RECRUITING

Minnelide and Osimertinib for the Treatment of Advanced EGFR Mutated Non-Small Cell Lung Cancer

Talk to us

Conditions

Advanced Lung Non-Small Cell CarcinomaLocally Advanced Lung Non-Small Cell CarcinomaStage III Lung Cancer AJCC v8Stage IIIA Lung Cancer AJCC v8Stage IIIB Lung Cancer AJCC v8Stage IIIC Lung Cancer AJCC v8Stage IV Lung Cancer AJCC v8Stage IVA Lung Cancer AJCC v8Stage IVB Lung Cancer AJCC v8Unresectable Lung Non-Small Cell Carcinoma

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase Ib trial tests the side effects and best dose of minnelide when given together with osimertinib for the treatment of non-small cell lung cancer that has spread to other places in the body (advanced) and has a change (mutation) in a gene called EGFR. Minnelide is a biologically inactive compound that can be broken down in the body to produce a drug that rapidly releases the active compound triptolide when exposed to phosphatases in the bloodstream. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Minnelide and osimertinib may work better in treating patients with EGFR mutant advanced non-small cell lung cancer.

Official Title

A Phase 1b Open-Label, Dose-Escalation, Safety, and Pharmacodynamic Study of Minnelide™ Capsules Given in Combination With Osimertinib in Patients With EGFR Mutated NSCLC

Quick Facts

Study Start:2022-03-07
Study Completion:2026-10-28
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05166616

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Documented informed consent of the participant and/or legally authorized representative
  2. * Assent, when appropriate, will be obtained per institutional guidelines
  3. * Agreement to two research biopsies
  4. * If tumor is unbiopsiable or not safely biopsied, exceptions may be granted with study principal investigator (PI) approval
  5. * Age: \>= 18 years
  6. * Karnofsky performance \>= 70%
  7. * Histologically confirmed advanced non-small cell lung cancer (NSCLC). Patients with locally advanced NSCLC must not be candidates for surgical resection, radiation, or chemoradiation with curative intent
  8. * The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations known to be associated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination with other epidermal growth factor receptor (EGFR) mutations, which may include T790M
  9. * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  10. * Tumor progression after receiving standard/approved osimertinib
  11. * Fully recovered from the acute toxic effects (except alopecia) to =\< grade 1 to prior anti-cancer therapy. Grade 2 neuropathy is allowed
  12. * Absolute neutrophil count (ANC) \>= 1,500/mm\^3 (within 14 days prior to day 1 of protocol therapy)
  13. * NOTE: Growth factor is not permitted within 14 days of ANC assessment
  14. * Platelets \>= 100,000/mm\^3 (within 14 days prior to day 1 of protocol therapy)
  15. * NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
  16. * Hemoglobin \>= 9 g/dL (within 14 days prior to day 1 of protocol therapy)
  17. * Total bilirubin =\< 1.5 X ULN (unless has Gilbert's disease). Total bilirubin \< 3 x ULN in the presence of documented Gilbert's disease (within 14 days prior to day 1 of protocol therapy)
  18. * Aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN) (if liver metastases are present, then =\< 5 x ULN is allowed) (within 14 days prior to day 1 of protocol therapy)
  19. * Alanine aminotransferase (ALT) =\< 2.5 x ULN if liver metastases are present, then =\< 5 x ULN is allowed) (within 14 days prior to day 1 of protocol therapy)
  20. * Alkaline phosphatase =\< 2.5 x ULN if liver metastases are present, then =\< 5 x ULN is allowed) (within 14 days prior to day 1 of protocol therapy)
  21. * Serum creatinine within normal limits, OR creatinine clearance of \>= 60 mL/min per 24 hour urine test for patients with creatinine levels above ULN (within 14 days prior to day 1 of protocol therapy)
  22. * Creatinine clearance (CrCl, by Cockcroft-Gault) is utilized for all patients to allow for evaluation of the effect of CrCl on the minnelide/triptolide exposures
  23. * If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) =\< 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)
  24. * If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
  25. * If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)
  26. * If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
  27. * Albumin \>= 3.0 /dL (within 14 days prior to day 1 of protocol therapy)
  28. * Urinalysis - no clinically significant abnormalities (within 14 days prior to day 1 of protocol therapy)
  29. * QT corrected (QTc) =\< 470 ms (using the Bazett's formula)
  30. * Note: To be performed within 28 days prior to Day 1 of protocol therapy.
  31. * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 14 days prior to day 1 of protocol therapy)
  32. * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  33. * Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 weeks after the last dose of protocol therapy. Contraception must be continued following discontinuation of the study drugs for at least five half-lives of both study drugs
  34. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
  35. * Female patients of childbearing potential must:
  36. * Agree to practice 1 highly effective method of non-hormonal contraception and one additional effective (barrier) method at the same time, from the time of signing the informed consent through 180 days after the last dose of study drug, or
  37. * Agree to practice true abstinence, when is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g. calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
  38. * Agree not to donate eggs (ova) during the course of this study or 180 days after receiving their last dose of study drug. Agree not to breast-feed for the duration of treatment through 6 months post treatment.
  39. * Male patients of childbearing potential must:
  40. * Agree to practice effective barrier contraception during the entire study treatment period and through 180 days after the last dose of study drug, or
  41. * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g. calendar, ovulation, symptothermal, postovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception. Female and male condoms should not be used together.)
  42. * Agree not to donate sperm during the course of this study or within 180 days after receiving their last dose of study drug.
  43. * Patients must be able to swallow and retain oral medications
  44. * Previously tolerant of osimertinib at 80 mg QD
  1. * Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 21 days prior to day 1 of protocol therapy (6 weeks for nitrosoureas or Mitomycin C). Exceptions to this exclusion are brain radiation and osimertinib
  2. * Biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
  3. * Strong CYP3A4 inducers/ inhibitors within 14 days prior to day 1 of protocol therapy
  4. * Patients receiving class 1A or class III antiarrhythmic agents within 14 days prior to Day 1 of protocol therapy
  5. * Herbal and alternative (eg. turmeric, cannabidiol, ginseng) medications within 7 days prior to Day 1 of protocol therapy
  6. * Clarithromycin, loperamide, ondansetron within 7 days prior to day 1 of protocol therapy
  7. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  8. * Active diarrhea
  9. * Clinically significant uncontrolled illness
  10. * Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
  11. * Prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated 5 or more years prior to study entry with no subsequent evidence of recurrence. Patients with a history of low grade (Gleason score =\< 6 = Gleason Group 1) localized prostate cancer will be eligible even if diagnosed less than 5 years prior to study entry
  12. * Females only: Pregnant or breastfeeding
  13. * Any malabsorption condition
  14. * Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
  15. * New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
  16. * Clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroid medication for 1 week prior to the first dose of study drug and have completed radiation 2 weeks prior to the first dose of study drug
  17. * Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  18. * Diagnosis of congenital long QT syndrome
  19. * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Contacts and Locations

Principal Investigator

Erminia Massarelli
PRINCIPAL_INVESTIGATOR
City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center
Duarte, California, 91010
United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

  • Erminia Massarelli, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-03-07
Study Completion Date2026-10-28

Study Record Updates

Study Start Date2022-03-07
Study Completion Date2026-10-28

Terms related to this study

Additional Relevant MeSH Terms

  • Advanced Lung Non-Small Cell Carcinoma
  • Locally Advanced Lung Non-Small Cell Carcinoma
  • Stage III Lung Cancer AJCC v8
  • Stage IIIA Lung Cancer AJCC v8
  • Stage IIIB Lung Cancer AJCC v8
  • Stage IIIC Lung Cancer AJCC v8
  • Stage IV Lung Cancer AJCC v8
  • Stage IVA Lung Cancer AJCC v8
  • Stage IVB Lung Cancer AJCC v8
  • Unresectable Lung Non-Small Cell Carcinoma