NCT01408004

Brief Summary

In this study will be examined whether alternating treatment between two classes of drugs (TKI's and m-TOR inhibitors) postpones or prevents drug resistance in patients with renal cancer.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
101

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Nov 2011

Geographic Reach
1 country

17 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 7, 2011

Completed
4 months until next milestone

First Posted

Study publicly available on registry

August 2, 2011

Completed
3 months until next milestone

Study Start

First participant enrolled

November 1, 2011

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2014

Completed
Last Updated

July 16, 2014

Status Verified

July 1, 2014

Enrollment Period

2.4 years

First QC Date

April 7, 2011

Last Update Submit

July 15, 2014

Conditions

Clear Cell Renal Carcinoma

Keywords

Renal carcinomaResistanceReversibleTranslational

Outcome Measures

Primary Outcomes (1)

  • Progression free survival

    Randomization until earliest date of disease progression (according RECIST 1.1 criteria) or death, an expected average of one year

Secondary Outcomes (4)

  • Time to second progression

    Time between first and second progression, an expected average of five months

  • Change in Quality of life assessed by the FKSI-DRS and EORTC QLQ-C30 questionnaires compared to baseline

    From randomization until one month after ceasing study medication, an expected average of 18 months

  • Toxicity reported as number/percentage of patients with adverse events

    From randomization until one month after ceasing study medication, an expected average of 18 months

  • Overall survival

    Time between randomization and death, an estimated average of 2-5 years

Study Arms (2)

Alternating regimen

EXPERIMENTAL

In the experimental arm (Arm A) alternating treatment will consist of 8 weeks of Pazopanib 800 mg qd alternated by 8 weeks of Everolimus 10 mg qd until first progression(PD per RECIST 1.1)followed thereafter by Pazopanib (when PD after 8 weeks of Everolimus)or Everolimus (when PD after 8 weeks of Pazopanib) monotherapy until second progression.

Drug: PazopanibDrug: Everolimus

Sequential treatment

ACTIVE COMPARATOR

The comparative arm (Arm B) will be the standard regimen of Pazopanib (800 mg qd continuously) until progression, followed thereafter by Everolimus (10 mg qd continuously) until progression.

Drug: PazopanibDrug: Everolimus

Interventions

PazopanibDRUG

Tablet 800mg qd til progression

Also known as: Votrient, L01XE11
Sequential treatment
EverolimusDRUG

tablet 10 mg qd til progression

Also known as: Afinitor, L01XE10
Sequential treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), 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 ≥ 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 carcinoma.
  • Adequate organ system function.
  • Non-childbearing potential.

You may not qualify if:

  • 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.
  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product.
  • 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:
  • Cardiac angioplasty or stenting
  • Myocardial infarction
  • Stable or unstable angina pectoris.
  • 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).
  • Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥160 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg\].
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

St. Franciscus Gasthuis

Rotterdam, South Holland, Netherlands

Location

UMC Utrecht

Utrecht, Utrecht, 3508 GA, Netherlands

Location

Medisch Centrum Alkmaar

Alkmaar, Netherlands

Location

Acedemisch Medisch Centrum Amsterdam

Amsterdam, Netherlands

Location

NKI-AVL

Amsterdam, Netherlands

Location

Amphia ziekenhuis Breda

Breda, Netherlands

Location

Maxima Medisch Centrum

Eindhoven, Netherlands

Location

UMC Groningen

Groningen, Netherlands

Location

Atrium Medisch Centrum Heerlen

Heerlen, Netherlands

Location

Medische Centrum Leeuwarden

Leeuwarden, Netherlands

Location

Acedemisch ziekenhuis Maastricht

Maastricht, Netherlands

Location

St. Antonius ziekenhuis

Nieuwegein, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, Netherlands

Location

Orbis Medisch Centrum

Sittard-Geleen, Netherlands

Location

Haga Ziekenhuis

The Hague, Netherlands

Location

St. Elisabeth ziekenhuis

Tilburg, Netherlands

Location

Isala klinieken

Zwolle, Netherlands

Location

Related Publications (1)

  • Cirkel GA, Hamberg P, Sleijfer S, Loosveld OJL, Dercksen MW, Los M, Polee MB, van den Berkmortel F, Aarts MJ, Beerepoot LV, Groenewegen G, Lolkema MP, Tascilar M, Portielje JEA, Peters FPJ, Klumpen HJ, van der Noort V, Haanen JBAG, Voest EE; Dutch WIN-O Consortium. Alternating Treatment With Pazopanib and Everolimus vs Continuous Pazopanib to Delay Disease Progression in Patients With Metastatic Clear Cell Renal Cell Cancer: The ROPETAR Randomized Clinical Trial. JAMA Oncol. 2017 Apr 1;3(4):501-508. doi: 10.1001/jamaoncol.2016.5202.

    PMID: 27918762DERIVED

Related Links

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

pazopanibEverolimus

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic Chemicals

Study Officials

  • E.E. Voest, MD/PhD

    UMC Utrecht

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof. dr. E.E. Voest

Study Record Dates

First Submitted

April 7, 2011

First Posted

August 2, 2011

Study Start

November 1, 2011

Primary Completion

April 1, 2014

Study Completion

April 1, 2014

Last Updated

July 16, 2014

Record last verified: 2014-07

Locations

NL(17)