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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04197934
Recruitment Status : Recruiting
First Posted : December 13, 2019
Last Update Posted : November 13, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Anaplastic Astrocytoma, IDH-Wildtype Glioblastoma, IDH-Wildtype Lung Non-Small Cell Carcinoma Metastatic Malignant Neoplasm in the Central Nervous System Metastatic Malignant Neoplasm in the Leptomeninges Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU Procedure: Therapeutic Conventional Surgery Phase 1

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Study Type : Interventional
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study to Evaluate Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of WSD0922-FUFU
Actual Study Start Date : December 20, 2019
Estimated Primary Completion Date : December 20, 2022
Estimated Study Completion Date : December 20, 2022


Arm Intervention/treatment
Experimental: Dose escalation (WSD0922-FU)
Patients receive WSD0922-FU PO QD or BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU
Given PO
Other Names:
  • BBB Penetrable EGFR/EGFRvIII Inhibitor WSD0922-FU
  • EGFR Mutant Inhibitor WSD0922-FU
  • WSD 0922-FU
  • WSD-0922-FU
  • WSD0922-FU

Experimental: Dose expansion Cohort I (WSD0922-FU)
Patients with GBM/AA receive WSD0922-FU PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU
Given PO
Other Names:
  • BBB Penetrable EGFR/EGFRvIII Inhibitor WSD0922-FU
  • EGFR Mutant Inhibitor WSD0922-FU
  • WSD 0922-FU
  • WSD-0922-FU
  • WSD0922-FU

Experimental: Dose expansion Cohort II (WSD0922-FU, surgery)
Patients with BTP receive a single dose of WSD0922-FU prior to surgery. Patients then undergo surgical resection of brain tumor. After surgery, patients receive WSD0922-FU PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU
Given PO
Other Names:
  • BBB Penetrable EGFR/EGFRvIII Inhibitor WSD0922-FU
  • EGFR Mutant Inhibitor WSD0922-FU
  • WSD 0922-FU
  • WSD-0922-FU
  • WSD0922-FU

Procedure: Therapeutic Conventional Surgery
Undergo surgical resection

Experimental: Dose expansion Cohort III (WSD0922-FU)
Patients with NSCLC LM receive WSD0922-FU PO on days 1 and 4 of cycle 0. Patients then receive WSD0922-FU PO BID on days 1-28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU
Given PO
Other Names:
  • BBB Penetrable EGFR/EGFRvIII Inhibitor WSD0922-FU
  • EGFR Mutant Inhibitor WSD0922-FU
  • WSD 0922-FU
  • WSD-0922-FU
  • WSD0922-FU




Primary Outcome Measures :
  1. Recommended phase 2 dose [ Time Frame: Up to 28 days ]
    The RP2D is either the maximum tolerated dose (MTD) or the highest dose tested (in the case that none of the doses are deemed higher than the MTD), whichever is higher.


Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 4-6 weeks after study completion ]
  2. Overall response rate [ Time Frame: Up to 5 years ]
    The overall response rate will be defined as the number of patients with a partial response (PR) or better that is confirmed in consecutive evaluations (at least 8 weeks apart) divided by the total number of evaluable patients. A 95% confidence interval will also be constructed using the properties of the binomial distribution.

  3. Duration of response (DOR) [ Time Frame: From the first occurrence of a PR (or better) and progression, assessed up to 5 years ]
    Duration of response is defined as the number of days between a patient's first occurrence of a PR (or better) and progression. If a patient goes off study prior to progression (for another reason) then they will be censored at that time. A time to event analysis will be performed utilizing the Kaplan-Meier method which will yield a median DOR.

  4. Progression Free Survival (PFS) [ Time Frame: From study entry to disease progression, assessed up to 5 years ]
    A patient's progression free survival time is the number of days between study entry and disease progression. These data will be analyzed utilizing the Kaplan-Meier method which will yield a median PFS time.


Other Outcome Measures:
  1. Maximum plasma Concentration [Cmax] of WSD0922-FU after a single dose of WSD0922-FU [ Time Frame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours ]
  2. Area under the plasma concentration versus time curve (AUC) of WSD022-FU after a single dose of WSD0922-FU [ Time Frame: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours of day 1 of cycles 1 and 2; and pre-dose day 1 of cycles 3 and 4 ]
  3. Maximum plasma Concentration [Cmax] of WSD0922-FU after multiple doses of WSD0922-FU [ Time Frame: Cycle 1 Day 15: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours ]
  4. Area under the plasma concentration versus time curve (AUC) of WSD022-FU after multiple doses of WSD0922-FU [ Time Frame: Cycle 1 Day 15: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours ]
  5. CSF concentration of WSD0922-FU after multiple doses of WSD0922-FU (Dose Expansion - NSCLC leptomeningeal metastases (NSCLC LM) cohort only). [ Time Frame: Cycle 2 Day 1 ]
  6. Brain tumor concentration of WSD0922-FU after a single dose of WSD0922-FU (Dose Expansion - Brain tumor penetration (BTP) cohort only). [ Time Frame: Cycle 0 Day 1 ]
  7. Tumor EGFR inhibition after a single dose of WSD0922-FU (Dose Expansion - Brain tumor penetration (BTP) cohort only). [ Time Frame: Cycle 0 Day 1 ]
  8. Effect of food on Maximum plasma Concentration [Cmax] of WSD0922-FU after a single dose of WSD0922-FU (Dose Expansion - NSCLC LM cohort only). [ Time Frame: Cycle 0 Day 1 and Cycle 0 Day 4 ]
  9. Effect of food on Area under the plasma concentration versus time curve (AUC) of WSD022-FU after a single dose of WSD0922-FU (Dose Expansion - NSCLC LM cohort only). [ Time Frame: Cycle 0 Day 1 and Cycle 0 Day 4 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort
  • Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC)
  • EGFR Status:

    • GBM/AA must have EGFR amplification and/or EGFRvIII mutation
    • NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q)
  • Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts
  • Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort:

    • Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA)
    • EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation
  • Brain Tumor Penetration (BTP) Cohort:

    • Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA)
    • EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection
  • Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort:

    • Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC)
    • EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q)
  • Registration -Inclusion Criteria Specific to Dose Escalation Cohort
  • Previous treatments:

    • Patients with GBM/AA must have been previously treated with radiation and temozolomide
    • 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) and at least one line of chemotherapy (doublet chemotherapy such as carboplatin/paclitaxel, carboplatin/gemcitabine, cisplatin/paclitaxel, cisplatin/gemcitabine; single agent such as pemetrexed, gemcitabine, taxanes, or other regimens listed in the National Comprehensive Cancer Network [NCCN] guidelines)
  • Radiographic progression:

    • Patients with GBM/AA must have radiographic progression based on RANO criteria
    • 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."
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) 0 or 1. For patients with NSCLC with leptomeningeal metastases, ECOG 2 is also acceptable
  • Registration - Inclusion Criteria Specific to Dose Expansion Cohorts
  • Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort:

    • Previous treatments: Patients must have been previously treated with radiation and temozolomide
    • Radiographic progression: Patients with GBM/AA must have radiographic progression based on RANO criteria
    • Measurable disease
    • Performance status: ECOG 0 or 1 for patients with GBM/AA
  • Brain Tumor Penetration (BTP) Cohort:

    • Previous treatments: Patients must have been previously treated with radiation and temozolomide
    • Radiographic progression: Patients with GBM/AA must have radiographic progression based on RANO criteria
    • Therapeutic surgical resection of GBM/AA required as part of routine clinical care
    • Performance status: ECOG 0 or 1
  • Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort:

    • Previous treatments: Patients must have had either:

      • No prior treatment with an EGFR TKI, or
      • Previous EGFR TKI treatment (e.g. gefitinib, erlotinib, afatinib, or osimertinib) followed by central nervous system (CNS) disease progression without extra-CNS progression
    • Radiographic progression: Patients must have new or radiographic progression of leptomeningeal metastases. Positive confirmation of CSF cytology is both necessary and sufficient to define the presence of leptomeningeal metastases for patients in this study
    • For the NSCLC LM expansion cohort, patients must have both positive confirmation of CSF cytology and at least one site of leptomeningeal disease that can be assessed by magnetic resonance imaging (MRI) and which is suitable for repeat assessments as per the investigator's discretion
    • Performance Status: ECOG 0, 1, or 2
  • Registration - Inclusion Criteria Common to Dose Escalation and Dose Expansion Cohorts:
  • Ability to understand and the willingness to sign a written informed consent document
  • Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)
  • Leukocytes >= 3.0 x 10^9/L (obtained =< 14 days prior to registration)
  • Absolute neutrophil count >= 1.5 x 10^9/L (obtained =< 14 days prior to registration)
  • Platelets >= 100 x 10^9/L (obtained =< 14 days prior to registration)
  • International normalized ratio (INR) =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration)

    • 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
  • aPTT =< 1.5 x ULN (obtained =< 14 days prior to registration)

    • 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
  • Total bilirubin =< 1.5 x ULN and < 3 mg/dL for patients with Gilbert's disease (obtained =< 14 days prior to registration)
  • 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)
  • Creatinine =< 1.5 x ULN or estimated glomerular filtration rate (estimated glomerular filtration rate [eGFR]) >= 60 mL/minute (obtained =< 14 days prior to registration)
  • Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
  • Provision of signed and dated written informed consent prior to any study specific procedures, sampling, and analyses
  • Willingness to provide mandatory blood specimens and mandatory tissue specimens for correlative research
  • 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)
  • 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
  • Must be willing to take light-protective measures during the study and for 2 weeks after their last dose of WSD0922-FU
  • Must have a minimum life expectancy of >= 3 months
  • Must be stable on no more than 2 mg of dexamethasone (or equivalent steroids) per day. Steroid dose should not be adjusted during cycle 1 of therapy
  • 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. Drug-drug interactions (DDI) with proton pump inhibitor (PPI), H2 blockers or antacids have not been assessed; therefore it is suggested to avoid taking those drugs together with WSD0922-FU
  • Strong inducers and strong inhibitors of CYP3A should be discontinued at least 14 days prior to registration

Exclusion Criteria:

  • Registration - Exclusion Criteria for Dose Escalation and Dose Expansion
  • 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:

    • Pregnant persons
    • Nursing persons
    • Persons of childbearing potential who are unwilling to employ adequate contraception
  • Any of the following prior therapies:

    • Any cytotoxic chemotherapy or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen =< 14 days prior to registration
    • In patients with NSCLC, treatment with an EGFR TKI (e.g., erlotinib, gefitinib, afatinib or osimertinib) within 8 days or approximately 5 x half-life, whichever is the longer, prior to registration (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)
    • Radiation therapy to the brain =< 12 weeks prior to registration
    • 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.) or prior treatment with bevacizumab
    • Received prior systemic biologic therapy (CAR-T, anti-PD-1 / anti-PD-L1, anti-CTLA-4, etc.) within 28 days prior to registration.
  • 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
  • Subjects who are human immunodeficiency virus (HIV), hepatitis virus B (HBV), and/or hepatitis virus C (HCV) positive
  • Uncontrolled inter-current illness including, but not limited to:

    • Symptomatic CNS complications that require urgent neurosurgical or medical (e.g. mannitol) intervention
    • Seizures requiring a change in anti-epileptic medications (addition of new anti-epileptic or increase in dose) =< 2 weeks of registration
    • Known intracranial hemorrhage which is unrelated to tumor
    • Significant medical or psychiatric illness that would interfere with compliance and ability to tolerate treatment as outlined in the protocol
    • Illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • 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
  • Any of the following cardiac criteria:

    • A marked baseline prolongation of QT/corrected QT (QTc) interval
    • (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
    • A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome)
    • The use of concomitant medications that prolong the QT/QTc interval
  • Patients confirmed to have a cis double mutation (Del19/T790M or L858R/T790M) or cis triple mutation (Del19/T790m/C797S or L858R/T790M/C797S)
  • 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
  • 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
  • Inadequate bone marrow reserve or organ function
  • Patients with NSCLC LM who are unable to undergo collection of CSF

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04197934


Locations
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United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Referral Office    855-776-0015    mayocliniccancerstudies@mayo.edu   
Principal Investigator: Maciej M. Mrugala, MD         
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Clinical Trials Referral Office    855-776-0015    mayocliniccancerstudies@mayo.edu   
Principal Investigator: Kurt A. Jaeckle, MD         
United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015    mayocliniccancerstudies@mayo.edu   
Principal Investigator: Sani H. Kizilbash, MD         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Sani H Kizilbash Mayo Clinic
Additional Information:
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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT04197934    
Other Study ID Numbers: MC1914
NCI-2019-07825 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1914 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: December 13, 2019    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioma
Neoplasms
Glioblastoma
Astrocytoma
Neoplasms, Second Primary
Carcinoma, Non-Small-Cell Lung
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases