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

NCT03456401 | Terminated Phase 2

• 1 other identifier: 2014-001956-52
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Renal Cancer Cell

Outcome Measures

Primary Outcomes (1)

• 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.

  up to five years

Secondary Outcomes (4)

• OS (Overall Survival)

  up to five years

• safety of a third line TKI

  up to five years

• Quality of life through specific questionnaire EORTC QLQ-C30

  up to five years

• Quality of life through specific questionnaire FKSI-19

  up to five years

Study Arms (1)

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)

Drug: Sorafenib or Sunitinib

Interventions

Sorafenib or Sunitinib DRUG

After two lines of TKIs, patients received a third line with sunitinib or sorafenib, according to previous treatments

Also known as: Nexavar or Sutent

Sorafenib or Sunitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Istituto Tumori

Milan, Mi, 20156, Italy

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Sorafenib; Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Pyrroles; Azoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Giuseppe Procopio, MD

  IRCCS Istituto Nazionale Tumori

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2014
• First Posted: March 7, 2018
• Study Start: November 1, 2014
• Primary Completion: November 8, 2017
• Study Completion: November 8, 2017
• Last Updated: March 7, 2018

Record last verified: 2018-03

Locations

IT (1)