A Phase II/III Study of High-dose, Intermittent Sunitinib in Patients With Recurrent Glioblastoma Multiforme

NCT03025893 | Unknown Phase 2 DMC

• 1 other identifier: 2016.221
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

In this study the investigators will evaluate the effect of high-dose, intermittent sunitinib versus treatment with lomustine in patients with recurrent glioblastoma multiforme. The investigators hypothesize that sunitinib, when given in a high-dose, intermittent schedule, will achieve adequate concentration levels in the tumor and will, besides its anti-angiogenic properties, inhibit gliomagenesis by inhibition of multiple kinases.

Conditions

Glioblastoma Multiforme; Glioblastoma, Adult; Glioblastoma; Recurrent Brain Tumor; GBM

Keywords

Sunitinib; Lomustine; High-dose; Intermittent

Outcome Measures

Primary Outcomes (1)

• Six-month progression-free survival (PFS-6)

  From the date of randomization up to the date of first progression or death (any cause) whichever comes first, assessed up to 36 months (End of Study).

Secondary Outcomes (6)

• Overall survival (OS)

  From the date of randomization up to the date of death, assessed up to 36 months. If study medication is discontinued for any reason, survival follow-up takes place every 12 weeks, also assessed up to 36 months (End of Study).

• Objective radiological response rate

  Disease will be assessed by MRI every 6 weeks for the first 6 months and every 12 weeks until documented progression, assessed up to 36 months (End of Study).

• Adverse events (AEs)

  AEs will be monitored at every visit during study treatment or after discontinuation of study treatment in the case adverse events have not subsided, assessed up to 36 months (End of Study).

• Health-related quality of life (HRQoL)

  HRQoL assessments will be performed at baseline and every 6 weeks until documented progression, assessed up to 36 months (End of Study).

• Blood markers (TEP: tumor educated platelets, and miRNA)

  Blood samples for RNA profiling will be drawn simultaneously with regular blood samples on five specific time points during study treatment and will be assessed after 36 months (End of Study).

Study Arms (2)

Sunitinib

EXPERIMENTAL

Patients in this experimental arm will receive sunitinib in a high-dose, intermittent schedule.

Drug: Sunitinib

Lomustine

ACTIVE COMPARATOR

Patients in this control arm will receive lomustine, currently used as second-line treatment in the case of recurrence.

Drug: Lomustine

Interventions

Sunitinib DRUG

Sunitinib, 300 mg administered orally in a weekly schedule.

Also known as: Sutent

Sunitinib

Lomustine DRUG

Lomustine 110 mg/m2, taken orally on day 1 every 6 weeks.

Also known as: CCNU

Lomustine

Eligibility Criteria

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

You may qualify if:

• Signed (by the patient or legally acceptable representative) and dated Informed Consent Form
• Histologically confirmed de novo or secondary glioblastoma with unequivocal first progression, at least 3 months off radiotherapy.
• No more than one line of chemotherapy (concurrent and adjuvant temozolomide based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization.
• Patients may have undergone surgery for recurrence. If operated, residual and measurable disease after surgery is not required but surgery must have confirmed the recurrence.
• No radiotherapy, stereotactic radiosurgery or brachytherapy as treatment for recurrence.
• Patients must have a Karnofsky Performance Score ≥ 70%
• Patients need to have adequate hematological, renal and hepatic function as assessed by the following laboratory requirements to be conducted within seven days prior to start study treatment:
• Hemoglobin ≥ 7.0 mmol/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• ALAT and ASAT ≤ 2.5 x ULN
• Serum creatinine eGFR ≥ 50 ml/min
• Albumin ≥ 25 g/L
• Age ≥ 18 years

You may not qualify if:

• Evidence of a significant uncontrolled concomitant disease, such as cardiovascular disease (including stroke, New York Heart Association Class III or IV cardiac disease or myocardial infarction within 6 months prior to screening, unstable arrhythmia, clinically significant valvular heart disease and unstable angina); nervous system, pulmonary (including obstructive pulmonary disease and history of symptomatic bronchospasm), renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture.
• Patients with a prior (\< 5 years) or concomitant second malignancy.
• Prior radiotherapy in the abdomen or in the lungs or in more than 3 vertebrae in the spine (Less than 3 vertebrae are considered a small radiation field and eligibility will be decided on an individual basis from the PI).
• Poorly controlled hypertension despite adequate blood pressure medication. Blood pressure must be ≤ 160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements.
• Known active bacterial, viral, fungal, mycobacterial, or other infection (including HIV and atypical mycobacterial disease, but excluding fungal infection of the nail beds.)
• Initial MR-scan of the brain showing intratumoral hemorrhage, except for stable post-operative grade 1 hemorrhage.
• Known hypersensitivity to sunitinib or to its excipients.
• Presence of any significant central nervous system or psychiatric disorder(s) that would interfere with the patient's compliance.
• Use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes.
• Use of strong hepatic enzyme-inducing antiepileptic drugs, such as carbamazepine, phenobarbital and phenytoin. If a patient uses one or more of these specific antiepileptic drugs, they must switch to an antiepileptic drug that does not interact with cytochrome P450 (CYP450) liver enzymes, such as levetiracetam, prior to the start of study treatment.
• Drug or alcohol abuse.
• Females who are pregnant or breast-feeding.
• Any evidence of a disease or condition that might affect compliance with the protocol or interpretation of the study results or render the patient at high risk from treatment complications.
• Unwillingness or inability to comply with study and follow-up procedures.
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (3)

VU University Medical Center

Amsterdam, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Radboud UMC

Nijmegen, Netherlands

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Sunitinib; Lomustine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; 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)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Study Officials

• Myra E Van Linde, MD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Myra E Van Linde, MD

CONTACT

+31 20 444 4321; trialoffice-onc@vumc.nl

Jorien Janssen, MD

CONTACT

jorien.janssen@radboudumc.nl; trialoffice-onc@vumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist Department of Medical Oncology

Study Record Dates

• First Submitted: January 9, 2017
• First Posted: January 20, 2017
• Study Start: August 31, 2018
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: April 19, 2021

Record last verified: 2021-04

Locations

NL (3)