Cabozantinib for Patients With Recurrent or Progressive Meningioma

Meningioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05425004
• Other study ID #: 2020-KOT-002
• Status: Recruiting
• Phase: Phase 2
• Start date: May 27, 2022
• Est. completion date: May 2028

Study information

• Verified date: March 2024
• Source: Baptist Health South Florida
• Contact: Rupesh R Kotecha, M.D.
• Phone: (786) 596-2000
• Email: rupeshk[@]baptisthealth.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: May 2028
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

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

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

3. Karnofsky Performance Status = 50.

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.

5. Adequate renal function: = 30 ml/min according to the Cockcroft-Gault formula.

6. Adequate hepatic function including:

1. Total bilirubin = 1.5 x upper limit of normal (ULN).

2. Aspartate transaminase (AST) = 3 x ULN without liver metastasis.

3. Alanine transaminase (ALT) = 3 x ULN without liver metastasis.

4. AST or ALT = 5 x 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

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

9. 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.

10. 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.

11. Serum albumin = 2.8 g/dL.

12. Prothrombin time (PT)/International Normalized Ratio (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 the 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) with 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.

9. History of congenital QT syndrome.

10. Correct QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 14 days of study registration. 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.

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

12. Urine Protein-to-Creatinine ratio (UPCR) >1 mg/mg or 24-hour urine protein > 1 gram.

13. History of bleeding diathesis or significant unexplained coagulopathy (e.g., in the absence of anticoagulation).

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

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

16. Active infection requiring parenteral antibiotic therapy.

17. History of either positive hepatitis C virus (HCV) RNA viral load or detectable anti-HCV antibody; hepatitis B virus (HBV) infection with HBV surface antigen detection and/or positive HBV DNA viral load.

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

19. Known hypersensitivity to cabozantinib or any component in formulation.

20. Inability to swallow capsules, known intolerance to cabozantinib or its excipients, known malabsorption syndrome, or other conditions which impair intestinal absorption.

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

22. 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.

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

1. Cardiovascular disorders:

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

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

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

5. 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.

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

7. 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.

8. 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.

24. 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.

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

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

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

2. Uncompensated/symptomatic hypothyroidism.

3. Moderate to severe hepatic impairment (Child-Pugh B or C).

27. 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

Related Conditions & MeSH terms

• Meningioma

Intervention

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, hydroxypropyl 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.

Locations

Country	Name	City	State
United States	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Baptist Health South Florida	Exelixis

Country where clinical trial is conducted

United States, 

References & Publications (19)

Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, Cicin I, Merle P, Chen Y, Park JW, Blanc JF, Bolondi L, Klumpen HJ, Chan SL, Zagonel V, Pressiani T, Ryu MH, Venook AP, Hessel C, Borgman-Hagey AE, Schwab G, Kelley RK. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018 Jul 5;379(1):54-63. doi: 10.1056/NEJMoa1717002. — View Citation

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Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Geczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ; METEOR Investigators. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. doi: 10.1056/NEJMoa1510016. Epub 2015 Sep 25. — View Citation

Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DYC, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ; METEOR investigators. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-927. doi: 10.1016/S1470-2045(16)30107-3. Epub 2016 Jun 5. — View Citation

Choueiri TK, Hessel C, Halabi S, Sanford B, Michaelson MD, Hahn O, Walsh M, Olencki T, Picus J, Small EJ, Dakhil S, Feldman DR, Mangeshkar M, Scheffold C, George D, Morris MJ. Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update. Eur J Cancer. 2018 May;94:115-125. doi: 10.1016/j.ejca.2018.02.012. Epub 2018 Mar 20. Erratum In: Eur J Cancer. 2018 Nov;103:287. — View Citation

Escudier B, Powles T, Motzer RJ, Olencki T, Aren Frontera O, Oudard S, Rolland F, Tomczak P, Castellano D, Appleman LJ, Drabkin H, Vaena D, Milwee S, Youkstetter J, Lougheed JC, Bracarda S, Choueiri TK. Cabozantinib, a New Standard of Care for Patients With Advanced Renal Cell Carcinoma and Bone Metastases? Subgroup Analysis of the METEOR Trial. J Clin Oncol. 2018 Mar 10;36(8):765-772. doi: 10.1200/JCO.2017.74.7352. Epub 2018 Jan 8. — View Citation

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Raizer JJ, Fitzner KA, Jacobs DI, Bennett CL, Liebling DB, Luu TH, Trifilio SM, Grimm SA, Fisher MJ, Haleem MS, Ray PS, McKoy JM, DeBoer R, Tulas KM, Deeb M, McKoy JM. Economics of Malignant Gliomas: A Critical Review. J Oncol Pract. 2015 Jan;11(1):e59-65. doi: 10.1200/JOP.2012.000560. Epub 2014 Dec 2. — View Citation

Rogers CL, Won M, Vogelbaum MA, Perry A, Ashby LS, Modi JM, Alleman AM, Galvin J, Fogh SE, Youssef E, Deb N, Kwok Y, Robinson CG, Shu HK, Fisher BJ, Panet-Raymond V, McMillan WG, de Groot JF, Zhang P, Mehta MP. High-risk Meningioma: Initial Outcomes From NRG Oncology/RTOG 0539. Int J Radiat Oncol Biol Phys. 2020 Mar 15;106(4):790-799. doi: 10.1016/j.ijrobp.2019.11.028. Epub 2019 Nov 29. — View Citation

Shih KC, Chowdhary S, Rosenblatt P, Weir AB 3rd, Shepard GC, Williams JT, Shastry M, Burris HA 3rd, Hainsworth JD. A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma. J Neurooncol. 2016 Sep;129(2):281-8. doi: 10.1007/s11060-016-2172-3. Epub 2016 Jun 16. — View Citation

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS)	Proportion of participants who from start of treatment to 6-months are free from objective tumor progression or death from any cause.	6 months
Secondary	Objective response rate (ORR)	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 years
Secondary	Overall survival (OS)	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.	2 years
Secondary	Proportion of participants with adverse events	Proportion of participants who develop adverse events assessed by CTCAE v5.0 criteria.	2 years
Secondary	Quality of life (QOL)	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).	2 years

External Links

•   Miami Cancer Institute