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Phase II Study With Cabozantinib in Patients With RET Positive NSCLC (CRETA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04131543
Recruitment Status : Unknown
Verified October 2019 by Andrea Ardizzoni, University of Bologna.
Recruitment status was:  Recruiting
First Posted : October 18, 2019
Last Update Posted : October 18, 2019
Sponsor:
Collaborators:
AOU S.Orsola Malpighi-Unit of Oncologic Molecular and Transplantations Pathology
Bioikos Ambiente Srl
Ipsen
Mipharm SpA
Information provided by (Responsible Party):
Andrea Ardizzoni, University of Bologna

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

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: Cabozantinib 20 MG Drug: Cabozantinib 40 MG Drug: Cabozantinib 60 MG Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single-arm, ope label clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
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"
Actual Study Start Date : August 7, 2019
Estimated Primary Completion Date : August 7, 2020
Estimated Study Completion Date : August 7, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Cabozantinib
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 MG
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.
Other Name: CABOMETYX

Drug: Cabozantinib 40 MG
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.
Other Name: CABOMETYX

Drug: Cabozantinib 60 MG
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.
Other Name: CABOMETYX




Primary Outcome Measures :
  1. 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 ]
    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.


Secondary Outcome Measures :
  1. Toxicity (frequency of adverse events) [ 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 ]
    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.

  2. Progression-Free Survival (PFS) [ 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 ]
    PFS will be calculated from the first treatment intake to the date of progressive disease, or death.

  3. Overall survival (OS) [ 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 ]
    OS will be calculated from the first treatment intake to death from any cause.

  4. Duration of response (DOR [ 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 ]
    DOR will be calculated from the first treatment intake to the date of disease progression or death.

  5. Disease Control Rate(DCR) [ 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 ]
    DCR will be measured as the sum of complete and partial responses + stable disease.


Other Outcome Measures:
  1. RET aberration [ Time Frame: On the start of treatment (Baseline) and through study completion, an average of 1 year ]
    Detection of RET aberration on DNA extracted from circulating tumor cells (CTCs) isolated in blood at baseline (optional)

  2. RET-rearrangment on tumor tissue [ Time Frame: At the start of treatment (baseline) ]
    Archival tumor tissue (FFPE tumor block or 7-10 unstained slides) will be assessed for determination of RET-rearrangment on tumor cells by using A FISH evaluation of the translocation will be performed using a break-apart probe for the 10p11 locus.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. Ability to understand and willingness to sign informed consent prior to initiation of any study procedures.
  3. Pathologically (histology or cytology) confirmed diagnosis of non- small cell lung carcinoma.
  4. 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.
  5. Male or female and = 18 years of age
  6. Life expectancy = 12 weeks
  7. Have progressed after or during at least one standard anticancer treatment
  8. 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
  9. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1
  10. 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)
  11. 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
  12. Recovered (i.e., = Grade 1 toxicity) from effects of prior anticancer therapy, except alopecia
  13. No radiologic or clinical evidence of acute or chronic pancreatitis
  14. 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.
  15. 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.
  16. Ability to comply with protocol requirement.

Exclusion criteria:

  1. 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.
  2. Previous treatment with cabozantinib.
  3. Gastrointestinal disorders likely to interfere with absorption of the study drug.
  4. Subjects with gastrointestinal disorders associated with a high risk of perforation of fistula formation.
  5. Subjects with active peptic ulcer or with a history of clinically ¿significant GI bleeding within 6 months before the first dose of study treatment.
  6. Patients requiring full-dose anticoagulation therapy any time prior to enrollment.
  7. Current use of aspirin, clopidogrel, ticlopidine.
  8. Patients with tumors invading major pulmonary vessels and/or with cavitating pulmonary lesions.
  9. 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.
  10. Subjects with clinical or radiological signs of pulmonary hemorrhage within 3 months before the first dose of study treatment.
  11. 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).

  12. History of congenital platelet function defect.
  13. Patient unable to swallow tablets
  14. Corrected QT interval greater than 500 ms (Fridericia formula)
  15. 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.
  16. 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.
  17. 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)
  18. 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.
  19. Rare hereditary problems of

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04131543


Locations
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Italy
OU di Oncologia Medica- Azienda ospedaliero-Universitaria S. Orsola Malpighi Recruiting
Bologna, Italy, 40138
Contact: Andrea Ardizzoni, MD    0512142206    andrea.ardizzoni2@unibo.it   
Contact: Giada Grilli, MD    0512142204    giada.grilli2@unibo.it   
Principal Investigator: Andrea Ardizzoni, DM         
Sub-Investigator: Francesco Gelsomino, DM         
Sub-Investigator: Karim Rihawi, DM         
U.O di Oncologia Medica Policlinico V.Emanuele-G.Rodolico Not yet recruiting
Catania, Italy, 95125
Contact: Hector Soto Parra, DM    953782426    hsotoparra@yahoo.it   
Principal Investigator: Hector Soto Parra, DM         
Oncologia Medica 2 -Policlinico San Martino Not yet recruiting
Genova, Italy, 16132
Contact: Carlo Genova, DN    0105558918    carlo.genova@hsanmartino.it   
Principal Investigator: Carlo Genova, DM         
S.S. di Oncologia Medica toraco-polmonare - Fondazione IRCCS - Istituto Nazionale Tumori Not yet recruiting
Milano, Italy, 20133
Contact: Marina Chiara Garassino, DM    +390223903813    marina.garassino@istitutotumori.mi.it   
Contact: Linda Pallavicini    +390223903836    linda.pallavicini@istitutotumori.mi.it   
Principal Investigator: Marina Chiara Ganassino, DM         
U.O.C Pneumologia ad Indirizzo Oncologico -AORN Ospedali dei Colli Monaldi-Cotugno-CTO Not yet recruiting
Napoli, Italy, 80131
Contact: Danilo Rocco, DM       clinicaltrialsrocco@gmail.com   
Principal Investigator: Danilo Rocco, DM         
UOC di Oncologia Medica 2 - IOV Istituto Oncologico Veneto Not yet recruiting
Padova, Italy, 35128
Contact: Giulia Pasello, DM    0498215931    giulia.pasello@ioveneto.it   
Contact: Raffaella Verrienti    0498215608    raffaella.verrienti@ioveneto.it   
Principal Investigator: Giulia Pasello, DM         
UOC di Oncologia Medica- Azienda Ospidaliero Universitaria di Parma Not yet recruiting
Parma, Italy, 43126
Contact: Marcello Tiseo, DM    052170266061    mtiseo@ao.pr.it   
Contact: Roberta Camisa    052170266061    rcamisa@ao.pr.it   
Principal Investigator: Marcello Tiseo, DM         
US di Oncologia Medica - A.O. di Perugia Not yet recruiting
Perugia, Italy, 06132
Contact: Fausto Roila, DM    0755784099    roila.fausto@libero.it   
Principal Investigator: Fausto Roila, DM         
UO Pneumologia - A.O.U Pisana Not yet recruiting
Pisa, Italy, 56126
Contact: Antonio Chella, DM    +3950996653    anto.kell@tiscali.it   
Principal Investigator: Antonio Chella, DM         
S.C. di Oncologia Medica - IFO - Istituto Regina Elena Not yet recruiting
Roma, Italy, 00144
Contact: Sabrina Vari, DM    +39-06-52662752    sabrina.vari@ifo.gov.it   
Contact: Sonia Borrelli    +39-06-52662752    sonia.borrelli@ifo.gov.it   
Principal Investigator: Sabrina Vari, DM         
UOC di Oncologia Medica - Azienda Sanitaria Universitaria Integrata di Udine Not yet recruiting
Udine, Italy, 33100
Contact: Ciro Rossetto, dm    +39432559330    cirorossetto@asuiud.sanita.fvg.it   
Principal Investigator: Ciro Rossetto, DM         
Sponsors and Collaborators
University of Bologna
AOU S.Orsola Malpighi-Unit of Oncologic Molecular and Transplantations Pathology
Bioikos Ambiente Srl
Ipsen
Mipharm SpA
Additional Information:
Publications of Results:

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Responsible Party: Andrea Ardizzoni, Professor/MD, University of Bologna
ClinicalTrials.gov Identifier: NCT04131543    
Other Study ID Numbers: CRETA
First Posted: October 18, 2019    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms