S9005 Mifepristone in Meningioma

Double Blind Randomized Trial of the Anti-Progestational Agent Mifepristone In The Treatment of Unresectable Meningioma

To compare daily oral mifepristone vs placebo with respect to time to treatment failure in patients with unresectable meningioma.

Study Overview

• Status: Completed
• Conditions: Meningioma
• Intervention / Treatment: Drug: Mifepristone; Other: Placebo

Detailed Description

To compare daily oral mifepristone vs placebo with respect to time to treatment failure in patients with unresectable meningioma and to address issues of safety in this patient population.

• Study Type: Interventional
• Enrollment (Actual): 193
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 116 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have a histologically documented primary, recurrent or residual meningioma which is unresectable.

2. Patients must have active meningioma, which is defined to be one of the following:

   1. Progressive disease within the past 2 years.
   2. Recurrent Disease, as defined by the reappearance of a previously completely resected meningioma, within the past two years.
   3. New disease, defined as a diagnosis of meningioma within the previous two years
3. Patients must have measurable or evaluable disease which is documented on CT or MRI scan.
4. Patients should have already received radiotherapy unless radiotherapy is inappropriate due to tumor location(s) or unless radiotherapy, after discussion with the patient's physician, has been refused. If patients have received prior radiotherapy, this treatment must have been completed more than one year prior to study entry with documented progressive disease since completion of radiotherapy.
5. Patients must be 18 years or older, and must have a performance status 0-2 by Southwest Oncology Group criteria.
6. Patients must not have received prior cytotoxic chemotherapy for meningioma.
7. Patients must have serum creatinine, SGOT, and bilirubin ≤ 2 x IULN.
8. Patients requiring simultaneous administration of corticosteroids for cerebral edema must have been receiving a stable dose of corticosteroids for at least 4 weeks prior to study entry.
9. Patients receiving anti-epileptic medications are eligible. However barbiturates should be avoided if possible.
10. Patients with meningiomatosis (diffuse meningeal infiltration resulting in only nonevaluable meningeal thickening) are not eligible. However, patients with multiple measurable or evaluable meningioma tumor masses are eligible.
11. Patients with malignant meningioma are not eligible. Malignant meningioma is defined as meningioma that demonstrates hypercellularity, loss of architecture, nuclear pleomorphism, numerous mitoses, focal necrosis, and brain invasion.
12. Patients who have had additive or ablative modulation of sex hormone or glucocorticoid pathways within the preceding 3 months (not including stable corticosteroid therapy for cerebral edema) are not eligible. Such modulations include but are not limited to birth control pills, bilateral oophorectomy or orchiectomy, progestational inserts, oral or vaginal exogenous estrogens, androgens or antiandrogens, progestational agonists, tamoxifen, aminoglutethimide, o,p-DDD, ACTH, glucocorticoids not for cerebral edema, and leuprolides (or other LH-RH inhibitors). Patients must not have received prior mifepristone therapy for meningioma.
13. Patients must not have serious intercurrent medical illness; that is, any illness that in the opinion of the investigator would prevent following the study regimen.
14. Patients with clinical adrenal insufficiency requiring exogenous corticosteroid replacement are not eligible.
15. Patients with a known allergy to mifepristone are not eligible.
16. Patients with base of brain, cavernous sinus or optic nerve meningiomas or with visual symptoms must have a formal visual field examination.
17. Pregnant or lactating women may not participate. Pre-menopausal women and men of reproductive potential may not participate unless they have agreed to use an effective local contraceptive method (such as a condom, diaphragm, or IUD) or abstinence during and for 3 months after study therapy.

18. Patients with other prior or concurrent malignancy within the preceding 5 years, except surgically treated squamous or basal cell skin cancer or cervical cancer in situ, are not eligible.

    -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Mifepristone 200 mg orally daily for two years	Drug: Mifepristone; a 19 norsteroid with anti-progesterone and anti glucocorticoid activity which competitively inhibits binding of the hormone to its receptor; Other Names: RU-486
Placebo Comparator: Arm 2; Placebo orally daily for two years	Other: Placebo; placebo matching mifepristone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Treatment Failure	From date of registration to first date of documentation of one of the following: Progression (clear worsening of evaluable disease must be confirmed by 2 investigators).; Significant deterioration of at least one neurologic symptom; Discontinuation of treatment for any reason.; Death from any cause.	6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Patients will be followed for adverse events as defined by the SWOG toxicity criteria	two years after beginning treatment

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Director: Charles Blanke, MD, Oregon Health and Sciences University

Publications and helpful links

Helpful Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Study record dates

Study Major Dates

• Study Start: August 1, 1992
• Primary Completion (Actual): October 1, 2001
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: January 6, 2017
• First Submitted That Met QC Criteria: January 6, 2017
• First Posted (Estimate): January 10, 2017

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Unresectable
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Meningioma; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Abortifacient Agents; Luteolytic Agents; Abortifacient Agents, Steroidal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Menstruation-Inducing Agents; Mifepristone
• Other Study ID Numbers: SWOG-9005; U10CA032102 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://swog.org/Visitors/Download/Policies/Policy43.pdf