Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Gliosarcoma

Disease Attributes

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Hormones

Progestins

Progesterone

Hormone Antagonists

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

Quality-of-Life Assessment

Questionnaire Administration

Therapeutic Progesterone

Agnes G. Harutyunyan

Hui-Kuo G. Shu, MD, PhD, FASTRO

Hui-Kuo G Shu, MD, PhD, FASTRO

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.

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.

Natural Progesterone for the Treatment of Recurrent Glioblastoma

Pilot Study of Subcutaneously Administered Natural Progesterone for the Treatment of Recurrent GBM

Original tumor and any recurrent tumor samples will be assessed for progesterone receptor expression levels by immunohistochemistry and these results will be correlated with response assessment to determine whether there is any correlation.

Each of the tumor mutational and genomic loss/gain factors will be scored and these results will be correlated with response assessment to determine whether there is any correlation.

Serial QOL assessments will be determined in patients and compared with historical cohorts to determine whether there is any difference in patients treated with subcutaneous progesterone for recurrent GBM.

YKL-40 will be quantitated at the specific time points (pre-treatment, 4 weeks, 8 weeks) with specific levels and changes in levels recorded. These results will be correlated with response assessment to determine whether there is any correlation.

Matrix Meteloproteinase-9 (MMP-9) will be quantitated at the specific time points (pre-treatment, 4 weeks, 8 weeks) with specific levels and changes in levels recorded. These results will be correlated with response assessment to determine whether there is any correlation.

Gilal Fibrillary Acidic Protein will be quantitated at the specific time points (pre-treatment, 4 weeks, 8 weeks) with specific levels and changes in levels recorded. These results will be correlated with response assessment to determine whether there is any correlation.

C-Reactive Protein will be quantitated at the specific time points (pre-treatment, 4 weeks, 8 weeks) with specific levels and changes in levels recorded. These results will be correlated with response assessment to determine whether there is any correlation.

Soluble CD14 will be quantitated at the specific time points (pre-treatment, 4 weeks, 8 weeks) with specific levels and changes in levels recorded. These results will be correlated with response assessment to determine whether there is any correlation.

Soluble CD23 will be quantitated at the specific time points (pre-treatment, 4 weeks, 8 weeks) with specific levels and changes in levels recorded. These results will be correlated with response assessment to determine whether there is any correlation.

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.

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.

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

Patients on this study will be followed for PFS. In addition to the 24 weeks PFS, actuarial PFS curves will be assessed and compared to historical controls.

Patients on this study will be followed for OS. In addition to the 24 weeks OS, actuarial OS curves will be assessed and compared to historical controls.

National Cancer Institute (NCI)

Emory University

Principal Investigator

Skin and Connective Tissue Diseases

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Breast Neoplasms

Osteoporosis

Hot Flashes

Breast Diseases

Skin Diseases

Bone Diseases

Bone Diseases, Metabolic

Metabolic Diseases

Menopause

Estrogens, Conjugated (USP)

Estrogens

therapeutic progesterone

conjugated estrogens

Jenni Parmar, RN

RATIONALE: Hormone replacement therapy may be effective in relieving symptoms of menopause, such as hot flashes, night sweats, and vaginal dryness, without causing a recurrence of breast cancer.

PURPOSE: This randomized clinical trial is studying hormone replacement therapy to see how well it works in relieving symptoms of menopause in postmenopausal women with previous stage I or stage II breast cancer.

OBJECTIVES:

* Compare disease-free survival and overall survival of postmenopausal women with prior stage I or II breast cancer treated with hormone replacement therapy (HRT) vs nonhormonal alternatives to HRT.
* Compare relief of menopausal symptoms and quality of life of patients treated with these regimens.
* Compare cardiovascular and osteoporotic events in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, age (\< 40 years vs ≥ 40 years), and years from diagnosis (≤ 2 vs \> 2 to \< 5 vs ≥ 5). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral or transdermal HRT comprising estrogen with or without progesterone for at least 2 years.
* Arm II: Patients are offered advice on nonhormonal HRT alternatives. Menopausal symptoms are assessed at baseline, at 3, 6, and 12 months, every 6 months for 4 years, and then annually thereafter. Quality of life is assessed at baseline, at 3, 6, and 12 months, every 6 months for 1 year, and then annually thereafter.

Patients are followed every 6 months for 3 years and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 2,800-3,000 patients (1,400-1,500 per treatment arm) will be accrued for this study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Natural Progesterone for the Treatment of Recurrent Glioblastoma	NCT05091866	Gliosarcoma Recurrent Gliob...	Quality-of-Life... Questionnaire A... Therapeutic Pro...	18 Years -	Emory University
Hormone Replacement Therapy in Relieving Menopausal Symptoms in Postmenopausal Women With Previous Stage I or Stage II Breast Cancer	NCT00079248	Breast Cancer Hot Flashes Menopausal Symp... Osteoporosis	therapeutic pro... conjugated estr...	-	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for therapeutic progesterone