Third Line TKI After 2 TKIs in Patients With mRCC (Tokio Study) (TOKIO)

March 5, 2018 updated by: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Activity and Safety of Third Line Tyrosin Kinase Inhibitor (TKI) After 2 Tyrosin Kinase Inhibitors (TKIs) in Patients With Metastatic Renal Cell Carcinoma (mRCC) (Tokio Study)

The study aims to evaluate the efficacy of a third TKI after two previous lines of therapy with TKIs, in terms of median progression free survival (mPFS), in patients affected by metastatic renal cancer cell.

Patients receiving the sequence Sunitinib- Axitinib, will receive Sorafenib.

Patients receiving the sequence Pazopanib-Sorafenib, will receive Sunitinib.

Sorafenib dosage 400mg orally, twice a day.

Sunitinib dosage 50 mg 4 weeks on followed by 2 weeks a rest.

The therapy will be continued until disease progression or unacceptable toxicity.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Advanced RCC presents poor prognosis, because his pathogenesis is not clearly understood.

Additionally, the Von Hippel Lindau (VHL) gene is mutated in the majority of sporadic and familial clear cell renal cancer. The mechanism by which VHL mutation leads to RCC development and progression is postulate to be in part thought production of the protein VEGF (Vascular Endothelial Grow Factor).

VEGF over-expression may be pertinent in RCC via multiple mechanism in addition to angiogenesis, including effects on dendritic cells and inhibition of apoptosis through preservation of cyclin dependent kinase inhibitors.

VEGF expression could represented an independent prognostic factors for survival possibly linking expression of this protein with clinical outcome.

Sunitinib and pazopanib are the standard therapy as first line in mRCC. At sunitinib failure a second line with axitinib or everolimus or sorafenib should be considered to improve the clinical outcome of the disease. Up to now there is not a clear evidence of superiority in favour of an agent versus the others available.

At pazopanib failure no evidences are available to support physicians in the decision making in the everyday clinical practice.

Moreover no data are available in third line with a TKi after two previous lines of therapy with TKIs.

This study was designed to evaluate prospectively the efficacy of two different sequences of TKis in third line:

The first (group A) to evaluate the efficacy of sorafenib after two previous lines of TKIs with sunitinib followed by axitinib

The second (group B) to evaluate the efficacy of sunitinib after two previous lines of TKIs with pazopanib followed by sorafenib.

400 mg bid is the standard approved dose for sorafenib in the treatment of mRCC while 50 mg for 4 consecutive weeks every six weeks is the standard dose for sunitinb

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Mi
      • Milan, Mi, Italy, 20156
        • Istituto Tumori

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • Patients with histological diagnosis of Renal Cell Carcinoma (RCC)
  • Measurable disease
  • Previous treatment with two sequences of TKIs including sunitinib followed by axitinib and pazopanib followed by sorafenib.
  • ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1
  • All prognostic group according to Heng criteria
  • Life expectancy of at least 12 weeks.

  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

    • Hemoglobin > or equal to 10.0 g/dl
    • Absolute neutrophil count (ANC) >1,500/mm3
    • Platelet count > or equal to 100,000/ml
    • Total bilirubin ≤ 1.5 times the upper limit of normal
    • ALT (Alanine Transferase) and AST (Aspartate transferase) ≤ 2.5 x upper normal limit (ULN)
    • ALP (Alkaline phosphatase) ≤ 4 x ULN
    • PT-INR/PTT (Protrombine Time; International Normalized Ratio; Partial Tromboplastine Time)≤ 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] For patients on warfarin, close monitoring of at least weekly evaluations will be performed, until INR is stable based on a measurement at pre-dose, as defined by the local standard of care.
  • Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial.
  • Signed informed consent must be obtained prior to any study specific procedures

Exclusion Criteria:

  • Previous treatment for metastatic RCC other than pazopanib followed by sorafenib or sunitinib followed by axitinib
  • History of cardiac disease: congestive heart failure >NYHA class 2 (New York Heart Association); active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension (>= 160 mmHg systolic and/or 90 mmHg diastolic).
  • History of HIV infection
  • Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
  • Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
  • History of organ allograft
  • Patients with evidence or history of bleeding diathesis
  • Patients undergoing renal dyalisis
  • History of other disease, metabolic dysfunction, physical examination findings or clinical laboratory findings giving reasonable suspicion of a disease condition that contraindicates use of an investigational drug or patient at high risk from treatment complications
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 2 years prior to study entry.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Sorafenib or Sunitinib
Sorafenib will be administered at 400 mg bid daily Sunitinib will be administered at 50 mg die orally (4 week on/2 weeks off)
Drug: Sorafenib or Sunitinib
After two lines of TKIs, patients received a third line with sunitinib or sorafenib, according to previous treatments
Other Names:
  • Nexavar or Sutent

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
median progression free survival (mPFS)
Time Frame: up to five years
To evaluate the efficacy of a third TKI after two previous lines of therapy with TKIs, in terms of mPFS; time from the first treatment administration to first disease progression or death (months). It will be evaluated up to five years.
up to five years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
OS (Overall Survival)
Time Frame: up to five years
To evaluate overall survival: time from first treatment to death (months) (up to five years).
up to five years
safety of a third line TKI
Time Frame: up to five years
To evaluate the safety of a third line TKI; it will be evaluated and graded according to NCI-CTC version 3.0 criteria (Common Toxicity Criteria). Adverse events will be registered since treatment starts until end of treatment visit (30 +/- 7 days after end of treatment)
up to five years
Quality of life through specific questionnaire EORTC QLQ-C30
Time Frame: up to five years
up to five years
Quality of life through specific questionnaire FKSI-19
Time Frame: up to five years
up to five years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Giuseppe Procopio, MD, IRCCS Istituto Nazionale Tumori

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 8, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 8, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 11, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 5, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 7, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 7, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 5, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2014-001956-52

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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