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

NCT03463681 | Completed Phase 2

• 1 other identifier: 2018-000582-36
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• overall survival (OS)

  28 month

• objective response rates (ORR)

  28 month

• safety: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  28 month

Study Arms (1)

Cabozantinib

EXPERIMENTAL

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

Drug: Cabometyx

Interventions

Cabometyx DRUG

cabozantinib 60 mg orally once daily

Also known as: cabozantinib

Cabozantinib

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• 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)
• Age ≥18 years
• Patients with histological diagnosis of predominant clear cells renal cell carcinoma
• Measurable disease (as per RECIST 1.1 criteria) with documented radiological progression
• 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
• All sites of disease including brain metastases (non symptomatic)
• Karnofsky performance status ≥ 70%
• Life expectancy greater than 3 months
• 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;

You may not qualify if:

• Major surgical procedure within 28 days prior to study treatment start
• 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)
• 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
• Recent (within the 30 days prior to randomisation) treatment with another investigational drug or participation in another investigational study
• Symptomatic brain metastasis
• 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
• 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
• Previous or concomitant radiotherapy in the lesion parameter of disease
• Previous radiotherapy or other locoregional antitumoral treatment performed within 21 days before the study recruitment
• Uncontrolled hypertension (\>= 160 mmHg systolic and/or 90 mmHg diastolic) while receiving chronic medication
• Inability to swallow tablets or capsules
• 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
• Known history of human immunodeficiency virus (HIV) infection, active hepatitis B, or active hepatitis C.
• Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale Tumori

Milan, 20133, Italy

Location

Related Publications (10)

• 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

  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.

  BACKGROUND

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

  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.

  PMID: 26406150 RESULT

• 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.

  PMID: 27279544 RESULT

• 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.

  PMID: 28199818 RESULT

• 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.

  PMID: 19097774 RESULT

• 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.

  PMID: 29377755 RESULT

• 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.

  PMID: 23964934 RESULT

• 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.

  PMID: 36447337 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

cabozantinib

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

Study Officials

• Giuseppe Procopio, MD

  Fondazione IRCCS ISTITUTO NAZIONALE TUMORI

  PRINCIPAL INVESTIGATOR

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: March 5, 2018
• First Posted: March 13, 2018
• Study Start: June 11, 2018
• Primary Completion: April 8, 2021
• Study Completion: April 8, 2021
• Last Updated: April 26, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)