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Non Small Cell Lung CancerPhase 2CRETANCT04131543

Phase II Study With Cabozantinib in Patients With RET Positive NSCLC

A Phase 2 study testing Cabozantinib 20 MG, Cabozantinib 40 MG and Cabozantinib 60 MG in people with Non Small Cell Lung Cancer, run by University of Bologna at 11 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

This study is aimed to explore the antitumor activity, safety and efficacy profile of cabozantinib in pretreated, advanced RET-rearranged non-small cell lung cancer patients Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
Cabozantinib 20 MG, Cabozantinib 40 MG and Cabozantinib 60 MG
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
11 sitesItaly
Study dates
7 Aug 2019to 7 Aug 2022
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Locally advanced, relapsed or metastatic non-small cell lung cancer - stage IIIB/IV according to 7th International Association for the Study of Lung Cancer (IASLC) classification
  • Ability to understand and willingness to sign informed consent prior to initiation of any study procedures.
  • Pathologically (histology or cytology) confirmed diagnosis of non- small cell lung carcinoma.
  • RET gene rearrangement by local laboratory analysis with an approved standard method (FISH or Next Generation Sequencing Panel). An archival tumor sample must be available for central laboratory confirmation.
  • Male or female and = 18 years of age
  • Life expectancy = 12 weeks
Show all 24Show fewer
  • Have progressed after or during at least one standard anticancer treatment
  • Have measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1); clear radiological evidence of disease progression after first-line therapy must be documented; no previous radiotherapy on the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1
  • Subjects must have adequate organ function including the following:
  • Absolute neutrophil count > 1.5 x 10^9/L
  • Platelet count > 100 x 10^9/L
  • Haemoglobin > 90 g/L
  • ALT < 2.5 times the upper limit of normal (ULN)
  • AST < 2.5 times ULN
  • Total bilirubin <1.5 times ULN
  • Creatinine <1.5 times ULN concurrent with creatinine clearance > 50 ml/min (measured or calculated by Cockcroft and Gault equation, confirmation of creatinine clearance is only required when creatinine is > 1.5 times ULN)
  • Lipase < 2.0 times the upper limit of normal (ULN)
  • Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/exclusion criteria
  • Recovered (i.e., = Grade 1 toxicity) from effects of prior anticancer therapy, except alopecia
  • No radiologic or clinical evidence of acute or chronic pancreatitis
  • For Females: must be postmenopausal (defined as amenhorrea = 12 consecutive months) before the screening visit, or are surgically sterile. If they are of childbearing potential, a negative serum pregnancy test obtained within 3 days before starting study treatment has to be documented; furthermore, patients must agree to adopt 2 effective methods of contraception, at the same time, from the time of signing the informed consent form (ICF) through 4 months after the last dose of study drug.
  • For Males: even if surgically sterilized (i.e. post-vasectomy status) agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug.
  • Ability to comply with protocol requirement.

Who cannot join

  • Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization. Systemic treatment with radionuclides within 6 weeks before randomization. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • Previous treatment with cabozantinib.
  • Gastrointestinal disorders likely to interfere with absorption of the study drug.
  • Subjects with gastrointestinal disorders associated with a high risk of perforation of fistula formation.
  • Subjects with active peptic ulcer or with a history of clinically ¿significant GI bleeding within 6 months before the first dose of study treatment.
  • Patients requiring full-dose anticoagulation therapy any time prior to enrollment.
Show all 27Show fewer
  • Current use of aspirin, clopidogrel, ticlopidine.
  • Patients with tumors invading major pulmonary vessels and/or with cavitating pulmonary lesions.
  • Major surgery within the last four weeks. Complete wound healing from major surgery must have occurred 1 month before randomization and from minor surgery at least 10 days before randomization. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Subjects with clinical or radiological signs of pulmonary hemorrhage within 3 months before the first dose of study treatment.
  • Symptomatic CNS or leptomeningeal lesions, not previously treated with radiotherapy.
  • Untreated central nervous system (CNS) or leptomeningeal metastases are allowed if asymptomatic. Patients with symptomatic CNS or leptomeningeal lesions will be allowed to participate in this study if previously treated with radiotherapy and on stable dose of corticosteroids and/or anticonvulsants for > 10 days or not requiring such medication.
  • Radiotherapy must have been completed a minimum of 4 weeks prior to registration, and patients must have recovered from AEs related to radiotherapy to < grade 1 (except alopecia).
  • History of congenital platelet function defect.
  • Patient unable to swallow tablets
  • Corrected QT interval greater than 500 ms (Fridericia formula)
  • Clinically significant, uncontrolled heart diseases:
  • Unstable angina within 6 months prior to screening
  • Myocardial infarction within 6 months prior to screening
  • History of documented congestive heart failure
  • Uncontrolled hypertension defined by a Systolic Blood Pressure , with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening
  • Ventricular arrhythmias, Supraventricular and nodal arrhythmias not controlled with medication
  • Congenital history of QT syndrome.
  • Diagnosed with or treated for another malignancy within 3 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type may be enrolled in the study if they have undergone complete resection and no evidence of active disease is present.
  • Any type of systemic anticancer agent within 3 weeks of first dose of study treatment, or within 5 half- lives of the agent whichever is shorter (subjects on LHRH or GnRH agonists may be maintained on these agents)
  • Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • Rare hereditary problems of

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Italy11 sites, 11 recruiting

  • OU di Oncologia Medica- Azienda ospedaliero-Universitaria S. Orsola Malpighi

    Bologna, 40138

    Andrea Ardizzoni, MD, 0512142206, andrea.ardizzoni2@unibo.it

    Giada Grilli, MD, 0512142204, giada.grilli2@unibo.it

    Recruiting

  • U.O di Oncologia Medica Policlinico V.Emanuele-G.Rodolico

    Catania, 95125

    Hector Soto Parra, DM, 953782426, hsotoparra@yahoo.it

    Hector Soto Parra, DM

    Not yet recruiting

  • Oncologia Medica 2 -Policlinico San Martino

    Genova, 16132

    Carlo Genova, DN, 0105558918, carlo.genova@hsanmartino.it

    Carlo Genova, DM

    Not yet recruiting

  • S.S. di Oncologia Medica toraco-polmonare - Fondazione IRCCS - Istituto Nazionale Tumori

    Milan, 20133

    Marina Chiara Garassino, DM, +390223903813, marina.garassino@istitutotumori.mi.it

    Linda Pallavicini, +390223903836, linda.pallavicini@istitutotumori.mi.it

    Not yet recruiting

  • U.O.C Pneumologia ad Indirizzo Oncologico -AORN Ospedali dei Colli Monaldi-Cotugno-CTO

