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Melanotan-I

Afamelanotide, MT-I, [Nle4-D-Phe7]-α-MSH, Scenesse, CUV-1647

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Studies 225
Trials 100
Completed PHASE2 INTERVENTIONAL NCT00433381

Bevacizumab and Irinotecan or Temozolomide in Treating Patients With Recurrent or Refractory Glioblastoma Multiforme or Gliosarcoma

View on ClinicalTrials.gov Updated Dec 15, 2025

Brief Summary

This randomized phase II trial is studying the side effects and how well giving bevacizumab together with irinotecan or temozolomide works in treating patients with recurrent or refractory glioblastoma multiforme or gliosarcoma. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with irinotecan or temozolomide may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES: I. Determine the efficacy of bevacizumab and irinotecan hydrochloride, in terms of 6-month progression-free survival rate, in patients with recurrent or refractory intracranial glioblastoma multiforme or gliosarcoma. II. Determine the adverse event profile and tolerability of bevacizumab and temozolomide in these patients. SECONDARY OBJECTIVES: I. Determine the efficacy of bevacizumab and temozolomide, in terms of 6-month progression-free survival rate, in patients previously treated with temozolomide. II. Determine the efficacy of bevacizumab and irinotecan hydrochloride, in terms of objective response, in patients with measurable disease. III. Determine the efficacy of bevacizumab and temozolomide, in terms of objective response, in patients with measurable disease who were previously treated with temozolomide. IV. Determine the toxicity profile and tolerability of bevacizumab and irinotecan hydrochloride in these patients. TERTIARY OBJECTIVES: I. Assess the potential role of perfusion MRI and magnetic resonance spectroscopy imaging as an early indicator of response to therapy after 2 weeks of treatment with bevacizumab. II. Assess the potential role of perfusion MRI and magnetic resonance spectroscopy imaging as a prognostic indicator based on images taken at baseline, at 2 weeks, and after 2 courses of study treatment. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (\< 50 vs \>= 50 years of age) and Karnofsky performance status (70-80% vs 90-100%). Patients are randomized to 1 of 2 treatment arms with a 2:1 ratio (arm I:arm II). ARM I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral temozolomide once daily on days 1-21. ARM II: Patients receive bevacizumab IV as in Arm I followed by irinotecan hydrochloride IV over 90 minutes on days 1 and 15. In both arms, treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. All patients undergo MRI at baseline and at every 2 courses (no 2-week MRI) per standard of care until progression or discontinuation of treatment to assess areas of breakdown of the blood-brain barrier. Patients undergo an additional MRI after study therapy. Consenting patients also undergo diffusion and perfusion MRI and magnetic resonance spectroscopic imaging for correlative studies. After completion of study therapy, patients are followed up for at least 1 month.

Interventions

Name: Bevacizumab
Type: BIOLOGICAL
Description: Given IV
Name: Irinotecan Hydrochloride
Type: DRUG
Description: Given IV
Name: Temozolomide
Type: DRUG
Description: Given orally

Primary Outcomes

Measure: Count/Percentage of Patients Progression-free at 6 Months for Bevacizumab and Irinotecan Hydrochloride Arm
TimeFrame: From randomization to six months.
Description: Progression defined as ≥ 25% increase in the size of enhancing tumor or any new tumor; or neurologically worse, and steroids stable or increased. Percentage is calculated by taking the number of patients who have survived 6 months without progression of study disease after study registration in the numerator. The denominator consists of all patients except those who were found retrospectively to be ineligible or who were lost to follow-up after less than 6 months.
Measure: Count/Percentage of Patients Discontinuing Treatment Due to Treatment-related Medical Complications(Bevacizumab and Temozolomide Arm)
TimeFrame: From randomization to end of treatment (treatment can continue up to 24 months for patients with stable or responding tumor).
Description: This endpoint determines tolerability of this treatment arm. If tolerable, then the secondary endpoint of treatment efficacy for this arm occurs. Percentage is calculated by taking the number of patients who did not stop bevacizumab and temozolomide treatment due to medical complications in the numerator. The denominator consists of all patients except those who were found retrospectively to be ineligible or who did not begin treatment.
Measure: Number of Participants With Predicted Progression-free Survival at 6 Months (PFS-6)
TimeFrame: 2 and 8 weeks posttreatment, and every 2 months until 96wks
Description: Magnetic Resonance Imaging with Spectroscopy (MRS or MRSI) metabolic tumor ratios will be used to predict 6-month progression-free survival (PFS-6) over all study participants. Ratios of NAA/Cho, Cho/Cr, NAA/Cr measured at 2 weeks and 8 weeks and every 2 months until 96wks were used to predict survival, and time to progression, evaluated at 96wks, is the determinate of PFS at 6months (PFS-6). Subjects will not be analyzed by arm.
Measure: Number of Participants With Predicted Overall Survival (OS) at 12 Months
TimeFrame: 2 and 8 weeks posttreatment, and every 2 months until 96wks
Description: Magnetic Resonance Imaging with Spectroscopy (MRS or MRSI) metabolic tumor ratios will be used to predict 12-month overall survival (OS). Ratios of NAA/Cho, Cho/Cr, NAA/Cr measured at 2 weeks and 8 weeks and every 2 months until 96wks were used to predict survival, and time to death, evaluated at 96wks, is the determinate of OS at 12 months. Subjects will not be analyzed by arm.

Trial Information

NCT ID

NCT00433381

Status

Completed

Study Type

INTERVENTIONAL

Phases

PHASE2

Sponsor

National Cancer Institute (NCI)

Last Updated

December 15, 2025

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