Phase 2
N=30
Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy
Childhood High-grade Cerebellar Astrocytoma · Childhood High-grade Cerebral Astrocytoma · Recurrent Childhood Anaplastic Astrocytoma · Recurrent Childhood Anaplastic Oligoastrocytoma · Recurrent Childhood Anaplastic Oligodendroglioma
Bottom Line
View on ClinicalTrials.gov: NCT00679354 ↗Enrolled (actual)
30
Serious AEs
27.6%
Results posted
Feb 2014
Primary outcome: Primary: Objective Response to Cilengitide — 1; 23 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- cilengitide (Drug); laboratory biomarker analysis (Other); pharmacological study (Other)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Oct 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Objective Response to Cilengitide |
1; 23 | — |
| SECONDARY Time to Tumor Progression (TTP) |
28 | — |
| SECONDARY Time to Treatment Failure (TTF) |
28 | — |
| SECONDARY Time to Death (TTD) |
172 | — |
| SECONDARY Rate of Toxicity, Especially That of Symptomatic Intratumoral Hemorrhage (ITH) Assessed by Common Terminology Criteria for Adverse Events Version 4.0 |
6.9 | — |
| SECONDARY Pharmacokinetic Parameter of Cilengitide in Plasma: Volume of Central Compartment (Vc) |
6.20 | — |
| SECONDARY Pharmacokinetic Parameter of Cilengitide in Plasma: Elimination Rate Constant (Ke) |
0.58 | — |
| SECONDARY Pharmacokinetic Parameter of Cilengitide in Plasma: Half-life (t1/2) |
1.26 | — |
| SECONDARY Pharmacokinetic Parameter of Cilengitide in Plasma: Systemic Clearance (Cl) |
3.84 | — |
| SECONDARY Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by AUC |
0.00 | 1.000 |
| SECONDARY Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by Systemic Clearance |
0.56 | 0.057 |
| SECONDARY Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by AUC |
-0.22 | 0.495 |
| SECONDARY Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by Systemic Clearance |
-0.48 | 0.114 |
Summary
This phase II trial studies how well cilengitide works in treating younger patients with recurrent or progressive high-grade glioma that has not responded to standard therapy. Cilengitide may stop the growth of tumor cells by blocking blood flow to the tumor.
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed primary central nervous system (CNS) high-grade glioma, including any of the following:
- Glioblastoma multiforme
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- High-grade astrocytoma not otherwise specified (i.e., anaplastic ganglioglioma, anaplastic mixed glioma, or anaplastic mixed glioneuronal tumors)
- No diffuse pontine gliomas, gliomatosis cerebri, and primary spinal cord high-grade astrocytoma
- Gliosarcoma
- Recurrent or progressive disease that is refractory to standard therapy
- Radiographically documented measurable disease
- Lesion must be at least twice the thickness of the image from which it is derived (e.g., 10 mm for a 5 mm slice thickness)
- No diffuse pontine gliomas
- No evidence of prior CNS bleeding
- Karnofsky performance status (PS) 50-100% (patients > 16 years of age)
- Lansky PS 50-100% (patients = = 8 weeks
- Absolute neutrophil count (ANC) >= 1,000/μL
- Platelet count >= 100,000/μL (transfusion independent)
- Hemoglobin >= 8.0 g/dL (red blood cell [RBC] transfusions allowed)
- Creatinine clearance or radioisotope glomerular filtration rate >= 70mL/min OR serum creatinine based on age/gender as follows:
- 0.4 mg/dL (1 month to = 16 years of age)
- Total bilirubin = 94%, if determination is clinically indicated
- Seizure disorder is allowed provided it is well-controlled with anticonvulsants
- No uncontrolled infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Recovered from all prior therapy
- No more than two prior treatments for high-grade glioma (i.e., one initial treatment and one treatment for relapse)
- More than 2 weeks since prior myelosuppressive chemotherapy (>= 6 weeks for nitrosoureas)
- At least 1 week since prior non-myelosuppressive chemotherapy, immunotherapy, or biologic therapy
- At least 2 weeks since prior local palliative radiotherapy (i.e., small port) to a symptomatic non-target lesion only
- At least 3 months since prior craniospinal radiotherapy
- At least 6 weeks since prior substantial bone marrow radiotherapy
- At least 6 months since prior allogeneic stem cell transplant (SCT) or rescue
- Patients who have undergone prior allogeneic SCT and who have graft-versus-host disease (GVHD) must have controlled GVHD that is = 3 weeks for pegfilgrastim [Neulasta®])
- No other concurrent anticancer therapy, including chemotherapy or immunomodulating agents
- No other concurrent experimental agents or therapies
- No concurrent alternative or complimentary therapies
- No concurrent homeopathic medicines
- No concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (aspirin)
- No concurrent steroids as anti-emetics
- Concurrent steroids for treatment of increased intracranial pressure allowed if on a stable or decreasing dose for >= 1 week before study entry
- Concurrent radiotherapy to localized painful lesions allowed provided >= 1 measurable lesion is not irradiated
Data sourced from ClinicalTrials.gov (NCT00679354). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.