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

NCT01642017 | Terminated Phase 1

• 1 other identifier: 11GENE06
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Metastatic Cancer (Different Solid Tumour Types)

Keywords

Phase I, Pazopanib, Frail elderly patients, Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT) incidence (according DLT definition) during the first treatment cycle with pazopanib (28 days)

  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

  7.5 years

Secondary Outcomes (4)

• Safety and tolerability assessments using the descriptions and grading scales found in the CTCAE (Common Terminology Criteria for Adverse Events) version 4.0 NCI

  7.5 years

• Measure of Pazopanib plasma concentration during treatment period (objective : assessment of pharmacokinetics of Pazopanib in this population)

  .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 7.5 years for measures in all patients)

• Geriatric criteria measured by comprehensive geriatric assessment which evaluate medical, functional and psychosocial aspects of elderly patients

  7.5 years

• Rate of objective response according to RECIST criteria

  7.5 years

Study Arms (1)

Pazopanib

EXPERIMENTAL

Pazopanib : 3 dose levels are defined : 400, 600 and 800 mg per day.

Drug: Pazopanib

Interventions

Pazopanib DRUG

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.

Pazopanib

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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 ≥ to 75 years old
• 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.
• WHO PS ≤ 2,
• Life expectancy ≥ 3 months,
• Group 2 (vulnerable) according to SIOG classification,
• Adequate organ system function as defined in provided Table

You may not qualify if:

• 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,
• 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.
• Criteria of group 3 according to SIOG classification,
• 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.
• 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.
• Presence of uncontrolled infection.
• Corrected QT interval (QTc) \> 480 msecs using Bazett's formula
• Anti-coagulants treatment (preventive or curative)
• History of any one or more of the following cardiovascular conditions within the past 6 months:

Sponsors & Collaborators

• Institut Claudius Regaud: lead
• Novartis: collaborator

Study Sites (4)

Hôpital Saint André

Bordeaux, 33075, France

Location

Centre François BACLESSE

Caen, 14076, France

Location

Centre Léon BERARD

Lyon, 69008, France

Location

Institut Claudius REGAUD

Toulouse, 31052, France

Location

Related Publications (1)

• Mourey L, Le Louedec F, Ravaud A, Paludetto MN, Digue L, Gomez-Roca CA, Valentin T, Balardy L, Olivier P, Cabarrou B, Filleron T, Chatelut E. VOTRAGE study: Phase I dose-escalation study of pazopanib in unfit older patients. J Geriatr Oncol. 2021 Jun;12(5):759-764. doi: 10.1016/j.jgo.2021.02.006. Epub 2021 Mar 11.

  PMID: 33715996 RESULT

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Loïc MOUREY, PhD

  Institut Claudius Regaud

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2012
• First Posted: July 17, 2012
• Study Start: November 22, 2012
• Primary Completion: September 1, 2017
• Study Completion: March 1, 2018
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

FR (4)