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

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ClinicalTrials.gov Identifier: NCT02331498
Recruitment Status : Recruiting
First Posted : January 6, 2015
Last Update Posted : December 2, 2017
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Centre Antoine Lacassagne

Brief Summary:
A phase I/II study of pazopanib in combination with temozolomide in patients with newly diagnosed glioblastoma multiforme after surgery and RT-CT (PAZOGLIO study)

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Drug: Pazopanib Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 51 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Pazopanib in Combination With Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme After Surgery and RT-CT
Study Start Date : June 2015
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
A Pazopanib
Open label study with one group
Drug: Pazopanib
Study drug Pazopanib will be administered once tumoral evaluation has been performed and after Stupp Protocol (TMZ + Radiation) realisation.




Primary Outcome Measures :
  1. 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 ]
    To evaluate the Recommended Phase 2 Dose (RP2D) of pazopanib in oral route in addition to the maintenance phase of the Stupp protocol, regarding the toxicities that should not be more than 33 %


Secondary Outcome Measures :
  1. overall tolerance of pazopanib : number of biological toxicities, blood pressure and hemorragic events [ Time Frame: 2 years ]
    To define the overall tolerance of pazopanib associated with TMZ during the maintenance phase of the "Stupp protocol" regarding biological toxicities, blood pressure and hemorragic events

  2. antitumor activity of the adjunction of daily dose of pazopanib to the maintenance phase of the Stupp protocol [ Time Frame: 2 years ]
    To assess the antitumor activity of the adjunction of daily dose of pazopanib to the maintenance phase of the Stupp protocol according to the Revised Assessment in Neuro-Oncology (RANO) criteria (response rate) and the median duration of response.

  3. determine the median Progression-Free-Survival [ Time Frame: 12 months ]
    To determine the median Progression-Free-Survival (mPFS), the PFS rate at 12 (PFS-12) months.

  4. determine the median Overall Survival (mOS) [ Time Frame: 12 months ]
    To determine the median Overall Survival (mOS), the OS rate at 6 (OS-6) and 12 (OS-12) months.

  5. 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 ]
    To determine the pharmacokinetics (PK) profile of pazopanib when given in combination with TMZ.

  6. determine the pharmacokinetics (PK) profile of TMZ [ Time Frame: 2 years ]
    To determine the pharmacokinetics (PK) profile of TMZ when given in combination with pazopanib.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02331498


Contacts
Contact: Esma SAADA BOUZID, Md +33492031618 esma.saada-bouzid@nice.unicancer.fr
Contact: Christine LOVERA +33492031618 christine.lovera@nice.unicancer.fr

Locations
France
Centre Antoine Lacassagne Recruiting
Nice, Cedex 2, France, 06189
Contact: Esma SAADA BOUZID, Md    +33492031618    esma.saada-bouzid@nice.unicancer.fr   
Contact: Christine LOVERA    +33492031618    christine.lovera@nice.unicancer.fr   
Principal Investigator: Esma SAADA BOUZID, Dr         
Sub-Investigator: Jérôme BARRIERE, Pr.         
Sub-Investigator: Pierre Yves BONDIAU, Dr.         
Sponsors and Collaborators
Centre Antoine Lacassagne
GlaxoSmithKline
Investigators
Study Director: Christine LOVERA Centre Antoine Lacassagne

Additional Information:
Responsible Party: Centre Antoine Lacassagne
ClinicalTrials.gov Identifier: NCT02331498     History of Changes
Other Study ID Numbers: 2012/49
First Posted: January 6, 2015    Key Record Dates
Last Update Posted: December 2, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents