NCT04131543

Brief 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

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
25

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Aug 2019

Typical duration for phase_2

Geographic Reach
1 country

11 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 7, 2019

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 26, 2019

Completed
22 days until next milestone

First Posted

Study publicly available on registry

October 18, 2019

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 7, 2020

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 7, 2022

Completed
Last Updated

October 18, 2019

Status Verified

October 1, 2019

Enrollment Period

1 year

First QC Date

September 26, 2019

Last Update Submit

October 17, 2019

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (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.

    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)

  • Toxicity (frequency of adverse events)

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

  • Progression-Free Survival (PFS)

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

  • Overall survival (OS)

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

  • Duration of response (DOR

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

  • Disease Control Rate(DCR)

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

Other Outcomes (2)

  • RET aberration

    On the start of treatment (Baseline) and through study completion, an average of 1 year

  • RET-rearrangment on tumor tissue

    At the start of treatment (baseline)

Study Arms (1)

Cabozantinib

EXPERIMENTAL

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.

Drug: Cabozantinib 20 MGDrug: Cabozantinib 40 MGDrug: Cabozantinib 60 MG

Interventions

Cabozantinib 20 MGDRUG

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.

Also known as: CABOMETYX
Cabozantinib
Cabozantinib 40 MGDRUG

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.

Also known as: CABOMETYX
Cabozantinib
Cabozantinib 60 MGDRUG

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.

Also known as: CABOMETYX
Cabozantinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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
  • +3 more criteria

You may not qualify if:

  • 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.
  • 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.
  • 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.
  • +17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

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

Bologna, 40138, Italy

RECRUITING

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

Catania, 95125, Italy

NOT YET RECRUITING

Oncologia Medica 2 -Policlinico San Martino

Genova, 16132, Italy

NOT YET RECRUITING

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

Milan, 20133, Italy

NOT YET RECRUITING

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

Napoli, 80131, Italy

NOT YET RECRUITING

UOC di Oncologia Medica 2 - IOV Istituto Oncologico Veneto

Padua, 35128, Italy

NOT YET RECRUITING

UOC di Oncologia Medica- Azienda Ospidaliero Universitaria di Parma

Parma, 43126, Italy

NOT YET RECRUITING

US di Oncologia Medica - A.O. di Perugia

Perugia, 06132, Italy

NOT YET RECRUITING

UO Pneumologia - A.O.U Pisana

Pisa, 56126, Italy

NOT YET RECRUITING

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

Roma, 00144, Italy

NOT YET RECRUITING

UOC di Oncologia Medica - Azienda Sanitaria Universitaria Integrata di Udine

Udine, 33100, Italy

NOT YET RECRUITING

Related Publications (21)

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    PMID: 21351269RESULT

  • 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.

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  • 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.

    PMID: 17167516RESULT

  • 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.

    PMID: 2406025RESULT

  • 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.

    PMID: 9516975RESULT

  • 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.

    PMID: 23150706RESULT

  • 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.

    PMID: 22327624RESULT

  • 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.

    PMID: 22327622RESULT

  • 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.

    PMID: 22327623RESULT

  • 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.

    PMID: 24705026RESULT

  • 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.

    PMID: 23533264RESULT

  • 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.

    PMID: 26762747RESULT

  • 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.

    PMID: 23584301RESULT

  • 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.

    PMID: 25349307RESULT

  • 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: 26406150RESULT

  • 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: 27279544RESULT

  • 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: 28199818RESULT

  • Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23.

    PMID: 21606412RESULT

  • Vergote IB, Smith DC, Berger R, Kurzrock R, Vogelzang NJ, Sella A, Wheler J, Lee Y, Foster PG, Weitzman R, Buckanovich RJ. A phase 2 randomised discontinuation trial of cabozantinib in patients with ovarian carcinoma. Eur J Cancer. 2017 Sep;83:229-236. doi: 10.1016/j.ejca.2017.06.018. Epub 2017 Jul 26.

    PMID: 28755607RESULT

  • Mukhopadhyay S, Pennell NA, Ali SM, Ross JS, Ma PC, Velcheti V. RET-rearranged lung adenocarcinomas with lymphangitic spread, psammoma bodies, and clinical responses to cabozantinib. J Thorac Oncol. 2014 Nov;9(11):1714-9. doi: 10.1097/JTO.0000000000000323.

    PMID: 25436805RESULT

  • Drilon A, Rekhtman N, Arcila M, Wang L, Ni A, Albano M, Van Voorthuysen M, Somwar R, Smith RS, Montecalvo J, Plodkowski A, Ginsberg MS, Riely GJ, Rudin CM, Ladanyi M, Kris MG. Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial. Lancet Oncol. 2016 Dec;17(12):1653-1660. doi: 10.1016/S1470-2045(16)30562-9. Epub 2016 Nov 4.

    PMID: 27825636RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: Single-arm, ope label clinical trial
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor/MD

Study Record Dates

First Submitted

September 26, 2019

First Posted

October 18, 2019

Study Start

August 7, 2019

Primary Completion

August 7, 2020

Study Completion

August 7, 2022

Last Updated

October 18, 2019

Record last verified: 2019-10

Locations

IT(11)