    Naples, 80131

    Danilo Rocco, DM, clinicaltrialsrocco@gmail.com

    Danilo Rocco, DM

    Not yet recruiting

  • UOC di Oncologia Medica 2 - IOV Istituto Oncologico Veneto

    Padova, 35128

    Giulia Pasello, DM, 0498215931, giulia.pasello@ioveneto.it

    Raffaella Verrienti, 0498215608, raffaella.verrienti@ioveneto.it

    Not yet recruiting

  • UOC di Oncologia Medica- Azienda Ospidaliero Universitaria di Parma

    Parma, 43126

    Marcello Tiseo, DM, 052170266061, mtiseo@ao.pr.it

    Roberta Camisa, 052170266061, rcamisa@ao.pr.it

    Not yet recruiting

  • US di Oncologia Medica - A.O. di Perugia

    Perugia, 06132

    Fausto Roila, DM, 0755784099, roila.fausto@libero.it

    Fausto Roila, DM

    Not yet recruiting

  • UO Pneumologia - A.O.U Pisana

    Pisa, 56126

    Antonio Chella, DM, +3950996653, anto.kell@tiscali.it

    Antonio Chella, DM

    Not yet recruiting

  • S.C. di Oncologia Medica - IFO - Istituto Regina Elena

    Roma, 00144

    Sabrina Vari, DM, +39-06-52662752, sabrina.vari@ifo.gov.it

    Sonia Borrelli, +39-06-52662752, sonia.borrelli@ifo.gov.it

    Not yet recruiting

  • UOC di Oncologia Medica - Azienda Sanitaria Universitaria Integrata di Udine

    Udine, 33100

    Ciro Rossetto, dm, +39432559330, cirorossetto@asuiud.sanita.fvg.it

    Ciro Rossetto, DM

    Not yet recruiting

Other trials in Italy

About this study

Official title: "Phase II Study to Evaluate the Activity and Safety of Cabozantinib in Pretreated, Advanced RET-rearranged Non-small Cell Lung Cancer Patients: CRETA Trial"

This study is aimed to explore the antitumor activity, safety and efficacy profile of cabozantinib in pretreated, advanced RET-rearranged non-small cell lung cancer patients

Being tested
Cabozantinib 20 MG, Cabozantinib 40 MG, Cabozantinib 60 MG
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • Cabozantinib 20 MGDrug

    Also called CABOMETYX

    Cabozantinib will be administered orally at a (starting) dose of 60 mg once daily. The drug is taken continuously over a period of 28 days (4 weeks), which constitutes one treatment cycle. In all subjects, dose reductions (40mg 20mg) and delays to manage toxicity.

  • Cabozantinib 40 MGDrug

    Also called CABOMETYX

    Cabozantinib will be administered orally at a (starting) dose of 60 mg once daily. The drug is taken continuously over a period of 28 days (4 weeks), which constitutes one treatment cycle. In all subjects, dose reductions (40mg 20mg) and delays to manage toxicity.

  • Cabozantinib 60 MGDrug

    Also called CABOMETYX

    Cabozantinib will be administered orally at a (starting) dose of 60 mg once daily. The drug is taken continuously over a period of 28 days (4 weeks), which constitutes one treatment cycle. In all subjects, dose reductions and delays to manage toxicity. Cabozantinib should be taken in fasting condition with no food for at least 2 hours before and 1 hour after taking the tablets. A high fat meal significantly increased the median tmax to 6 hours from 4 hours (fasted). The treatment will be continued until disease progression, intolerable toxicity, patient refusal or Investigator's decision or any criterion for withdrawal from the trial or trial drug is fulfilled.

Study groups in NCT04131543
Study groupRoleWhat they receive
CabozantinibExperimentalCabozantinib will be administered orally at a (starting) dose of 60 mg once daily. The drug is taken continuously over a period of 28 days (4 weeks), which constitutes one treatment cycle. In all subjects, dose reductions and delays to manage toxicity. Cabozantinib should be taken in fasting condition with no food for at least 2 hours before and 1 hour after taking the tablets. A high fat meal significantly increased the median tmax to 6 hours from 4 hours (fasted). The treatment will be continued until disease progression, intolerable toxicity, patient refusal or Investigator's decision or any criterion for withdrawal from the trial or trial drug is fulfilled.
Receives: Drug: Cabozantinib 20 MG; Drug: Cabozantinib 40 MG; Drug: Cabozantinib 60 MG

What is being measured

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

  1. Response Rate (RR)

    Exact binomial method will be used to estimate the response rate (CR+PR) and its 95% confidence interval.Proportion of patients presenting Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) based on the Investigator's assessment according to standard RECIST criteria v1.1. Patients with no tumor assessment after baseline will be classified as non-responders.

    Measured: From the start of treatment ( Baseline) to the progression of Disease (PD) or trial discontinuation whichever occurs first, assessed up to 24 months

Secondary outcomes (5)

  1. Toxicity (frequency of adverse events)

    the assessment of safety will be based mainly on the frequency of adverse events; toxicity will be measured according to NCI Common Toxicity Criteria Adverse Event (CTCAE), version 4.03.

    Measured: From the start of treatment ( Baseline) to the progression of Disease (PD) or trial discontinuation whichever occurs first, assessed up to 24 months

  2. Progression-Free Survival (PFS)

    PFS will be calculated from the first treatment intake to the date of progressive disease, or death.

    Measured: From the start of treatment ( Baseline) to the progression of Disease (PD) or trial discontinuation whichever occurs first, assessed up to 24 months

  3. Overall survival (OS)

    OS will be calculated from the first treatment intake to death from any cause.

    Measured: From the start of treatment ( Baseline) to the progression of Disease (PD) or trial discontinuation whichever occurs first, assessed up to 24 months

  4. Duration of response (DOR

    DOR will be calculated from the first treatment intake to the date of disease progression or death.

    Measured: From the start of treatment ( Baseline) to the progression of Disease (PD) or trial discontinuation whichever occurs first, assessed up to 24 months

  5. Disease Control Rate(DCR)

    DCR will be measured as the sum of complete and partial responses + stable disease.

    Measured: From the start of treatment ( Baseline) to the progression of Disease (PD) or trial discontinuation whichever occurs first, assessed up to 24 months

Timeline

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

  1. First posted18 Oct 2019
  2. Study start7 Aug 2019
  3. Primary completion7 Aug 2020 (estimated)
  4. Study completion7 Aug 2022 (estimated)

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
Model description
Single-arm, ope label clinical trial
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04131543
Sponsor's protocol ID
CRETA
Acronym
CRETA
Status last verified
Oct 2019
First submitted
26 Sep 2019
Last updated
18 Oct 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010 Dec 15;127(12):2893-917. doi: 10.1002/ijc.25516.

    PubMed 21351269

  • Masters GA, Temin S, Azzoli CG, Giaccone G, Baker S Jr, Brahmer JR, Ellis PM, Gajra A, Rackear N, Schiller JH, Smith TJ, Strawn JR, Trent D, Johnson DH; American Society of Clinical Oncology Clinical Practice. Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015 Oct 20;33(30):3488-515. doi: 10.1200/JCO.2015.62.1342. Epub 2015 Aug 31.

    PubMed 26324367

  • Zbuk KM, Eng C. Cancer phenomics: RET and PTEN as illustrative models. Nat Rev Cancer. 2007 Jan;7(1):35-45. doi: 10.1038/nrc2037. Epub 2006 Dec 14.

    PubMed 17167516

  • Grieco M, Santoro M, Berlingieri MT, Melillo RM, Donghi R, Bongarzone I, Pierotti MA, Della Porta G, Fusco A, Vecchio G. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell. 1990 Feb 23;60(4):557-63. doi: 10.1016/0092-8674(90)90659-3.

    PubMed 2406025

  • Bongarzone I, Vigneri P, Mariani L, Collini P, Pilotti S, Pierotti MA. RET/NTRK1 rearrangements in thyroid gland tumors of the papillary carcinoma family: correlation with clinicopathological features. Clin Cancer Res. 1998 Jan;4(1):223-8.

    PubMed 9516975

  • Wang R, Hu H, Pan Y, Li Y, Ye T, Li C, Luo X, Wang L, Li H, Zhang Y, Li F, Lu Y, Lu Q, Xu J, Garfield D, Shen L, Ji H, Pao W, Sun Y, Chen H. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol. 2012 Dec 10;30(35):4352-9. doi: 10.1200/JCO.2012.44.1477. Epub 2012 Nov 13.

