RO4929097 in Treating Patients With Recurrent Invasive Gliomas

NCT01269411 | Terminated Phase 1

• 4 other identifiers: NCI-2011-02565PHL-075N01CM00032CDR0000691784
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of RO4929097 in treating patients with recurrent invasive gliomas. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Conditions

Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor

Outcome Measures

Primary Outcomes (2)

• Maximum-tolerated dose (MTD) defined as the dose level in which less than or equal to 1 out of 6 patients experience dose limiting toxicity (DLT) assessed using NCI CTCAE version 4.0

  21 days

• Pharmacokinetic (PK) profile of RO4909297

  Pre-dose, 1, 2, 4, 8, and 24 hours

Secondary Outcomes (4)

• Progression-free survival following treatment with R04929097

  From registration to time of progression or death, whichever occurs first, assessed up to 12 months

• Inhibition of p75NTR cleavage and processing

  Up to 12 months

• Establishment and growth of BTIC cultures in neurosphere growth conditions, effects on proliferation, ability to self-renewal, and ability to differentiate along lineage-specific pathways

  Up to 12 months

• Inhibition of Notch signaling, by assessing downstream target activation

  Up to 12 months

Study Arms (1)

Treatment (RO4929097 and surgery)

EXPERIMENTAL

PART A: Patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. PART B: Patients receive oral RO4929097 once daily on days 1-7 and undergo surgery on day 8. Beginning 28 days later, patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Procedure: therapeutic conventional surgery; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

gamma-secretase/Notch signalling pathway inhibitor RO4929097 DRUG

Given orally

Also known as: R4733, RO4929097

Treatment (RO4929097 and surgery)

therapeutic conventional surgery PROCEDURE

Undergo surgery

Treatment (RO4929097 and surgery)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (RO4929097 and surgery)

laboratory biomarker analysis OTHER

Correlative

Treatment (RO4929097 and surgery)

Eligibility Criteria

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

You may qualify if:

• Patients must have radiographic progression of a histologically confirmed glioblastoma, high-grade astrocytoma, NOS, anaplastic mixed oligo-astrocytoma, or anaplastic oligodendroglioma
• In patients that present radiographic evidence of progression after concurrent treatment with radiation and low-dose temozolomide, diagnosis of progression should be made after at least 2 cycles of monthly temozolomide in order to rule out pseudoprogression
• Secondary MGs (evolving from a prior low-grade glioma) can be included as long as they are considered malignant in the latest resection
• Patients must have at least one enhancing lesion that can be accurately measured as \> 1 X 1 cm on a MRI
• Prior treatment must include radiotherapy (with or without temozolomide)
• No limit to the number of prior recurrences or surgeries
• For Part B only, surgical resection should be considered a reasonable therapeutic option for a patient that can tolerate surgical resection
• Patients with multifocal disease can be included as long as resection is considered a reasonable option to manage the nodule that is progressing
• There must be sufficient tissue available (minimum from a 1 X 1 cm lesion) for a biopsy to be taken during surgery
• There must be sufficient tissue available for evaluation of p75\^NTR status from a prior surgery (using immunohistochemistry on fixed tissue or, in uncommon cases in which frozen tissue is available from a prior surgery, western blot) (part B)
• ECOG performance status \< 2 (Karnofsky \> 50%)
• Life expectancy of greater than 4 weeks
• Absolute neutrophil count \> 1,500/mcL
• Platelets \> 100,000/mcL
• Hemoglobin \> 90 g/L (or \> 9 g/dL)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Oligodendroglioma; Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide

Condition Hierarchy (Ancestors)

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

Study Officials

• Peter Forsyth

  University Health Network-Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 31, 2010
• First Posted: January 4, 2011
• Study Start: July 1, 2011
• Primary Completion: February 1, 2012
• Last Updated: February 7, 2013

Record last verified: 2013-02

Locations

CA (1)