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Metastatic Renal Cell CarcinomaPhase 2BREAKPOINTNCT03463681

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

A Phase 2 study testing Cabometyx in people with Metastatic Renal Cell Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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 Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
Cabometyx
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
1 siteItaly
Study dates
11 Jun 2018to 8 Apr 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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;
  • serum creatinine < 2.0 mg/dl, amylase and lipase <1.5 ULN 11- Female subjects of childbearing potential must not be pregnant at screening

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Fondazione IRCCS Istituto Nazionale Tumori

    Milan, 20133

Other trials in Italy

About this study

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

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

Being tested
Cabometyx
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabometyxDrug

    Also called cabozantinib

    cabozantinib 60 mg orally once daily

Study groups in NCT03463681
Study groupRoleWhat they receive
CabozantinibExperimentalall subjects will recieve open label Cabozantinib 60 mg orally once daily
Receives: Drug: Cabometyx

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 28 month

Secondary outcomes (3)

  1. overall survival (OS)

    To assess the overall survival (OS)

    Measured: 28 month

  2. objective response rates (ORR)

    the efficacy based on objective response rates (ORR) according to RECIST 1:1 criteria

    Measured: 28 month

  3. 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

    Measured: 28 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2018
  2. Study start11 Jun 2018
  3. Primary completion8 Apr 2021
  4. Study completion8 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03463681
Sponsor's protocol ID
2018-000582-36
Other IDs
2018
Acronym
BREAKPOINT
Status last verified
Apr 2021
First submitted
5 Mar 2018
Last updated
26 Apr 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

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

  • 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.

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

  • 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.

    PubMed 26406150

  • 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.

    PubMed 27279544

  • 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.

    PubMed 28199818

  • 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.

    PubMed 19097774

  • 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.

    PubMed 29377755

  • 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.

    PubMed 23964934

  • 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.

    PubMed 36447337

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabometyx in people with Metastatic Renal Cell Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

progression free survival (PFS) (time frame: 28 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03463681, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2021.

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