RECRUITING

WSD0922-FU for the Treatment of Glioblastoma, Anaplastic Astrocytoma, or Non-small Cell Lung Cancer with Central Nervous System Metastases

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Conditions

Anaplastic Astrocytoma, IDH-WildtypeGlioblastoma, IDH-WildtypeMetastatic Lung Non-Small Cell CarcinomaMetastatic Malignant Neoplasm in the Central Nervous System

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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 I trial studies the side effects and best dose of WSD0922-FU for the treatment of glioblastoma, anaplastic astrocytoma, or non-small cell lung cancer that has spread to the central nervous system (central nervous system metastases). WSD0922-FU is a targeted treatment which blocks the EGFR protein - a strategy that has led to a lot of benefit in patients with many different cancers. WSD0922-FU may also be able to get into cancers in the brain and spinal cord and help patients with brain and spinal cord cancers.

Official Title

Phase I Study to Evaluate Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of WSD0922-FU

Quick Facts

Study Start:2019-12-20
Study Completion:2025-12-20
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04197934

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. * Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort
  2. * Histolopathological and/or molecular confirmation of either glioblastoma, IDH wildtype (GBM), (as defined by either the 2016 or 2021 World Health Organization \[WHO\] classifications) anaplastic astrocytoma, IDH wildtype (AA) (as defined by the 2016 WHO classification) or non-small cell lung cancer (NSCLC)
  3. * EGFR Status:
  4. * GBM/AA must either EGFR amplification and/or any activating EGFR mutation (e.g. A289T, EGFRvIII , etc.)
  5. * NSCLC must have a confirmed activating EGFR mutation (e.g. Del19, L858R, EGFRvIII, G719A, L861Q, T790M, C797S, etc.)
  6. * Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts
  7. * Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort:
  8. * Diagnosis: Histological or molecular confirmation of either glioblastoma, IDH wildtype (GBM) (as defined by either the 2016 or 2021 WHO classifications) or anaplastic astrocytoma, IDH wildtype (AA) (as defined by the 2016 WHO classification)
  9. * EGFR status: GBM/AA must have EGFRvIII mutation
  10. * Brain Tumor Penetration (BTP) Cohort:
  11. * Diagnosis: Histopathological or molecular confirmation of either glioblastoma, IDH wildtype (GBM) (as defined by either the 2016 or 2021 WHO classifications) or anaplastic astrocytoma, IDH wildtype (AA) (as defined by the 2016 WHO classification)
  12. * EGFR status: GBM/AA must have been previously demonstrated to have either EGFR amplification and/or any activating EGFR mutation based on any prior resection
  13. * Non-Small Cell Lung Cancer (NSCLC) cohort:
  14. * Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC)
  15. * EGFR status: NSCLC must have confirmed activating EGFR mutation. Following protocol amendment 7, NSCLC must have EGFR C797S mutation.
  16. * Registration -Inclusion Criteria Specific to Dose Escalation Cohort
  17. * Previous treatments:
  18. * Patients with GBM/AA must have been previously treated with radiation and temozolomide
  19. * Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. gefitinib, erlotinib, afatinib, or osimertinib)
  20. * Radiographic progression:
  21. * Patients with GBM/AA must have radiographic progression based on RANO criteria
  22. * Patients with NSCLC must have new or radiographic progression in the central nervous system (brain metastases and/or leptomeningeal metastases). Positive confirmation of CSF cytology is both necessary and sufficient to define the presence of leptomeningeal metastases for patients in this study. Patients with positive CSF cytology and brain metastases will be categorized as "leptomeningeal metastases."
  23. * Measurable disease
  24. * Eastern Cooperative Oncology Group (ECOG) 0 or 1. For patients with NSCLC with leptomeningeal metastases, ECOG 2 is also acceptable
  25. * Registration - Inclusion Criteria Specific to Dose Expansion Cohorts
  26. * Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort:
  27. * Previous treatments: Patients must have been previously treated with radiation and temozolomide. First recurrence only (no additional systemic therapies have been administered for recurrent disease)
  28. * Radiographic progression: Patients with GBM/AA must have radiographic progression based on RANO criteria
  29. * Patients remain eligible for enrollment if the recurrent disease has been surgically removed
  30. * Performance status: ECOG 0 or 1
  31. * Brain Tumor Penetration (BTP) Cohort:
  32. * Previous treatments: Patients must have been previously treated with radiation and temozolomide
  33. * Radiographic progression: Patients with GBM/AA must have radiographic progression based on RANO criteria
  34. * Therapeutic surgical resection of GBM/AA required as part of routine clinical care
  35. * Performance status: ECOG 0 or 1
  36. * Non-Small Cell Lung Cancer (NSCLC) cohort:
  37. * Previous treatments: No limitations
  38. * Radiographic progression: Patients must have radiographic progression based on RECIST 1.1 criteria.
  39. * Measurable Disease
  40. * Performance Status: ECOG 0 or 1
  41. * Registration - Inclusion Criteria Common to Dose Escalation and Dose Expansion Cohorts:
  42. * Age \>= 18 years old
  43. * Ability to understand and the willingness to sign a written informed consent document
  44. * Hemoglobin \>= 9.0 g/dL (obtained =\< 14 days prior to registration)
  45. * Leukocytes \>= 3.0 x 10\^9/L (obtained =\< 14 days prior to registration)
  46. * Absolute neutrophil count \>= 1.5 x 10\^9/L (obtained =\< 14 days prior to registration)
  47. * Platelets \>= 100 x 10\^9/L (obtained =\< 14 days prior to registration)
  48. * International normalized ratio (INR) =\< 1.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration)
  49. * Patients on a stable dose of anti-coagulation therapy will be allowed to participate if they have no signs of bleeding or clotting and the INR/prothrombin time (PT) and partial thromboplastin time (PTT)/activated (a)PTT results are compatible with an acceptable risk-benefit ratio as per the investigator's discretion
  50. * aPTT =\< 1.5 x ULN (obtained =\< 14 days prior to registration)
  51. * Patients on a stable dose of anti-coagulation therapy will be allowed to participate if they have no signs of bleeding or clotting and the INR/PT and PTT/aPTT results are compatible with an acceptable risk-benefit ratio as per the investigator's discretion
  52. * Total bilirubin =\< 1.5 x ULN and =\< 3 mg/dL for patients with Gilbert's disease (obtained =\< 14 days prior to registration)
  53. * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN or =\< 5 x ULN if due to liver involvement by tumor (obtained =\< 14 days prior to registration)
  54. * Creatinine =\< 1.5 x ULN or estimated glomerular filtration rate (estimated glomerular filtration rate \[eGFR\]) \>= 60 mL/minute (obtained =\< 14 days prior to registration)
  55. * Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only
  56. * Provision of signed and dated written informed consent prior to any study specific procedures, sampling, and analyses
  57. * Willingness to provide mandatory blood specimens for correlative research
  58. * Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study i.e., active treatment and clinical follow-up)
  59. * Male and female patients of child bearing potential must be willing to use contraception, (i.e., condoms, birth control) while on study and until 3 months after the last dose of study drug is taken
  60. * Must be willing to take light-protective measures during the study and for 2 weeks after their last dose of WSD0922-FU
  61. * Must have a minimum life expectancy of \>= 3 months
  62. * Must be stable on no more than 2 mg of dexamethasone (or equivalent steroids) per day. Steroid dose adjustments should be minimized during cycle 1 of therapy. Patients enrolling to the BTP expansion cohort do not have any restrictions on current steroid/dexamethasone dosing.
  63. * Must not take enzyme-inducing anticonvulsants treatment for at least 2 weeks prior to enrollment. Patients on enzyme-inducing anticonvulsants will be changed to non-enzyme inducing anticonvulsants
  64. * Strong inducers and strong inhibitors of CYP3A should be discontinued at least 14 days prior to registration
  65. * Willingness to provide mandatory tissue specimens for correlative research (BTP cohort only)
  1. * Registration - Exclusion Criteria for Dose Escalation and Dose Expansion
  2. * Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  3. * Pregnant persons
  4. * Nursing persons
  5. * Persons of childbearing potential who are unwilling to employ adequate contraception
  6. * Any of the following prior therapies:
  7. * Any cytotoxic chemotherapy or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen =\< 14 days prior to registration
