Study of Oral Mifepristone as Salvage Therapy in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

NCT02642939 | Terminated Phase 2

• 1 other identifier: MIF-01-2014
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, multicenter, single-stage phase II study of mifepristone in patients with advanced or metastatic NSCLC who have failed two or more previous chemotherapy regimens. The Investigator plans to enroll 18 evaluable patients in Stage 1, and additionally up to 22 evaluable patients in Stage 2 for a total of 40 evaluable patients. Participants will be followed for overall survival. Current salvage therapy in advanced NSCLC achieves a median progression free survival time of 10 weeks and overall survival of 10 months. The Investigator would like to provide evidence that mifepristone will increase the median progression-free survival time to 15 weeks and overall survival time of 16 months.

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (3)

• Overall Survival

  defined as the time from first dose of study drug to the date of death

  through study completion, an average of 16 months

• A. Improvement in Quality of Life (QoL)

  Participants complete QoL questionnaire EROTC QLQ-C30 every 8 weeks

  every 8 weeks from date of enrollment until end of study or the date of death from any cause, assessed using QoL questionnaire,assessed up to 56 months.

• B. Improvement in Quality of Life (QoL)

  Participants complete QoL questionnaire EROTC QLQ-LC13 (specific to lung cancer)

  every 8 weeks from date of enrollment until end of study or the date of death from any cause, assessed using QoL questionnaire,assessed up to 56 months.

Secondary Outcomes (3)

• Progression free survival

  median of 15 weeks from study enrollment until end of study or the date of first documented progression, assessed every 12 weeks by radiologic examination,assessed up to 56 months.

• Overall response rate

  assessed every 4 weeks, from date of enrollment until end of study or the date of death from any cause, assessed up to 56 months.

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  assessed every week for 1 month and then every 4 weeks, from date of enrollment until end of study or the date of death from any cause, assessed up to 56 months.

Study Arms (1)

mifepristone

EXPERIMENTAL

mifepristone 300 mg capsule per day, orally in 28-day cycles

Drug: Mifepristone

Interventions

Mifepristone DRUG

Mifepristone is an antagonist of the GR-II (glucocorticoid) receptor, yet has little affinity for the GR-I (mineralocorticoid) receptor. Mifepristone is also a potent antagonist at the progesterone receptor, and may block the androgen receptor to a limited degree.

Also known as: KORLYM®, C1073, CORLUXIN™ and CORLUX™.

mifepristone

Eligibility Criteria

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

You may qualify if:

• Each patient must meet the following criteria to be enrolled in the study
• Must understand and voluntarily sign an informed consent
• Age ≥ 18 years at the time of signing the informed consent
• Histological or cytological documented diagnosis of locally advanced, recurrent or metastatic (Stage IIIB or Stage IV) NSCLC
• Patients must have evidence of disease, measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
• Patients shall provide results of tumor testing for epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement, and if positive for EGFR mutation or ALK rearrangement shall have received appropriate targeted therapy prior to enrollment. If not previously tested, EGFR and ALK testing must be performed prior to study entry.
• Patients shall have progressed after two or more previous chemotherapy regimens for metastatic or locally advanced disease
• Patients must have recovered from any toxic effects and at least 3-4 weeks must have elapsed from the last dose of previous therapy, prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 3
• Life expectancy of at least 12 weeks
• Patients must have adequate bone marrow and renal/hepatic function at the screening visit, defined as:
• Absolute neutrophil count ≥ 1,500/mm3 without granulocyte colony-stimulating factor (G-CSF) support within 7 days preceding the lab assessment
• Platelet count ≥ 100,000/mm3, without transfusion within 7 days preceding the lab assessment
• Hemoglobin ≥ 9 g/dL, without transfusion support within 7 days preceding the lab assessment
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN)

You may not qualify if:

• Patients who meet any of the following criteria will not be permitted entry to the study:
• Pregnant or breast-feeding
• Women with a history of unexplained vaginal bleeding.
• Women with uterine hyperplasia - in pre-menopausal women hyperplasia \>18mm and in post-menopausal women hyperplasia of \>10mm Prior therapy with mifepristone
• Prior therapy with mifepristone
• Patients who have had recent systemic cytotoxic therapies or radiotherapy within 14 days prior to day 1 of cycle 1
• Use of cytotoxic chemotherapeutic agents, erythropoiesis-stimulating agents (ESA), or experimental agents (agents that are not commercially available) within 30 days of the first day of study drug treatment.
• Patients who have had any major surgery within 4 weeks prior to day 1 of cycle 1, or minor surgery within 2 weeks prior to day 1 of cycle 1
• For two weeks prior to first day of study drug treatment, administration of any of the following cytochrome P450 3A (CYP3A) inducers: phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, St. John's Wort; or CYP3A inhibitors: ketoconazole, itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir amprenavir, fosamprenavir, boceprevir, clarithromycin, conivaptan, lopinavir, posaconazole, saquinavir, telaprevir, telithromycin, or voriconazole
• Patients who are taking simvastatin or lovastatin. Patients should be switched to alternative therapies a minimum of 2 weeks before starting study drug
• Patients who have been treated with an investigational agent within 21 days prior to day 1 of cycle 1.
• Concomitant use of biological agents including growth factors
• Patients who require treatment with systemic corticosteroids for serious medical conditions or illnesses (e.g. immunosuppression after organ transplantation)
• Chronic liver disease as indicated by Child-Pugh score A (6) or greater
• History of significant cardiac disease. Significant cardiac diseases includes second/third degree heart block; significant ischemic heart disease; mean QTc interval \> 480 msec on at least two separate electrocardiograms (ECGs) prior to study start; poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea)

Sponsors & Collaborators

• Check, Jerome H., M.D., Ph.D.: lead
• Corcept Therapeutics: collaborator

Study Sites (1)

Cooper Institute for Reproductive Hormonal Disorders

Melrose Park, Pennsylvania, 19027, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Mifepristone; Corlux

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jerome H Check, MD,PhD

  Cooper Institute for Reproductive Hormonal Disorders

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2015
• First Posted: December 30, 2015
• Study Start: December 1, 2015
• Primary Completion: October 15, 2020
• Study Completion: October 15, 2020
• Last Updated: October 19, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: 1 year after completion of study

Locations

US (1)