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

NCT ID: NCT01642017

Last Updated: 2018-08-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-22
• Study Completion Date: 2018-03-31

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)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pazopanib

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

Group Type: EXPERIMENTAL

Pazopanib

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Institut Claudius Regaud

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Loïc MOUREY, PhD

Role: PRINCIPAL_INVESTIGATOR

Institut Claudius Regaud

Locations

Hôpital Saint André

Bordeaux, , France

Centre François BACLESSE

Caen, , France

Centre Léon BERARD

Lyon, , France

Institut Claudius REGAUD

Toulouse, , France

Countries

France

Other Identifiers

11GENE06

Identifier Type: -

Identifier Source: org_study_id