Phase I/II Study of Pazopanib+ Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT02331498
• Date of registration: 10/11/2014
• Prospective Registration: Yes
• Primary sponsor: Centre Antoine Lacassagne
• Public title: Phase I/II Study of Pazopanib+ Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme PAZOGLIO
• Scientific title: A Phase I/II Study of Pazopanib in Combination With Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme After Surgery and RT-CT
• Date of first enrolment: June 2015
• Target sample size: 51
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02331498
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

France

Contacts

• Name: Christine LOVERA
• Affiliation: Centre Antoine Lacassagne

• Name: Esma SAADA BOUZID, Md

• Name: Esma SAADA BOUZID, Md

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subjects must provide written informed consent prior to performance of study-specific
procedures or assessments and must be willing to comply with treatment and follow up.

- Age = 18 years and < 70 years

- Histologically confirmed diagnosis of GBM

- Surgically treated other than exclusive biopsy (complete or partial resection) of the
GBM, for which adjuvant radiotherapy and chemotherapy is indicated

- Eligibility criteria that will need to be checked before patient registration and - No
TMZ interruption resulting in hematological toxicity should has occurred

- AND the delivery of radiation dose as defined in the Stupp protocol should be at least
equal to 80%

- Eastern Cooperative Oncology Group (ECOG) performance status of Glioblastoma = 2

- Life expectancy>3 months

- Measurable disease criteria : Based on the RANO criteria (Wen 2010) objective tumor
response will be assessed by MRI and 18F-DOPA PET)

- Archived tumor tissue must be available for all subjects for biomarker analysis before
and/or during treatment with investigational product.

- Stable doses of corticosteroid for more than 1 week.

- Adequate biological function

- Women of childbearing potential must have a negative serum pregnancy test within 14
days of first dose of study treatment and agree to use effective contraception, as
defined in Pregnancy Section in overall Safety Section during the study and for 6
months following the last dose of investigational product.

Exclusion Criteria:

- Prior malignancy.

- Surgical treatment consisting in exclusive biopsy or absence of initial surgery

- Pre-treated GBM

- Allergy to any of the tested drugs

- Clinically significant gastrointestinal abnormalities that may increase the risk for
gastrointestinal bleeding including,

- Clinically significant gastrointestinal abnormalities that may affect absorption of
investigational product

- Corrected QT interval (QTc) > 480 msecs

- History of any one or more of ardiovascular conditions within the past 6 months

- Poorly controlled hypertension

- History of cerebrovascular accident including transient ischemic attack (TIA),
pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

- Major surgery or trauma within 28 days prior to first dose of investigational product
and/or presence of any non-healing wound, fracture, or ulcer (procedures such as
catheter placement not considered to be major surgery).

- Evidence of active bleeding or bleeding diathesis.

- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that
increase the risk of pulmonary hemorrhage

- Recent hemoptysis

- Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
could interfere with subject's safety, provision of informed consent, or compliance to
study procedures.

- Unable or unwilling to discontinue use of prohibited medications listed in Appendix C
for at least 14 days or five half-lives of a drug (whichever is longer) prior to the
first dose of study drug and for the duration of the study (Appendix C).

- Treatment with any of the following anti-cancer therapies:

- radiation therapy, surgery or tumor embolization within 14 days prior to the
first dose of pazoapnib OR

- chemotherapy, immunotherapy, biologic therapy, investigational therapy or
hormonal therapy within 14 days or five half-lives of a drug (whichever is
longer) prior to the first dose of Pazopanib

- Administration of any non-oncologic investigational drug within 30 days or 5
half-lives whichever is longer prior to receiving the first dose of study treatment

- Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
progressing in severity, except alopecia.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Glioblastoma Multiforme

Intervention(s)

Drug: Pazopanib

Primary Outcome(s)

Recommended Phase 2 Dose (RP2D) of pazopanib in oral route in addition to the maintenance phase of the Stupp protocol, according the rate (33 %) of tolerate toxicities [Time Frame: phase I]

Secondary Outcome(s)

determine the pharmacokinetics (PK) profile of TMZ [Time Frame: 2 years]

overall tolerance of pazopanib : number of biological toxicities, blood pressure and hemorragic events [Time Frame: 2 years]

antitumor activity of the adjunction of daily dose of pazopanib to the maintenance phase of the Stupp protocol [Time Frame: 2 years]

determine the median Progression-Free-Survival [Time Frame: 12 months]

pharmacokinetics profile: area under curve regarding plasma concentration /time between 0 and 8 h (AUC0-8 hours) from 0 to 24 h (AUC 0-24 hours), maximum plasma concentration (Cmax), time to the concentration maximum (Tmax) and plasma half-life (t1/2) [Time Frame: 2 years]

determine the median Overall Survival (mOS) [Time Frame: 12 months]

Secondary ID(s)

2012/49

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline