Safety and Imaging Study of GC1008 in Glioma

NCT01472731 | Completed Phase 2 DMC

• 2 other identifiers: GC10082010-021639-15
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Brain tumors account for only 2% of all cancers but result in a disproportionate share of cancer morbidity and mortality. The five-year survival rates for the most common histologic subtypes, anaplastic astrocytoma and glioblastoma (glioblastoma multiforme, GBM), are 30% and 10%, respectively. Drugs affecting transforming growth factor-β (TGF-β) might be of great interest for malignant glioma treatment. TGF-β is an oncogenic factor in advanced tumors where it induces proliferation, angiogenesis, invasion, and metastasis as well as suppresses the antitumoral immune response. In addition TGF-β and its TGF-β receptors, TβRI and TβRII, are overexpressed in GBMs. TGF-β signaling is involved in multiple steps of GBM development. GC1008 is an antibody that is capable of neutralizing TGF-β and may therefore offer a new treatment option for patients with malignant glioma. For therapeutic success, it may be essential for GC1008 to reach the target site, in this case located in the brain. We will be able to prove this with 89Zr-GC1008 PET imaging. This imaging method also allows quantification of the amount of GC1008 reaching the tumor. This study consists of 2 parts. In part 1, patients with a suspicion of a malignant glioma undergo an 89Zr-GC1008 PET scan before standard (surgical)treatment. In part 2, patients with relapsed malignant glioma will undergo an 89Zr-GC1008 PET scan and will be treated with GC1008 in a phase II study as there is no standard treatment for these patients. We hypothesize that GC1008 uptake in brain tumors can be visualized and quantified using the 89Zr-GC1008 PET scan and GC1008 might offer a new treatment option for patients with relapsed malignant gliomas.

Conditions

Primary Brain Tumors

Keywords

GC1008; PET imaging; primary brain tumors; recurrent high grade glioma's

Outcome Measures

Primary Outcomes (2)

• Biomarker imaging

  Part 1, Biomarker imaging: 89Zr-GC1008 PET imaging in patients with suspicion of a malignant glioma: Primary endpoint: \- Quantification of uptake of 89Zr-GC1008 as determined by PET imaging. The data obtained from the PET-scans will be quantified as standardized uptake value (SUV).

  2 years

• Quantification of uptake

  Part 2, In relapsed malignant glioma patients 89Zr-GC1008 PET imaging followed by participation in phase 2 study of GC1008 Primary endpoint: \- Quantification of uptake of 89Zr-GC1008 in relapsed malignant glioma patients as determined by PET imaging. The data obtained from the PET-scans will be quantified as standardized uptake value (SUV).

  2 years

Secondary Outcomes (3)

• Correlation of 89Zr-GC1008 tumor uptake

  2 years

• Correlation of 89Zr-GC1008 tumor uptake

  2 years

• Secondary endpoints Part 2

  2 years

Study Arms (1)

GC1008 imaging and treatment

EXPERIMENTAL

Part 1: Feasibility of 89Zr-GC1008 PET imaging in patients with suspicion of a malignant glioma to assess if GC1008 penetrates into the brain tumor and to quantify its uptake. Part 2: 89Zr-GC1008 PET imaging in patients with relapsed malignant glioma and phase II extension study with therapeutic GC1008 in these patients

Other: 89Zr-GC1008; Drug: GC1008

Interventions

89Zr-GC1008 OTHER

radioactive labeled GC1008, intravenous use, 37 MBq total

Also known as: 89Zr-fresolimumab

GC1008 imaging and treatment

GC1008 DRUG

5 mg/kg intravenous use

Also known as: fresolimumab

GC1008 imaging and treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 18 years
• WHO 0,1,2
• Suspicion of malignant glioma on contrast-enhanced MRI
• Able to give written informed consent

You may not qualify if:

• Meningeal carcinomatosis, uncontrolled seizures, or a disease that either causes or threatens neurologic compromise
• Pregnant or nursing women
• Known allergy to component of 89Zr-GC1008
• Significant medical or psychosocial problems
• Part 2
• Relapsed malignant glioma
• Patient may have undergone surgery for the recurrence. Residual and measurable disease after surgery is not required. Surgery must have confirmed the recurrence. Post-operative MRI must be made within 48 hours following surgery
• For non operated patients, recurrent disease must be at least one bidimensionally measurable target lesion (contrast enhancing lesion) with one diameter of at least 2cm, based on MRI scan done within 4 weeks prior to start of treatment
• years
• WHO 0,1,2
• Serum albumin ≥3.0 g/dL
• Adequate organ function including:
• Hb ≥10.0 g/dL
• ANC ≥1,500/mm3
• platelets ≥100,000/mm3

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

fresolimumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Annemiek ME Walenkamp, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2011
• First Posted: November 16, 2011
• Study Start: December 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: May 6, 2024

Record last verified: 2024-05

Locations

NL (1)