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Clear Cell Renal CarcinomaPhase 2ROPETARNCT01408004

Rotating Pazopanib and Everolimus to Avoid Resistance

A Phase 2 study testing Pazopanib and Everolimus in people with Clear Cell Renal Carcinoma, run by Netherlands Working Group on Immunotherapy of Oncology at 17 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Clear Cell Renal Carcinoma
What is being tested?
Pazopanib and Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
101 participants
Where
17 sitesNetherlands
Study dates
Nov 2011to Apr 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • No prior systemic anti-cancer treatment against clear cell renal carcinoma.
  • Adequate organ system function.
  • Non-childbearing potential.

Who cannot join

  • 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).
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  • 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].
  • 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 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.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

Netherlands17 sites

  • Medisch Centrum Alkmaar

    Alkmaar

  • Acedemisch Medisch Centrum Amsterdam

    Amsterdam

  • NKI-AVL

    Amsterdam

  • Amphia ziekenhuis Breda

    Breda

  • Maxima Medisch Centrum

    Eindhoven

  • UMC Groningen

    Groningen

  • Atrium Medisch Centrum Heerlen

    Heerlen

  • Medische Centrum Leeuwarden

    Leeuwarden

  • Acedemisch ziekenhuis Maastricht

    Maastricht

  • St. Antonius ziekenhuis

    Nieuwegein

  • St. Franciscus Gasthuis

    Rotterdam, South Holland

  • Erasmus Medisch Centrum

    Rotterdam

  • Orbis Medisch Centrum

    Sittard-Geleen

  • Haga Ziekenhuis

    The Hague

  • St. Elisabeth ziekenhuis

    Tilburg

  • UMC Utrecht

    Utrecht, Utrecht, 3508 GA

  • Isala klinieken

    Zwolle

Other trials in Netherlands

About this study

Official title: A Randomized Phase II Study to Explore the Efficacy and Feasibility of Upfront Bi-monthly Rotations Between Everolimus and Pazopanib in Patients With Advanced or Metastatic Clear Cell Renal Cancer

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.

Read the detailed description

Current practice is to treat with VEGFR-TKI or mTOR inhibitors until progression and then continue with the next active agent. From a biological perspective, TKI's will most likely activate compensatory pathways which, may ultimately lead to the development of resistance. Recent studies suggest that resistance to treatment with TKI may be reversible after stopping treatment. There is therefore a rationale to alternate treatment to prevent or delay the occurrence of resistance.

Our hypothesis is that alternating active agents in clear cell renal carcinoma (ccRCC) may reduce side effects, improve tolerability and compliance of treatment and prolong progression free survival and overall survival compared to the standard of care.

Being tested
Pazopanib, Everolimus
Keywords
Renal carcinoma, Resistance, Reversible, Translational
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PazopanibDrug

    Also called Votrient, L01XE11

    Tablet 800mg qd til progression

  • EverolimusDrug

    Also called Afinitor, L01XE10

    tablet 10 mg qd til progression

  • PazopanibDrug

    Also called Votrient, L01XE11

    tablet 800mg qd, alternating schedule: 8 weeks Pazopanib, 8 weeks Everolimus

  • EverolimusDrug

    Also called Afinitor, L01XE10

    tablet 10mg qd, alternating schedule: 8 weeks Pazopanib, 8 weeks Everolimus

  • EverolimusDrug

    Also called Afinitor, L01XE10

    Everolimus 10mg qd monotherapy until second progression (PD per RECIST 1.1)when first progression after 8 weeks of Pazopanib in alternating regimen

  • PazopanibDrug

    Also called Votrient, L01XE11

    Pazopanib 800mg qd monotherapy until second progression (PD per RECIST 1.1) when first progression after 8 weeks of Everolimus in alternating regimen

Study groups in NCT01408004
Study groupRoleWhat they receive
Alternating regimenExperimentalIn 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.
Receives: Drug: Pazopanib; Drug: Everolimus
Sequential treatmentActive comparatorThe 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.
Receives: Drug: Pazopanib; Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival

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

Secondary outcomes (4)

  1. Time to second progression

    Time between first progression and second progression (PD) per RECIST 1.1 on Everolimus monotherapy (when PD after 8 weeks Pazopanib) or Pazopanib monotherapy (when PD after 8 weeks Everolimus) as second line treatment in experimental arm and time to progressive disease on Everolimus as second line treatment in comparative arm.

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

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

    Quality of life will be assessed bi-monthly by using the FACT Kidney Symptom Index (FKSI)-Disease Related Symptom (DRS)and the EORTC QLQ-C30 questionnaire. The symptoms covered by the FKSI-DRS include fatigue, pain, weight loss, dyspnea, cough, fever and hematuria. The EORTC QLQ-C30 questionnaire evaluates five functional scales (physical, role, emotional, social and cognitive functioning), three symptom scales (fatigue, pain, nausea, and vomiting), a global health status/QoL scale, and six single items (dyspnea, diarrhea, constipation, anorexia, insomnia and financial impact).

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

  3. Toxicity reported as number/percentage of patients with adverse events

    Adverse events will be reported according Criteria for Adverse Events v4.0 (NCI CTCAE v4)

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

  4. Overall survival

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2011 (estimated)
  2. Study startNov 2011
  3. Primary completionApr 2014
  4. Study completionApr 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01408004
Sponsor's protocol ID
NL35303.041.11
Acronym
ROPETAR
Status last verified
Jul 2014
First submitted
7 Apr 2011
Last updated
16 Jul 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 27918762

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pazopanib and Everolimus in people with Clear Cell Renal Carcinoma, run by Netherlands Working Group on Immunotherapy of Oncology at 17 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (time frame: Randomization until earliest date of disease progression (according RECIST 1.1 criteria) or death, an expected average of one year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01408004, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2014.

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