A Study of Intraventricular Liposomal Encapsulated Ara-C (DepoCyt) in Patients With Recurrent Glioblastoma

NCT01044966 | Terminated Phase 1 Results DMC

• 2 other identifiers: 3542R01FD003542-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Current treatments for Glioblastoma Multiforme (GBM), the most common and malignant primary brain tumor are inadequate and as such, the median survival for most patients with GBM is on the order of months, even after cytoreductive surgery, radiation and chemotherapy. This study aims to develop a new treatment for GBM by suppressing glial progenitor cells that surround the ventricular system in patients with these aggressive tumors because it is these regions that appear to act as an incubator for future recurrences resulting in patient death. Considering the lack of significant treatment options for patients with this uniformly fatal disease, this is an important translational clinical study to perform.

Conditions

Glioblastoma Multiforme; Glioma; Astrocytoma; Brain Tumor

Keywords

Glioblastoma; Subventricular; gliomagenesis; temozolomide; depocyt

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

  The type and number of adverse events will be recorded and reported by the number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  52 weeks

Secondary Outcomes (4)

• Proportion of Patients With Recurrent GBM Treated With ITV DepoCyt in Combination With Oral Temozolomide Who Are Progression-free at 16 Weeks.

  16 weeks

• Progression Free Survival

  At 6 months

• Response Rate of Drug Treatment

  52 weeks

• Quality of Life Outcomes Measurement

  52 weeks

Study Arms (1)

ITV DepoCyt + Temozolomide

EXPERIMENTAL

Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues. Oral metronomic Temozolomide dosing of 75 mg/m2 daily for 21 days followed by 7 days off will be given throughout the Induction, Consolidation, and Maintenance Phases of the ITV DepoCyt described above.

Drug: ITV DepoCyt + Temozolomide

Interventions

ITV DepoCyt + Temozolomide DRUG

Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous oral dosing), followed by 7 days off in a 28 day cycle as a once daily dosing regimen.

Also known as: Intrathecal liposomal Ara-C (DepoCyt), Temozolomide (Temodar)

ITV DepoCyt + Temozolomide

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age Patients must be at least 18 years of age but no older than 85 years.
• Prior therapy Patients must have had an initial diagnosis of "malignant glioma" (WHO grade III or IV) and failed initial surgical resection followed by standard adjuvant therapy including external beam radiotherapy to a 2cm margin of 60 Gy, and standard temozolomide chemotherapy of 150 to 200 mg per square meter for 5 days during each 28-day cycle prior to "recurrence." Patients must not have received more than one other systemic or ITV adjuvant chemotherapy regimen in addition to temozolomide prior to enrollment, not including intracavitary Gliadel wafer placement. Prior Gliadel wafer placement is not a contradiction to patient enrollment in this trial.
• Performance Status Patients must have Karnofsky performance status (KPS) of ≥ 60%.
• Recovery from Prior Therapy Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy, prior to entering this study and must be without significant systemic illness (e.g. infection unresponsive to treatment after 7 days). Such that they are healthy enough to safely undergo tumor biopsy and Ommaya reservoir placement. Patients must not have received any systemic therapy for recurrent disease within 3 weeks (6 weeks if a nitrosourea), or irradiation within 8 weeks prior to treatment on this study.
• Hematologic Status Patients must have a platelet count \> 75,000/mm3 and ANC \> 1500/mm3 within 72 hours prior to ITV DepoCyt treatment.
• Hepatic and Renal Status Patients must have adequate liver function (total bilirubin \< 2.0 mg%; ALT, and AST \< 4 times normal); adequate renal function (serum creatinine \<1.6 mg, and BUN \< 22); normal serum electrolytes (sodium, potassium, calcium, magnesium, and phosphorus).
• Informed Consent (See Appendix) All patients or their legal guardians must sign a document of informed consent indicating their awareness of the investigational nature and the risks of this study.

You may not qualify if:

• Patients younger than 18 or older than 85 years of age.
• Patients with histological diagnoses other than recurrent GBM.
• Patients with a Karnofsky performance status (KPS) \< 60%.
• Patients that have received more than one other systemic or ITV adjuvant chemotherapy regimen in addition to temozolomide, not including intracavitary Gliadel wafer placement.
• Patients concurrently receiving other therapies (either brachytherapy or systemic) designed specifically to treat the recurrent GBM.
• Patients within 8 weeks of receiving stereotactic or external beam irradiation.
• Patients with a platelet count \< 75,000/mm3 and ANC \< 1500/mm3 within 72 hours prior to ITV DepoCyt and/or oral temozolomide treatment.
• Patients with liver dysfunction (total bilirubin \> 2.0 mg%; ALT, and AST \> 4 times normal).
• Patients with renal dysfunction (serum creatinine \>1.6 mg, and BUN \> 22).
• Patients with abnormal serum electrolytes (sodium, potassium, calcium, magnesium, and phosphorus).
• Patients with contraindications to having placement of a ventricular access device such as Ommaya reservoir.
• Patients with clinical and/or neuroradiographic evidence of hydrocephalus or increased intracranial pressure.
• Patients with signs and symptoms of systemic infection precluding them from receiving chemotherapy or prohibiting Ommaya reservoir placement.
• Pregnant and breast feeding women will be excluded. All other women of childbearing years must have a negative serum pregnancy test.
• Patients with a ventricular-peritoneal or ventricular-atrial shunt.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Links

• (Link to contact Dr. Frankel at Medical University of South Carolina)

MeSH Terms

Conditions

Glioblastoma; Glioma; Astrocytoma; Brain Neoplasms

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The enrollment of patients in this study was limited due to a number of factors including: rareness of disease, poor KPS upon disease recurrence, the availability of subsequent FDA approved drugs (Avastin) after study initiation.

Results Point of Contact

• Title: Dr. Bruce Frankel
• Organization: Medical University of South Carolina

frankel@musc.edu

8437922052

Study Officials

• Bruce M Frankel, MD

  Medical University of South Carolina, Dept. of Neurosciences, Division of Neurosurgery

  PRINCIPAL INVESTIGATOR

• Gustavo Leone

  Medical University of South Carolina, Hollings Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2010
• First Posted: January 8, 2010
• Study Start: September 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: September 1, 2014
• Last Updated: February 12, 2019
• Results First Posted: February 12, 2019

Record last verified: 2019-01

Locations

US (1)