| General information |
| Database: | DB00590 |
| Objective: | When surgery and radiation are no longer treatment options, salvage systemic therapy has been used for recurrent meningiomas with little compelling evidence to suggest effectiveness. |
| Authors: | Raizer JJ, et al |
| Title: | a phase II trial of PTK787/ZK 222584 in recurrent or progressive radiation and surgery refractory meningiomas. |
| Journal: | J Neurooncol |
| Year: | 2014 |
| PMID: | 24449400 |
| Trial Design |
| Clinical Trial Id: | NCT00348790 |
| Agent: | PTK787/ZK 222584
|
| Target: | Vascular endothelial growth factor receptor 2
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | meningioma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II trial |
| Key Patients Feature: | Inclusion and exclusion criteria included the following. Histologically proven meningioma of any grade withevidence of tumor progression on cranial imaging or metastatic disease. All imaging was revietheyd by the treatingphysician to confirm measurable tumor progression of[15 %, if progression could not be confirmed the patient was noteligible. Patients with neurofibromatosis type 2 (NF2) andintracranial hemangiopericytoma were also eligible. NF2patients had to have stable disease of other coexisting CNStumors (i.e. schwannomas) for [6 months prior to studyentry. Patients had to be[18 years old with a life expectancy[12 weeks and a Karnofsky performance status ofC60. Patients were required to have measurable disease byMRI of the brain and on a stable dose of steroids for[5 days. Patients having undergone recent resection ofrecurrent or progressive tumor had to be[4 weeks fromsurgery with evaluable residual disease. Patients needed tobe C4 weeks from the completion of external beam radiation therapy but prior RT was not required. Progressive disease after RT required disease outside the radiationfield or surgical documentation. There was no limitationon the number of prior therapies. Patients had to be[4 weeks from cytotoxic chemotherapy or other investigational agents and[2 weeks for noncytotoxic or biologic systemic therapies. Laboratory tests were performedwithin 14 days of registration and required an ANCC2, 000/mm3, platelets C100, 000/mm3, and hemoglobinC10 gm/dL; PT, INR and PTT B1.5 times upper limit ofnormal (ULN); SGOT, SGPT and bilirubin2 times theULN and bilirubin 1.5 9 BULN; creatinine1.5 mg/dLbefore starting treatment. Patient¡¯s had to have a negativeurine protein based on dip stick, if 1 result then a 24hurine collection was required to document a urinary protein B 500 mg/dL. Women of childbearing potentialrequired a negative pregnancy test. Patients on an enzymeinducing antiepileptic drug (EIAED) had to be placed onnonEIAED before beginning treatment with a 2weekwash out period. Patients on other drugs that affectedhepatic metabolism (i.e. coumadin) also required a 2weekwash out period. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts were treated with the oral multifunctional tyrosine kinase inhibitor PTK787/ZK 222584 (PTK787) at a dose of 500 mg twice a day. Each treatment cycle was 4 weeks with MRI done every 8 weeks. |
| Primary End Point: | 6month progression free survival (PFS6) |
| Secondary End Point: | overall survival (OS), and objective radiographic response rate (ORR) |
| Patients Number: | 25 |
| Trial Results |
| DLT_MTD: | PTK787 was modestly toxic at the dose of 500 mg administered twice per day. |
| Objective Response Rate: | Best response in the 22 evaluable patients was stable disease in 15 (68.2 %). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 6.5 months in Grade II patients. grade III patients had a median PFS of 3.6 months |
| Median OS A vs. C: | 26.0 months in Grade II patients. grade III patients had a OS 23 months. |
| Adverse Event(agent arm): | Predominant PTK787 related toxicities included fatigue (60 %), hypertension (24 %) and elevated transaminases (24 %). |
| Conclusions: | Activity as determined by PFS6 suggests that targeting PDGFVEGF pathway warrants further investigation. |