Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of CaBozantinib in Patients With Advanced or Unresectable Renal cEll cArcinoma (BREAKPOINT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03463681
Recruitment Status : Recruiting
First Posted : March 13, 2018
Last Update Posted : October 18, 2019
Sponsor:
Information provided by (Responsible Party):
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Brief Summary:
This is an open label single arm, multicenter, phase II study designet To assess the progression free survival (PFS) of cabozantinib in patients pretreated with one immunocheckpoint inhibitor (CPI) in monotherapy or in combination

Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Carcinoma Drug: Cabometyx Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 49 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open Label Study of CaBozantinib in Patients With Advanced or Unresectable Renal cEll cArcinoma Pretreated With One immunochecKPOint INhibiTor (Anti PD1/PDL1): the BREAKPOINT Trial
Actual Study Start Date : June 11, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: Cabozantinib
all subjects will recieve open label Cabozantinib 60 mg orally once daily
Drug: Cabometyx
cabozantinib 60 mg orally once daily
Other Name: cabozantinib




Primary Outcome Measures :
  1. progression free survival (PFS) [ Time Frame: 28 month ]
    To assess the progression free survival (PFS) of cabozantinib in patients pretreated with one immunocheckpoint inhibitor (CPI) in monotherapy or in combination


Secondary Outcome Measures :
  1. overall survival (OS) [ Time Frame: 28 month ]
    To assess the overall survival (OS)

  2. objective response rates (ORR) [ Time Frame: 28 month ]
    the efficacy based on objective response rates (ORR) according to RECIST 1:1 criteria

  3. safety: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 28 month ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written informed consent
  2. One previous anticancer treatment with a PD1/PDL1 inhibitor, as monotherapy or in combination with an angiogenesis inhibitor or anti CTLA 4, in both setting first line or adjuvant ( in this case patient having recurrence during the adjuvant treatment or within 6 months after therapy with PD1-PD-L1 therapy)
  3. Age ≥18 years
  4. Patients with histological diagnosis of predominant clear cells renal cell carcinoma
  5. Measurable disease (as per RECIST 1.1 criteria) with documented radiological progression
  6. Fertile women (<2 years after last menstruation) and men of childbearing potential must use effective methods of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgical sterilisation) during the study and for 4 months after the last dose of study treatment
  7. All sites of disease including brain metastases (non symptomatic)
  8. Karnofsky performance status ≥ 70%
  9. Life expectancy greater than 3 months
  10. The required values at baseline are as follows:

    • Absolute neutrophil count >1.5 x 109 /L,
    • Platelet count > 100 x 109 /L,
    • Haemoglobin > 9g/dl,
    • Total bilirubin < 1.5 upper limit of normal (ULN);
    • AST, ALT<2.5 ULN in patients without liver metastases, <5 ULN in patients with liver metastases;
    • serum creatinine < 2.0 mg/dl, amylase and lipase <1.5 ULN 11- Female subjects of childbearing potential must not be pregnant at screening

Exclusion Criteria:

  1. Major surgical procedure within 28 days prior to study treatment start
  2. Other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix, meningiomas)
  3. Clinically significant cardiovascular disease, for example cerebrovascular accidents (<6 months), myocardial infarction (<6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication
  4. Recent (within the 30 days prior to randomisation) treatment with another investigational drug or participation in another investigational study
  5. Symptomatic brain metastasis
  6. History of other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease condition that contraindicates use of an investigational drug or patient at high risk from treatment complications
  7. PT or INR and PTT >1.5 times the Upper Normal Limit of the institution (patient who are being therapeutically anticoagulated with an agent such as warfarin 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
  8. Previous or concomitant radiotherapy in the lesion parameter of disease
  9. Previous radiotherapy or other locoregional antitumoral treatment performed within 21 days before the study recruitment
  10. Uncontrolled hypertension (>= 160 mmHg systolic and/or 90 mmHg diastolic) while receiving chronic medication
  11. Inability to swallow tablets or capsules
  12. Female subject who is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women
  13. Known history of human immunodeficiency virus (HIV) infection, active hepatitis B, or active hepatitis C.
  14. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03463681


Contacts
Layout table for location contacts
Contact: Giuseppe Procopio, MD +390223904450 giuseppe.procopio@istitutotumori.mi.it
Contact: Rosanna Montone, Dr.ssa +390223903817 rosanna.montone@istitutotumori.mi.it

Locations
Layout table for location information
Italy
Fondazione IRCCS Istituto Nazionale Tumori Recruiting
Milan, Italy, 20133
Contact: Giuseppe Procopio, MD    +390223904450    giuseppe.procopio@istitutotumori.mi.it   
Contact: Rosanna Montone, Dr.ssa    +390223903817    rosanna.montone@istitutotumori.mi.it   
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
Layout table for investigator information
Principal Investigator: Giuseppe Procopio, MD Fondazione IRCCS Istituto Nazionale Tumori
Publications of Results:

Other Publications:
Derosa L, Rouche JA, Colomba E et al. Efficacy of cabozantinib after PD1/PDL1 checkpoint inhibitors in metastatic renal cell carcinoma (mRCC): the gustave Roussy experience. Ann of Onc vol 28, sep 2017
Ref: Brookmeyer, R and Crowley, JJ (1982): A confidence interval for the median survival time. Biometrics 38:29-41

Layout table for additonal information
Responsible Party: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier: NCT03463681    
Other Study ID Numbers: 2018-000582-36
First Posted: March 13, 2018    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases