Lung cancer lung tumor
Conditions
Interventions
None listed
Sponsors
Millenium Pharmaceuticals
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged *18 years. 2. Histologically or cytologically confirmed locally advanced NSCLC in which the patient is not a candidate for definitive therapy; or, the patient has recurrent or metastatic (Stage IV) disease. 3. Refractory or intolerant to standard available therapies. 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. 5. Minimum life expectancy of 3 months or more. 6. Adequate organ function as defined by the protocol criteria. a) Total serum bilirubin *1.5 × upper limit of normal (ULN) (*3 × ULN for patients with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy); b) Alanine aminotransferase and aspartate aminotransferase *2.5 × ULN (or *5 × ULN if liver function abnormalities are due to underlying malignancy); c) Estimated creatinine clearance *30 mL/min (calculated by using the Cockcroft-Gault equation); d) Serum albumin *2 g/dL; e) Serum lipase *1.5 × ULN; and f) Serum amylase *1.5 × ULN unless the increased serum amylase is due to salivary isoenzymes. 7. Adequate bone marrow function, as defined by the protocol criteria. a) Absolute neutrophil count *1.5 × 109/L; b) Platelet count *75 × 109/L; and c) Hemoglobin *9.0 g/dL. 8. Normal QT interval on screening ECG, defined as QTcF of *450 msec in males or *470 msec in females. (as conducted and interpreted in accordance to local institutional practices and confirmed by PI). 9. All toxicities from prior anticancer therapy must have resolved to *Grade 1 according to the NCI CTCAE version 5.0 [1], or have resolved to baseline, at the time of first dose of TAK-788. Note: treatment-related Grade 2 or 3 alopecia and treatment-related Grade 2 peripheral neuropathy are allowed if deemed irreversible. 10. Female patients who are of childbearing potential, agree to comply with protocol-defined contraception criteria or practice true abstinence. 11. Male patients agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, or agree to practice true abstinence. 12. If female, a negative serum or urine pregnancy test result during the screening period. 13. Suitable venous access for study-required blood sampling (ie, including for PK, pharmacodynamics, and clinical laboratory tests). 14. Willingness and ability to comply with scheduled visits and study procedures. 15. Signed and dated the informed consent indicating that the patient has been informed of all pertinent aspects of the study. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
Exclusion criteria
Exclusion criteria: 1. Previously received TAK-788. 2. Received a strong or moderate CYP3A inhibitor or strong or moderate CYP3A inducer within 2 weeks prior to the first dose of TAK-788. 3. Received small-molecule anticancer therapy (including but not limited to cytotoxic chemotherapy and investigational agents) within 2 weeks prior to the first dose of TAK-788. 4. Received antineoplastic monoclonal antibodies including check point inhibitors within 28 days of the first dose of TAK-788. 5. Received radiotherapy *14 days prior to the first dose of TAK-788. However, patients are allowed to receive any of the following treatments up to 7 days prior to the first dose: (a) Stereotactic radiosurgery (SRS), (b) stereotactic body radiation therapy (SBRT), or (c) palliative radiation outside the chest and brain. 6. Major surgery within 28 days prior to the first dose of TAK-788. Minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed. 7. Diagnosed with another primary malignancy other than NSCLC except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or another primary malignancy and is definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy. 8. Have known active brain metastases (have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions). Brain metastases are allowed if they have been treated with surgery and/or radiation and have been stable without requiring corticosteroids to control symptoms within 7 days before the first dose of TAK-788, and have no evidence of new or enlarging brain metastases. 9. Current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic). 10. Have uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure. 11. Significant, uncontrolled, or active cardiovascular disease. 12. Treatment with medications known to be associated with the development of torsades de pointes. 13. Current or history of interstitial lung disease, radiation pneumonitis that required steroid treatment, or drugrelated pneumonitis. 14. Ongoing or active infection including, but not limited to, the requirement for IV antibiotics, or a known history of human immunodeficiency virus infection. Testing is not required in the absence of history. Patients who are positive for hepatitis B surface antigen or anti-hepatitis C virus antibody may be eligible (see full protocol for further details). 15. Gastrointestinal illness or disorder that could affect oral absorption of TAK-788 or midazolam. 16. If female, the patient is lactating and breastfeeding. Female patients who are lactating will be eligible if they discontinue breastfeeding. 17. History of, or suspected, hypersensitivity or allergy to midazolam or its excipients or TAK-788. 18. Any condition or illness that, in the opinion of the investigator, might compromise patient safety or interfere with the evaluation of the safety of the study drug. 19. Admission or evidence of illicit drug use, drug abuse,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Criteria for Evaluation and Analyses: The primary endpoints of the study include, but are not limited to the following midazolam PK parameters after oral or IV administration in the presence and absence of TAK-788: Primary Endpoints * The geometric mean ratios and 90% CI of Cmax and AUC* for midazolam administered orally with TAK-788 and when orally administered as midazolam alone. * The geometric mean ratios and 90% CI of Cmax and AUC* for midazolam administered intravenously with TAK-788 and when intravenously administered as midazolam alone | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints The secondary endpoints of the study encompass the safety profile of TAK-788 and are as follows: * AEs. * Clinical laboratory tests (hematology and clinical chemistry). * Vital signs. | — |
Countries
Netherlands
Outcome results
None listed