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Cabozantinib for Patients With Recurrent or Progressive Meningioma

Sponsor
Baptist Health South Florida (Other)
Overall Status
Recruiting
CT.gov ID
NCT05425004
Collaborator
Exelixis (Industry)
24
Enrollment
1
Location
1
Arm
23.1
Anticipated Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase II Study of Cabozantinib for Patients with Recurrent or Progressive Meningioma

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
24 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Cabozantinib for Patients With Recurrent or Progressive Meningioma
Actual Study Start Date :
May 27, 2022
Anticipated Primary Completion Date :
Apr 28, 2023
Anticipated Study Completion Date :
Apr 28, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cabozantinib

Participants will self-administer cabozantinib 60 mg at the same time daily by mouth on a continuous 28-day schedule. Participants will continue to take this medication as long as they are deriving benefit from it without significant treatment-related toxicities.

Drug: Cabozantinib
Cabozantinib tablets are supplied as film coated tablets containing cabozantinib malate equivalent to 20 mg and 60 mg of cabozantinib and contain microcrystalline cellulose, lactose anhydrous, hydoxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate and Opadry® yellow. The 60 mg tablets are oval and the 20 mg tablets are round. Doses of 40 mg will comprise two 20-mg tablets.
Other Names:
  • XL184
  • Cometriq
  • Cabometyx
  • BMS907351

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression free survival (PFS) [6 months]

      Proportion of participants who from start of treatment to 6-months are free from objective tumor progression or death from any cause.

    Secondary Outcome Measures

    1. Objective response rate (ORR) [2 years]

      Proportion of participants with confirmed complete response (CR) or partial response (PR) assessed by Immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria, relative to the total population of patients enrolled who initiate therapy.

    2. Overall survival (OS) [5 years]

      Overall Survival (OS): duration of time from start of treatment until death from any cause. Patients lost-to follow up will be censored at last valid assessment.

    3. Proportion of participants with adverse events [2 years]

      Proportion of participants who develop adverse events assessed by CTCAE v5.0 criteria.

    4. Quality of life (QOL) [2 years]

      QOL will be measured by Functional Assessment of Cancer Therapy-Brain (FACT-Br) Version 4. The FACT-Br questionnaire is a 23-item survey, participants then rate each item on a Likert scale from 0 "not at all" to 4 "very much", and overall, higher ratings are suggestive of better quality of life. QOL will be assessed at the baseline, day 1 of every cycle (treatment days, every 4 weeks on 28-day cycle, and every 6 weeks on 42-day cycle).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Histologic (preferred) or radiologic diagnosis of meningioma. All WHO grades (I, II and III) are allowed.

    2. All patients must have developed recurrent disease or progressive disease after receiving standard therapy (eg, radiation or surgery) >6 months ago or have been deemed ineligible to receive these therapies.

    3. Karnofsky Performance Status ≥50 (Appendix 1)

    4. Adequate Hematologic Function

    (1) Absolute Neutrophil Count ≥ 1.5 x 10^9 / L without granulocyte colony-stimulating factor support.

    (2) Platelet Count ≥ 100 x 10^9 / L without transfusion. (3) Hemoglobin ≥ 9 g/dL without transfusion within 7 days prior to screening assessment.

    1. Adequate Renal Function ≥ 30 ml/min according to the Cockcroft-Gault formula (Appendix
      1. Adequate Hepatic Function including:

    (1) Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (2) AST ≤ 3 x upper limit of normal (ULN) without liver metastasis (3) ALT ≤ 3 x upper limit of normal (ULN) without liver metastasis (4) AST or ALT ≤ 5 x upper limit of normal (ULN) for patients with liver metastasis (5) Patients with known Gilbert's syndrome may be included if total bilirubin ≤ x 3 ULN 7. Patients must have measurable disease by iRANO criteria (Section 13.2.2.1) 8. Women of childbearing potential must have negative serum pregnancy testing at screening.

    All women will be considered childbearing potential unless meeting criteria including:

    (1) Achieved post-menopausal status as defined by cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have follicular stimulation hormone showing postmenopausal state. Women who have been amenorrhoeic for ≥12 months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anorexia, low body weight, ovarian suppression, anti-estrogen therapy or other medically inducible reasons.

    (2) Documented hysterectomy or bilateral oophorectomy surgery (3) Medically confirmed ovarian failure (4) Sexually active participants and their partners must agree to use medically accepted methods of contraception during the study and for 4 months after discontinuing study treatment (Section 11.4).

    1. Recovery of baseline CTCAE v5.0 Grade ≤1 toxicity related to prior study treatments unless adverse events are clinically non-significant per investigator's discretion and/or stable on supportive therapy if needed.

    2. Patients must be willing and able to comply with trial protocol. This includes adhering to the treatment plan, scheduled visits, laboratory and other study procedures.

    3. Serum albumin ≥ 2.8 g/dl 12. (PT)/INR or partial thromboplastin time (PTT) test < 1.3x the laboratory ULN

    Exclusion Criteria:

    1. Prior treatment with cabozantinib

    2. Patients <18 years old

    3. Patients who are pregnant or breast-feeding.

    4. Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

    5. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.

    6. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.

    7. Ejection Fraction (EF) ≤50% by echocardiogram (ECHO). Multi-gated acquisition scan (MUGA) should be obtained to estimate EF if quality of ECHO is insufficient.

    8. Prior history of hypertensive encephalopathy at any time 10. History of congenital QT syndrome. 11. Corrected QT interval calculated by the Fridericia formula (QTcF) >500 ms within 14days of study registration (Appendix 6). If initial QTcF is >500 ms, two additional EKGs separated by at least 3 minutes should be performed, and if average of these consecutive results is QTcF is ≤ 500 ms, patient is eligible.

    9. Unstable cardiac arrhythmia within 6 months prior to study registration date.

    10. Urine Protein-to-Creatinine ratio (UPCR) >1 mg/mg or 24-hour urine protein > 1 gram (Appendix 5) 14. History of bleeding diathesis or significant unexplained coagulopathy (eg, in the absence of anticoagulation).

    11. Clinical signs or symptoms of gastrointestinal obstruction requiring parenteral hydration, nutrition or feeding tube.

    12. Uncontrolled effusion management (pleural effusion, pericardial effusion or ascites) requiring recurrent drainage procedures.

    13. Active infection requiring parenteral antibiotic therapy. 18. History of either positive HCV RNA viral load or detectable anti-HCV antibody; HBV infection with HBV surface antigen detection and/or positive HBV DNA viral load.

    14. Serious non-healing wound, ulcer, or bone fracture requiring intervention within 28 days prior to study registration date.

    15. Known hypersensitivity to cabozantinib or any component in formulation. 21. Inability to swallow capsules, known intolerance to cabozantinib or its excipients, known malabsorption syndrome, or other conditions which impair intestinal absorption.

    16. Other severe acute or chronic medical conditions, which may increase study risk per treating investigator's discretion.

    17. Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:

    1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).

    2. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.

    1. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

    2. Cardiovascular disorders:

    3. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.

    4. Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.

    5. Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.

    6. Subjects with a diagnosis of incidental, sub-segmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion #6) for at least 1 week before first dose of study treatment.

    7. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:

    8. The subject has evidence of any concurrent malignancy invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.

    9. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.

    Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.

    1. Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.

    2. Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease from another malignancy.

    3. Other clinically significant disorders that would preclude safe study participation.

    4. Serious non-healing wound/ulcer/bone fracture.

    5. Uncompensated/symptomatic hypothyroidism.

    6. Moderate to severe hepatic impairment (Child-Pugh B or C). 28. Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Miami Cancer Institute at Baptist Health, Inc Miami Florida United States 33176

    Sponsors and Collaborators

    • Baptist Health South Florida
    • Exelixis

    Investigators

    • Principal Investigator: Rupesh R Kotecha, Miami Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Baptist Health South Florida
    ClinicalTrials.gov Identifier:
    NCT05425004
    Other Study ID Numbers:
    • 2020-KOT-002
    First Posted:
    Jun 21, 2022
    Last Update Posted:
    Jun 21, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Baptist Health South Florida
    Meningioma
    central nervous system tumors
    Recurrent meningioma
    Progression meningioma
    Additional relevant MeSH terms:
    Meningioma

    Study Results

    No Results Posted as of Jun 21, 2022