    PubMed 23150706

  • Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T, Sakamoto H, Tsuta K, Furuta K, Shimada Y, Iwakawa R, Ogiwara H, Oike T, Enari M, Schetter AJ, Okayama H, Haugen A, Skaug V, Chiku S, Yamanaka I, Arai Y, Watanabe S, Sekine I, Ogawa S, Harris CC, Tsuda H, Yoshida T, Yokota J, Shibata T. KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 2012 Feb 12;18(3):375-7. doi: 10.1038/nm.2644.

    PubMed 22327624

  • Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, Donahue A, Downing SR, Frampton GM, Garcia L, Juhn F, Mitchell KC, White E, White J, Zwirko Z, Peretz T, Nechushtan H, Soussan-Gutman L, Kim J, Sasaki H, Kim HR, Park SI, Ercan D, Sheehan CE, Ross JS, Cronin MT, Janne PA, Stephens PJ. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012 Feb 12;18(3):382-4. doi: 10.1038/nm.2673.

    PubMed 22327622

  • Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H, Ishikawa Y. RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012 Feb 12;18(3):378-81. doi: 10.1038/nm.2658.

    PubMed 22327623

  • Plaza-Menacho I, Mologni L, McDonald NQ. Mechanisms of RET signaling in cancer: current and future implications for targeted therapy. Cell Signal. 2014 Aug;26(8):1743-52. doi: 10.1016/j.cellsig.2014.03.032. Epub 2014 Apr 3.

    PubMed 24705026

  • Drilon A, Wang L, Hasanovic A, Suehara Y, Lipson D, Stephens P, Ross J, Miller V, Ginsberg M, Zakowski MF, Kris MG, Ladanyi M, Rizvi N. Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov. 2013 Jun;3(6):630-5. doi: 10.1158/2159-8290.CD-13-0035. Epub 2013 Mar 26.

    PubMed 23533264

  • Michels S, Scheel AH, Scheffler M, Schultheis AM, Gautschi O, Aebersold F, Diebold J, Pall G, Rothschild S, Bubendorf L, Hartmann W, Heukamp L, Schildhaus HU, Fassunke J, Ihle MA, Kunstlinger H, Heydt C, Fischer R, Nogova L, Mattonet C, Hein R, Adams A, Gerigk U, Schulte W, Luders H, Grohe C, Graeven U, Muller-Naendrup C, Draube A, Kambartel KO, Kruger S, Schulze-Olden S, Serke M, Engel-Riedel W, Kaminsky B, Randerath W, Merkelbach-Bruse S, Buttner R, Wolf J. Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients. J Thorac Oncol. 2016 Jan;11(1):122-7. doi: 10.1016/j.jtho.2015.09.016.

    PubMed 26762747

  • Gautschi O, Zander T, Keller FA, Strobel K, Hirschmann A, Aebi S, Diebold J. A patient with lung adenocarcinoma and RET fusion treated with vandetanib. J Thorac Oncol. 2013 May;8(5):e43-4. doi: 10.1097/JTO.0b013e31828a4d07. No abstract available.

    PubMed 23584301

  • Kodama T, Tsukaguchi T, Satoh Y, Yoshida M, Watanabe Y, Kondoh O, Sakamoto H. Alectinib shows potent antitumor activity against RET-rearranged non-small cell lung cancer. Mol Cancer Ther. 2014 Dec;13(12):2910-8. doi: 10.1158/1535-7163.MCT-14-0274. Epub 2014 Oct 27.

    PubMed 25349307

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib 20 MG, Cabozantinib 40 MG and Cabozantinib 60 MG in people with Non Small Cell Lung Cancer, run by University of Bologna at 11 sites 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 24 inclusion and 27 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: status not confirmed, as of the sponsor's last update on 18 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites 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?

Results are not available in the source record.

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

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response Rate (RR) (time frame: From the start of treatment ( Baseline) to the progression of Disease (PD) or trial discontinuation whichever occurs first, assessed up to 24 months). 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 NCT04131543, which also lists 21 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 18 Oct 2019.

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