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

Metastatic Renal Cell Carcinoma Clinical Trial

— BREAKPOINT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03463681
• Other study ID #: 2018-000582-36
• Status: Completed
• Phase: Phase 2
• Start date: June 11, 2018
• Est. completion date: April 8, 2021

Study information

• Verified date: April 2021
• Source: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: April 8, 2021
• Est. primary completion date: April 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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 ß-human chorionic gonadotropin (ß-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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma

Intervention

Drug:
• Cabometyx
cabozantinib 60 mg orally once daily

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale Tumori	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Cella D, Escudier B, Tannir NM, Powles T, Donskov F, Peltola K, Schmidinger M, Heng DYC, Mainwaring PN, Hammers HJ, Lee JL, Roth BJ, Marteau F, Williams P, Baer J, Mangeshkar M, Scheffold C, Hutson TE, Pal S, Motzer RJ, Choueiri TK. Quality of Life Outcom — View Citation

Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Géczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir — View Citation

Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DYC, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ — View Citation

Choueiri TK, Halabi S, Sanford BL, Hahn O, Michaelson MD, Walsh MK, Feldman DR, Olencki T, Picus J, Small EJ, Dakhil S, George DJ, Morris MJ. Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Po — View Citation

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

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (v — View Citation

Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, C — View Citation

Ref: Brookmeyer, R and Crowley, JJ (1982): A confidence interval for the median survival time. Biometrics 38:29-41

Shah AY, Kotecha RR, Lemke EA, Chandramohan A, Chaim JL, Msaouel P, Xiao L, Gao J, Campbell MT, Zurita AJ, Wang J, Corn PG, Jonasch E, Motzer RJ, Sharma P, Voss MH, Tannir NM. Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with second-line VEGFR-TKI after first-line immune checkpoint inhibitors. Eur J Cancer. 2019 Jun;114:67-75. doi: 10.1016/j.ejca.2019.04.003. Epub 2019 May 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression free survival (PFS)	To assess the progression free survival (PFS) of cabozantinib in patients pretreated with one immunocheckpoint inhibitor (CPI) in monotherapy or in combination	28 month
Secondary	overall survival (OS)	To assess the overall survival (OS)	28 month
Secondary	objective response rates (ORR)	the efficacy based on objective response rates (ORR) according to RECIST 1:1 criteria	28 month
Secondary	safety: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	28 month