Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas

NCT01140568 | Completed Phase 2 Results DMC

• 1 other identifier: 091728
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the survival, disease response, and side effects of Tasigna® (nilotinib) in patients who have malignant gliomas and are positive for Platelet Derived Growth Factor Receptor (PDGFR) amplification. This study is designed to test the hypothesis that patients with malignant gliomas with PDGFR amplification are sensitive to PDGFR kinase inhibitors.

Conditions

Glioma

Keywords

glioma; PDGFR; kinase; inhibitor; malignant; nilotinib

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Had 6-month Progression-free Survival.

  Progression was defined by McDonald Criteria: A 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

  6 months

Secondary Outcomes (1)

• Overall Response Rate

  5 years

Study Arms (1)

nilotinib

EXPERIMENTAL

Patients will take nilotinib twice daily at the standard dose of 400mg taken by mouth twice a day until disease progression or development of unacceptable side effects.

Drug: nilotinib

Interventions

nilotinib DRUG

400mg po (orally) BID (twice daily)

Also known as: Tasigna

nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide written informed consent prior to participation in the study and any related procedures being performed.
• Participants must have agreed to and signed an authorization for the release of their protected health information.
• Subjects must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary.
• Participants must have a life expectancy of at least 8 weeks.
• Patients greater than 18 years of age.
• Histologically documented diagnosis of proven glioblastoma (GBM), or anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and anaplastic mixed oligoastrocytoma (AMO). Patients are eligible if the original local pathology was lower-grade glioma. Pathology will be read centrally to confirm diagnosis.
• Documentation of amplified PDGFRA by fluorescent in-situ hybridization (FISH), colorimetric in-situ hybridization (CISH), or quantitative PCR from tumor tissue (=\>3 copy number). Availability of unstained paraffin slides or the paraffin block of pretreatment baseline tissue is required for eligibility and for molecular analysis and would help to identify molecular predictors of outcome (all patients).
• Participants must have a Karnofsky Performance Status (KPS) ≥ 60.
• Adequate end organ function, defined as the following:
• Hematology:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9.0 g/dL
• White blood cell (WBC) count ≥ 3.0 x 109/L
• Biochemistry:

You may not qualify if:

• Patients who received PDGFR inhibitors (imatinib, sunitinib, nilotinib, etc.) previously are excluded (patients who received PDGFR antibody based treatment however are allowed).
• History of intratumoral or peritumoral hemorrhage if deemed significant by the treating physician.
• For patients requiring anticoagulation therapy, only therapeutic low molecular weight heparin or factor Xa inhibitors are permitted.
• Due to the potential interaction between nilotinib and enzyme-inducing anti-epileptic drugs (EIAED), only patients on non-enzyme inducing anti-epileptic drugs (NEIAED) or on no anti-epileptic drugs are eligible.
• Patient is \< 3 years free of another primary malignancy except: if the other primary malignancy is not currently clinically neither significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
• Female patients who are pregnant or breast-feeding, or intends to become pregnant during the study.
• Any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
• Patient has a rare hereditary problem of galactose intolerance, severe lactase deficiency or of glucose-galactose malabsorption.
• Patients with any disease that will obscure toxicity or dangerously alter drug metabolism.
• Patient with electrolyte abnormality (e.g., hypokalemia, hypomagnesemia, hypophosphatemia, hyperkalemia, hypocalcemia, hyponatremia) unless the level can be corrected to normal levels prior to initiating study drug.
• Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
• Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea) prior to study entry, unless the disease is rapidly progressing.
• Concomitant use of any anti-cancer therapy or radiation therapy, or any other investigational agent.
• Impaired cardiac function including any of the following:
• Congenital long QT syndrome or a known family history of long QT syndrome;

Sponsors & Collaborators

• David Piccioni, M.D., Ph.D: lead
• Novartis: collaborator

Study Sites (1)

The Rebecca and John Moores UCSD Cancer Center

La Jolla, California, 92093, United States

Location

Related Publications (1)

• Piccioni D, Juarez TM, Kesari SL, Rose L, Nomura N, Kesari S. Phase II trial of nilotinib in PDGFR-alpha-enriched recurrent high-grade gliomas. Neurooncol Adv. 2025 Jul 10;7(1):vdaf150. doi: 10.1093/noajnl/vdaf150. eCollection 2025 Jan-Dec.

  PMID: 40709015 DERIVED

MeSH Terms

Conditions

Glioma

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Lara Rose
• Organization: UCSD - Moores Cancer Center

ljrose@ucsd.edu

858-822-6575

Study Officials

• David Piccioni, MD, PhD

  University of California Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Clinical Professor

Study Record Dates

• First Submitted: June 8, 2010
• First Posted: June 9, 2010
• Study Start: April 21, 2010
• Primary Completion: October 5, 2016
• Study Completion: January 1, 2019
• Last Updated: May 5, 2020
• Results First Posted: April 24, 2020

Record last verified: 2020-04

Locations

US (1)