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

NCT ID: NCT03463681

Last Updated: 2021-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-11
• Study Completion Date: 2021-04-08

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

Conditions

Metastatic Renal Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cabozantinib

all subjects will recieve open label Cabozantinib 60 mg orally once daily

Group Type: EXPERIMENTAL

Cabometyx

Intervention Type: DRUG

cabozantinib 60 mg orally once daily

Interventions

Cabometyx

cabozantinib 60 mg orally once daily

Intervention Type: DRUG

Other Intervention Names

cabozantinib

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giuseppe Procopio, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS ISTITUTO NAZIONALE TUMORI

Locations

Fondazione IRCCS Istituto Nazionale Tumori

Milan, , Italy

Countries

Italy

References

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

Reference Type: BACKGROUND

Shah A, Lemke E, Gao J et al, Outcomes of patients with metastatic clear cell renal cell carcinoma treated with second line vascular endothelial growth factor receptor tyrosine kinase inhibitors after first line immune checkpoint inhibitors; Genitourinary Cancer Symposium 2018, abstract 682.

Reference Type: BACKGROUND

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

Reference Type: BACKGROUND

Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Geczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ; METEOR Investigators. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. doi: 10.1056/NEJMoa1510016. Epub 2015 Sep 25.

Reference Type: RESULT

PMID: 26406150 (View on PubMed)

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; METEOR investigators. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-927. doi: 10.1016/S1470-2045(16)30107-3. Epub 2016 Jun 5.

Reference Type: RESULT

PMID: 27279544 (View on PubMed)

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 Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. J Clin Oncol. 2017 Feb 20;35(6):591-597. doi: 10.1200/JCO.2016.70.7398. Epub 2016 Nov 14.

Reference Type: RESULT

PMID: 28199818 (View on PubMed)

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 (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

Reference Type: RESULT

PMID: 19097774 (View on PubMed)

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 Outcomes for Cabozantinib Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma: METEOR Phase III Randomized Trial. J Clin Oncol. 2018 Mar 10;36(8):757-764. doi: 10.1200/JCO.2017.75.2170. Epub 2018 Jan 29.

Reference Type: RESULT

PMID: 29377755 (View on PubMed)

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, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. doi: 10.1056/NEJMoa1303989.

Reference Type: RESULT

PMID: 23964934 (View on PubMed)

Procopio G, Claps M, Pircher C, Porcu L, Sepe P, Guadalupi V, De Giorgi U, Bimbatti D, Nole F, Carrozza F, Buti S, Iacovelli R, Ciccarese C, Masini C, Baldessari C, Doni L, Cusmai A, Gernone A, Scagliarini S, Pignata S, de Braud F, Verzoni E. A multicenter phase 2 single arm study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pre-treated with one immune-checkpoint inhibitor: The BREAKPOINT trial (Meet-Uro trial 03). Tumori. 2023 Feb;109(1):129-137. doi: 10.1177/03008916221138881. Epub 2022 Nov 29.

Reference Type: DERIVED

PMID: 36447337 (View on PubMed)

Other Identifiers

2018-000582-36

Identifier Type: -

Identifier Source: org_study_id