  8. * In patients with NSCLC, treatment with an EGFR TKI (e.g., erlotinib, gefitinib, afatinib or osimertinib) must be discontinued prior to registration. Additionally, prior EGFR TKI therapy must be discontinued within 8 days or 5 half-lives, whichever is longer, prior to study therapy initiation. If sufficient wash-out time has not occurred due to schedule or PK properties, an alternative appropriate wash-out time based on known duration and time to reversibility of drug related adverse events could be agreed upon by the Investigator and Wayshine)
  9. * Radiation therapy to the brain =\< 12 weeks prior to registration
  10. * Patients with GBM/AA must not have received (i) nitrosoureas within 42 days of registration, (ii) any chemotherapy or experimental therapy within 28 days or 5 half-lives, whichever is longer, prior to registration
  11. * Patients with GBM/AA must not have received prior anti-EGFR or EGFRvIII therapies (erlotinib, gefitinib, afatinib, osimertinib, ABT-414, ABBV-221, AMG-595, AMG-596 etc.)
  12. * Patients with GBM/AA who have been treated with bevacizumab within the last four months are not eligible
  13. * Received prior systemic biologic therapy (CAR-T, anti-PD-1 / anti-PD-L1, anti-CTLA-4, etc.) within 28 days prior to registration.
  14. * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required
  15. * Subjects who are human immunodeficiency virus (HIV), hepatitis virus B (HBV), and/or hepatitis virus C (HCV) positive
  16. * Uncontrolled inter-current illness including, but not limited to:
  17. * Symptomatic CNS complications that require urgent neurosurgical or medical (e.g. mannitol) intervention
  18. * Seizures requiring a change in anti-epileptic medications (addition of new anti-epileptic or increase in dose) =\< 2 weeks of registration
  19. * Known intracranial hemorrhage which is unrelated to tumor
  20. * Significant medical or psychiatric illness that would interfere with compliance and ability to tolerate treatment as outlined in the protocol
  21. * Illness/social situations that would limit compliance with study requirements
  22. * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  23. * Patients with a "currently active" second malignancy other than non-melanoma skin cancers and carcinoma-in-situ of the cervix. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for more than three years prior to registration
  24. * Any of the following cardiac criteria:
  25. * A marked baseline prolongation of QT/corrected QT (QTc) interval
  26. * (e.g., repeated demonstration of a QTc interval \> 480 milliseconds (ms) (Common Terminology Criteria for Adverse Events \[CTCAE\] grade 1) using Fridericia's QT correction formula
  27. * A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome)
  28. * The use of concomitant medications that prolong the QT/QTc interval
  29. * Patients confirmed to have a cis double mutation (Del19/T790M or L858R/T790M) or cis triple mutation (Del19/T790m/C797S or L858R/T790M/C797S)
  30. * Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. History of hypersensitivity to active or inactive excipients of WSD0922-FU or drugs with a similar chemical structure or class to WSD0922-FU
  31. * Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0922-FU
  32. * Inadequate bone marrow reserve or organ function
  33. * Patients with NSCLC LM who are unable to undergo collection of CSF
  34. * Patients who are unable to tolerate dairy (GBM/AA cohort only). This is to ensure that patients on this cohort can participate in the food effect study

Contacts and Locations

Study Contact

Clinical Trials Referral Office
CONTACT
855-776-0015
mayocliniccancerstudies@mayo.edu

Principal Investigator

Sani H. Kizilbash, M.D., M.P.H.
PRINCIPAL_INVESTIGATOR
Mayo Clinic in Rochester

Study Locations (Sites)

Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
United States

Collaborators and Investigators

Sponsor: Mayo Clinic

  • Sani H. Kizilbash, M.D., M.P.H., PRINCIPAL_INVESTIGATOR, Mayo Clinic in Rochester

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 Date2019-12-20
Study Completion Date2025-12-20

Study Record Updates

Study Start Date2019-12-20
Study Completion Date2025-12-20

Terms related to this study

Additional Relevant MeSH Terms

  • Anaplastic Astrocytoma, IDH-Wildtype
  • Glioblastoma, IDH-Wildtype
  • Metastatic Lung Non-Small Cell Carcinoma
  • Metastatic Malignant Neoplasm in the Central Nervous System