Non Small Cell Lung Cancer
Conditions
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
Interventions
DRUGCabozantinib 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.
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 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.
Sponsors
AOU S.Orsola Malpighi-Unit of Oncologic Molecular and Transplantations Pathology
Bioikos Ambiente Srl
Ipsen
Mipharm SpA
University of Bologna
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, ope label clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (RR) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | PFS will be calculated from the first treatment intake to the date of progressive disease, or death. |
| 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 | OS will be calculated from the first treatment intake to death from any cause. |
| 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 | DOR will be calculated from the first treatment intake to the date of disease progression or death. |
| 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 | DCR will be measured as the sum of complete and partial responses + stable disease. |
Other
| Measure | Time frame | Description |
|---|---|---|
| RET aberration | 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) |
| RET-rearrangment on tumor tissue | 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. |
Countries
Italy
Outcome results
None listed