  Up to 2 years

• EORTC Quality-of-life (QOL) Questionnaire Core 30/Brain Cancer Module-20

  Up to 2 years

Study Arms (1)

Treatment (progesterone)

EXPERIMENTAL

Patients receive progesterone SC QD for up to 24 weeks in the absence of disease progression or unacceptable toxicity.

Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Biological: Therapeutic Progesterone

Interventions

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (progesterone)

Therapeutic Progesterone BIOLOGICAL

Given SC

Also known as: Corlutina, Corluvite, Corpus luteum hormone, Cyclogest, Gestiron, Gestone, Lipo-Lutin, Luteohormone, Lutocyclin, Lutocylin M, Lutogyl, Lutromone, Progestasert, Progesterone, Progestin, Progestogel, Progestol, Progeston, Prolidon, Proluton, Syngesterone, Utrogestan

Treatment (progesterone)

Questionnaire Administration OTHER

Ancillary studies

Treatment (progesterone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have pathologic confirmation of a glioblastoma or gliosarcoma diagnosis at initial surgery or second or later surgery
• Patients may have had up to two previous salvage agents administered for treatment of recurrent GBM (may be at 1st, 2nd or 3rd recurrence)
• Patients must be \>= 18 years of age
• Patients must be able to have magnetic resonance imaging (MRI) scans for disease follow up
• Recurrent GBM must consist of a minimum of 1 cm\^3 of contrast enhancing disease on high resolution T1 post-contrast sequence as defined on pre-treatment MRI obtained within 14 days of initiating therapy
• White blood cell (WBC) \>= 3,000/uL (=\< 14 days prior to registration)
• Absolute neutrophil count (ANC) \>= 1,500/uL (=\< 14 days prior to registration)
• Platelet count of \>= 75,000/uL (=\< 14 days prior to registration)
• Hemoglobin \>= 9.0 gm/dl (=\< 14 days prior to registration) (transfusion is allowed to reach minimum level)
• Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) =\< 2.0 x upper limit of normal (UNL) (=\< 14 days prior to registration)
• Bilirubin =\< 2 x UNL (=\< 14 days prior to registration)
• Creatinine =\< 1.5 mg/dL (=\< 14 days prior to registration)
• Patients must have a life expectancy of \>= 12 weeks
• Patients must have a Karnofsky Performance Status (KPS) \>= 60
• Patients who are women of childbearing potential must have a negative pregnancy test documented =\< 14 days prior to registration and agree to use adequate barrier contraceptive methods or abstinence for duration of study

You may not qualify if:

• Patients with pacemakers, aneurysm clips, neurostimulators, cochlear implants, metal in ocular structures, history of being a steel worker, or other incompatible implants which makes MRI safety an issue are excluded
• Patients that have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are excluded
• Patients with a history of severe hepatic dysfunction of disease are excluded
• Patients with a history of idiopathic jaundice, severe pruritus and pemphigoid gestationis during pregnancy are excluded
• Patients with a history of breast or genital tract cancer are excluded
• Patients with a history of any other invasive cancer (except non-melanoma skin cancer and excluding carcinoma in-situ), unless in complete remission and off all therapy for that disease for \>= 3 years, are ineligible
• Patients with an active infection or serious intercurrent medical illness are ineligible
• Patients who received any other in anti-tumor agents (including investigational ones) must be off therapy for 4 weeks prior to initiating progesterone on study
• Patient receiving anti-coagulation therapy are excluded
• Patient with active or recent (within 6 months) thromboembolic disease are excluded
• Patient with current ongoing therapy with estrogen/progesterone (including hormonal contraceptives) are excluded. Would need to stop this form of birth control at least 7 days prior to initiation of therapy to be eligible

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Gliosarcoma; Glioblastoma

Interventions

Progesterone; Progestins; Utrogestan

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Hui-Kuo G Shu, MD, PhD, FASTRO

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 14, 2021
• First Posted: October 25, 2021
• Study Start: April 11, 2022
• Primary Completion: December 20, 2024
• Study Completion: March 9, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)