Phase I Clinical and Pharmacokinetic Study of Pazopanib in a Population of Frail Elderly Patients According SIOG Criteria (VOTRAGE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Institut Claudius Regaud
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Institut Claudius Regaud
ClinicalTrials.gov Identifier:
NCT01642017
First received: July 13, 2012
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

This is an open-label, multicenter, non-randomized, phase 1 dose escalation clinical trial to determine the MTD (Maximal Tolerated Dose) of Pazopanib in a population of frail elderly patients, selected according to the International Society of Geriatric Oncology (SIOG)classification (Group 2).

It is expected that a total number of 30 patients maximum will be enrolled in the study on 30 months : 18 months accrual - 12 months follow up.

Eligible patients will be enrolled into a standard 3+3 design with a starting dose of Pazopanib administered orally at 400 mg per day, in 28-day cycles. Then, further dose levels will be explored.

Toxicity of the schedule will be assessed during the first cycle. Patients will receive study medication until disease progression. After treatment discontinuation, patients will be followed during one year.


Condition Intervention Phase
Metastatic Cancer (Different Solid Tumour Types)
Drug: Pazopanib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Clinical and Pharmacokinetic Study of Pazopanib in a Population of Frail Elderly Patients According SIOG Criteria

Resource links provided by NLM:


Further study details as provided by Institut Claudius Regaud:

Primary Outcome Measures:
  • Dose limiting toxicity (DLT) incidence (according DLT definition) during the first treatment cycle with pazopanib (28 days) [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    The MTD (Maximum Tolerated Dose) is defined as the highest dose level for which 6 patients were treated with a maximum of 1 patient presenting a DLT during the first cycle of treatment


Secondary Outcome Measures:
  • Safety and tolerability assessments using the descriptions and grading scales found in the CTCAE (Common Terminology Criteria for Adverse Events) version 4.0 NCI [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Measure of Pazopanib plasma concentration during treatment period (objective : assessment of pharmacokinetics of Pazopanib in this population) [ Time Frame: .8 time points (cycle 1 Day 1), 3 time points (cycle 1 D15) and 1 pre dose time point each day 1 of the following cycles (over a period of 4 years for measures in all patients) ] [ Designated as safety issue: No ]
    Plasma concentrations of pazopanib will be determined using a validated LC-MS-MS method -

  • Geriatric criteria measured by comprehensive geriatric assessment which evaluate medical, functional and psychosocial aspects of elderly patients [ Time Frame: 4 years ] [ Designated as safety issue: No ]

    The impact of treatment on the geriatric assessment will be done using :

    • G8 : screening test
    • ADL: Activities Daily Living
    • IADL: Instrumental Activities Daily Living
    • MMSE: Mini-mental State Examination
    • SPPB: Short Physical Performance Battery
    • MNA: Mini-nutritional Assessment
    • CAM: Confusion Assessment Method
    • GDS-15: Geriatric Depression Scale
    • CIRS-G: Cumulative Illness Rating Scale for Geriatrics,

  • Rate of objective response according to RECIST criteria [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Tumor assessment will be performed at screening visit, every 2 cycles and at the end of study visit and anytime if clinically indicated


Estimated Enrollment: 30
Study Start Date: September 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib
Pazopanib : 3 dose levels are defined : 400, 600 and 800 mg per day.
Drug: Pazopanib
Pazopanib will be administered orally at the starting dose of 400 mg/day in 28-days cycles ; barring limiting toxicities the dose of pazopanib will escalate in several steps (a maximum of 3 dose levels are defined : 400, 600 and 800 mg/day). The pazopanib will be administered at the same dosa until disease progression.

  Eligibility

Ages Eligible for Study:   75 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Age ≥ to 75 years old
  3. Patient with metastatic cancer among renal cell carcinoma, non small cell lung cancer, pancreatic neuroendocrine cancer, sarcoma , ovarian cancer , thyroid cancer, bladder cancer or breast cancers, who cannot receive any treatment with curative intent.
  4. WHO PS ≤ 2,
  5. Life expectancy ≥ 3 months,
  6. Group 2 (vulnerable) according to SIOG classification,
  7. Adequate organ system function as defined in provided Table

Exclusion Criteria:

  1. Patient with a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma with PSA <1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, and who is deemed at low risk for recurrence by his/her treating physician,
  2. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug.
  3. Criteria of group 3 according to SIOG classification,
  4. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

    •Active peptic ulcer disease

    •Known intraluminal metastatic lesion/s with risk of bleeding

    •Inflammatory bowel disease (e.g. ulcerative colitis, crohn's disease), or other gastrointestinal conditions with increased risk of perforation

    •History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.

  5. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

    •Malabsorption syndrome

    •Major resection of the stomach or small bowel.

  6. Presence of uncontrolled infection.
  7. Corrected QT interval (QTc) > 480 msecs using Bazett's formula
  8. Anti-coagulants treatment (preventive or curative)
  9. History of any one or more of the following cardiovascular conditions within the past 6 months:

    • Cardiac angioplasty or stenting

    • Myocardial infarction

    • Unstable angina

    • Coronary artery bypass graft surgery

    • Symptomatic peripheral vascular disease
    • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
  10. Poorly controlled hypertension
  11. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
  12. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer
  13. Evidence of active bleeding or bleeding diathesis.

14 Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

15. Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug.

16. 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.

17. Unable or unwilling to discontinue use of prohibited medications list in Appendix 7 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

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

  • radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib 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

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

    20. Patient not affiliated with social system in France.

    21. Patient deprived of liberty or under guardianship

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01642017

Contacts
Contact: Loïc MOUREY, PhD + 33 5 61 42 45 48 mourey.loic@claudiusregaud.fr

Locations
France
Hôpital Saint André Recruiting
Bordeaux, France, 33075
Contact: Alain RAVAUD, PhD    + 33 5 56 79 56 79    alain.ravaud@chu-bordeaux.fr   
Principal Investigator: Alain RAVAUD, PhD         
Sub-Investigator: Laurence DIGUE, PhD         
Sub-Investigator: Marine GROSS-GOUPIL, PhD         
Sub-Investigator: Denis SMITH, PhD         
Sub-Investigator: Nathalie TRUFFLANDIER, PhD         
Centre François BACLESSE Recruiting
Caen, France, 14076
Contact: Emmanuel SEVIN, PhD    + 33 2 31 45 50 02    e.sevin@baclesse.fr   
Principal Investigator: Emmanuel SEVIN, PhD         
Sub-Investigator: Katharina GUNZER, PhD         
Sub-Investigator: Florence JOLY, PhD         
Sub-Investigator: Laura MOISE, PhD         
Centre Léon BERARD Recruiting
Lyon, France, 69008
Contact: Catherine TERRET, PhD    + 33 4 78 78 27 72    catherine.terret@lyon.unicancer.fr   
Principal Investigator: Catherine TERRET, PhD         
Sub-Investigator: Jean-Yves BLAY, PhD         
Sub-Investigator: Philippe CASSIER, PhD         
Institut Claudius REGAUD Recruiting
Toulouse, France, 31052
Contact: Loïc MOUREY, PhD    +33 5.61.42.45.48    mourey.loic@claudiusregaud.fr   
Principal Investigator: Loïc MOUREY, PhD         
Sub-Investigator: Jean-pierre DELORD, PhD         
Sponsors and Collaborators
Institut Claudius Regaud
GlaxoSmithKline
Investigators
Principal Investigator: Loïc MOUREY, PhD Institut Claudius Regaud
  More Information

No publications provided

Responsible Party: Institut Claudius Regaud
ClinicalTrials.gov Identifier: NCT01642017     History of Changes
Other Study ID Numbers: 11GENE06
Study First Received: July 13, 2012
Last Updated: June 3, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Institut Claudius Regaud:
Phase I, Pazopanib, Frail elderly patients, Pharmacokinetics

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on August 21, 2014