Renal Cancer CellPhase 2TOKIONCT03456401
Third Line TKI After 2 TKIs in Patients With mRCC (Tokio Study)
A Phase 2 study testing Sorafenib or Sunitinib in people with Renal Cancer Cell, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cancer Cell
- What is being tested?
- Sorafenib or Sunitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteItaly
- Study dates
- Nov 2014to 8 Nov 2017
- 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
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Conditions
- Renal Cancer Cell
- Being tested
- Sorafenib or Sunitinib
- 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.
Sorafenib or SunitinibDrug
Also called Nexavar or Sutent
After two lines of TKIs, patients received a third line with sunitinib or sorafenib, according to previous treatments
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib or Sunitinib | Other | Sorafenib will be administered at 400 mg bid daily Sunitinib will be administered at 50 mg die orally (4 week on/2 weeks off) Receives: Drug: Sorafenib or Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
median progression free survival (mPFS)
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.
Measured: up to five years
Secondary outcomes (4)
OS (Overall Survival)
To evaluate overall survival: time from first treatment to death (months) (up to five years).
Measured: up to five years
safety of a third line TKI
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)
Measured: up to five years
Quality of life through specific questionnaire EORTC QLQ-C30
Measured: up to five years
Quality of life through specific questionnaire FKSI-19
Measured: up to five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2018
- Study startNov 2014
- Primary completion8 Nov 2017
- Study completion8 Nov 2017
Why it stopped: availability of new and more promising therapeutic agents than expected in the experimentation in question
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cancer CellStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giuseppe Procopio, MD, Study chair, IRCCS Istituto Nazionale Tumori
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03456401
- Sponsor's protocol ID
- 2014-001956-52
- Other IDs
- 2014
- Acronym
- TOKIO
- Status last verified
- Mar 2018
- First submitted
- 11 Nov 2014
- Last updated
- 7 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT03456401
- Acronym / sponsor ID
- TOKIO / 2014-001956-52
- Conditions
- Renal Cancer Cell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: availability of new and more promising therapeutic agents than expected in the experimentation in question
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- 8 Nov 2017 (actual)
- Study completion
- 8 Nov 2017 (actual)
- First posted
- 7 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sorafenib or Sunitinib | Other | Drug: Sorafenib or SunitinibSorafenib will be administered at 400 mg bid daily Sunitinib will be administered at 50 mg die orally (4 week on/2 weeks off) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sorafenib or SunitinibAlso: Nexavar or SutentAfter two lines of TKIs, patients received a third line with sunitinib or sorafenib, according to previous treatments | Drug | Sorafenib or Sunitinib |
Primary outcome
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.
4 secondary outcomes
OS (Overall Survival)
Time frame: up to five years
safety of a third line TKI
Time frame: up to five years
Quality of life through specific questionnaire EORTC QLQ-C30
Time frame: up to five years
Quality of life through specific questionnaire FKSI-19
Time frame: up to five years
Results and safety
The study was stopped early (reason given: availability of new and more promising therapeutic agents than expected in the experimentation in question). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giuseppe Procopio, MD study chair
IRCCS Istituto Nazionale Tumori
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib or Sunitinib in people with Renal Cancer Cell, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
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 17 inclusion and 10 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: stopped early, as of the sponsor's last update on 7 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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 was stopped early (reason given: availability of new and more promising therapeutic agents than expected in the experimentation in question). Results are not available in the source record.
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?
median progression free survival (mPFS) (time frame: up to five years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Mar 2018.