A study to investigate if alternating Pazopanib and Everolimus avoids or postpones resistance

Phase 1

• Conditions: Advanced or metastatic clear cell renal cancer.; MedDRA version: 16.1Level: LLTClassification code 10038416Term: Renal clear cell carcinomaSystem Organ Class: 100000004864; MedDRA version: 16.1Level: LLTClassification code 10009251Term: Clear cell carcinoma of the kidneySystem Organ Class: 100000004864; MedDRA version: 16.1Level: LLTClassification code 10023400Term: Kidney cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-000127-32-NL
• Lead Sponsor: Werkgroep Immunotherapie Nederland voor Oncologie

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-01-28
• Last Update Posted: 18 March 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

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.

- Histologically confirmed diagnosis of progressive metastatic clear cell renal cell cancer defined as >10% of the tumor cells having the clear cell phenotype.

- Locally advanced (defined as disease not amenable to curative surgery or
radiation therapy) or metastatic RCC (equivalent to Stage IV RCC according to
AJCC staging

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

- Measurable disease.

- No prior systemic anti-cancer treatment against clear cell renal cell cancer.

- Adequate organ system function.

- Non-childbearing potential.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

- Prior malignancy.

- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.

- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
1)Active peptic ulcer disease.
2)Known intraluminal metastatic lesions with risk of bleeding.
3) Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation.
4)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:
1)Malabsorption syndrome.
2)Major resection of the stomach or small bowel.

-Presence of uncontrolled infection.

-Known past or present infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human Immunodeficiency Virus (HIV).

-Corrected QT interval (QTc) > 480 msecs using Bazett’s formula.

-History of one or more of the following cardiovascular conditions within the past 6 months:
1)Cardiac angioplasty or stenting
2)Myocardial infarction
3)Stable or unstable angina pectoris.
4)Coronary artery bypass graft surgery.
5)Symptomatic peripheral vascular disease
6)Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).

- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =160 mmHg or diastolic blood pressure (DBP) of = 90mmHg].

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

- 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 (procedures such as catheter placement not considered to be major).

- Evidence of active bleeding or bleeding diathesis.

- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.

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

- 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 or modify the dosing of interacting drugs as listed in Section 6.8.1. and 6.8.2 of the protocol 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.

- Pregnant or lactating female.

- 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified