A randomized phase II study to explore the efficacy and feasibility of upfront bi-monthly rotations between Everolimus and Pazopanib with sequential treatment of first line Pazopanib and second line Everolimus until progression in patients with advanced or metastatic clear cell renal cancer.

Phase 2

Completed

• Conditions: Kidney cancer; Renal cancer; 10038364

• Registration Number: NL-OMON39600
• Lead Sponsor: Werkgroep Immunotherapie Nederland voor Oncologie

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• 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 cancer.;- Adequate organ system function.;- A female is eligible to enter and participate in this study if she is of: Non-childbearing potential (physiologically or by using adequate contraception) .

Exclusion Criteria

- Malignancy within the previous 5 years.;- 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 nonhealing 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.;- 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
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Progression-free survival: PFS is defined as time to progressive disease per<br /><br>RECIST 1.1 or death whichever comes first in arm A (alternating schedule) and<br /><br>after Pazopanib monotherapy in arm B. Comparing time to first PD with time to<br /><br>first PD.<br /><br>Patients who have not progressed or died at the date of the analysis cut-off or<br /><br>when they receive any further anticancer therapy will have their disease status<br /><br>censored at the time of the last adequate tumor assessment before the cut-off<br /><br>date or the anticancer therapy date. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Time to second progression or death: defined as time to progressive disease per<br /><br>RECIST 1.1 on Everolimus monotherapy (when PD after 8 weeks Pazopanib) or on<br /><br>Pazopanib monotherapy (when PD after 8 weeks Everolimus) as second line<br /><br>treatment in arm A and time to progressive disease on Everolimus in arm B.<br /><br>Comparing time to 2nd PD with time to 2nd PD.<br /><br>Quality of life and toxicity. Quality of life assessments and Common Toxicity<br /><br>Criteria will be used.<br /><br>Overall survival<br /><br>Pharmacodynamic measurements and pharmacokinetic assessments at the switch of<br /><br>Pazopanib and Everolimus and vice versa.<br /><br>Genetic analysis of tumorbioppsies (optional).</p><br>