A Phase 3 Randomized Open-label Study of Brigatinib Versus Alectinib in Advanced ALK-positive Non–Small-Cell Lung Cancer Patients Who Have Progressed on Crizotinib
- Conditions
- ALK positive Locally Advanced or Metastatic Non-small Cell Lung CancerMedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001957-29-GR
- Lead Sponsor
- Takeda Development Center Americas, Inc. (TDCA)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 246
1. Male or female, patients aged 18 years or older or of local legal adult age.
2. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
3. Have histologically or cytologically confirmed stage IIIB (locally advanced or recurrent) or stage IV NSCLC.
4. Must meet one of the following criteria:
a) Have documentation of ALK rearrangement by a positive result from the Vysis ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit or the Ventana ALK (D5F3) CDx Assay or Foundation Medicine’s FoundationOne CDx.
b) Have documented ALK rearrangement by a different test and be able to provide tumor sample to the central laboratory. (Note: central laboratory ALK rearrangement testing results are not required to be obtained before randomization.)
5. Had PD while on crizotinib, as assessed by the investigator or treating physician. (Note: crizotinib does not need to be the last therapy a patient received. The patient may have received chemotherapy as his/her last therapy.)
6. Treatment with crizotinib for at least 4 weeks before progression.
7. Have had no other ALK inhibitor other than crizotinib.
8. Have had no more than 2 prior regimens of systemic anticancer therapy (other than crizotinib) in the locally advanced or metastatic setting*.
Note: a systemic anticancer therapy regimen will be counted if it is administered over for at least 1 complete cycle. A new anticancer agent used as maintenance therapy will be counted as a new regimen. Neoadjuvant or adjuvant systemic anticancer therapy will be counted as a prior regimen if disease progression/recurrence occurred within 12 months upon completion of this neoadjuvant or adjuvant therapy.
*Systemic therapy followed by maintenance therapy will be considered as one regimen if
the maintenance therapy consists of a drug or drugs that were used in the regimen that
immediately preceded maintenance.
9. Have at least 1 measurable (ie, target) lesion per RECIST v1.1.
10. Have recovered from toxicities related to prior anticancer therapy to NCI CTCAE v4.03 grade =1. (Note: treatment-related alopecia or peripheral neuropathy that are grade >1 are allowed, if deemed irreversible.)
11. Have adequate organ function, as determined by:
a) Total bilirubin =1.5 times the upper limit of normal (ULN).
b) Estimated glomerular filtration rate =30 mL/minute/1.73 m2, using the modification of diet in renal disease equation.
c) Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =2.5 × ULN; =5 × ULN is acceptable if liver metastases are present.
d) Serum lipase =1.5 × ULN.
e) Platelet count =75 ×109/L.
f) Hemoglobin =9 g/dL.
g) Absolute neutrophil count =1.5 × 109/L.
12. Suitable venous access for study-required blood sampling (ie, including PK and laboratory safety tests).
13. Have the willingness and ability to comply with scheduled visits and study procedures.
14. For female patients of childbearing potential, have a negative pregnancy test documented before randomization.
15. Female patients of childbearing potential and male patients with partners of childbearling potential must agree to use a highly effective nonhormonal form of contraception with their sexual partners during the dosing period and for a period of at least 120 days after the end of treatment with either brigatinib or alectinib.
16. Male patients, even if surgically sterilized (i.e., status postvasectomy), who:
a) Agree to practice effective barrier contraception during the entire study treatment period an
1. Participation in the control (crizotinib) arm of Study AP26113-13-301 (ALTA 1L).
2. Received crizotinib within 7 days before randomization.
3. Have a history or presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis.
4. Have uncontrolled hypertension. Patients with hypertension should be under treatment for control of blood pressure upon study entry.
5. Received systemic treatment with strong cytochrome P-450 (CYP) 3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, or moderate CYP3A inducers within 14 days before randomization.
6. Treatment with any investigational systemic anticancer agents within 14 days or 5 half-lives, whichever is longer, before randomization.
7.Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated nonmetastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
8. Received chemotherapy or radiation therapy within 14 days before randomization except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
9. Received anticancer monoclonal antibodies within 30 days of randomization.
10. Had major surgery within 30 days of randomization. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.
11. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening (patients with asymptomatic brain metastases or patients who have stable symptoms and did not require an increased dose of corticosteroids to control symptoms within 7 days before randomization will be enrolled). Note: If a patient has worsening neurological symptoms or signs due to CNS metastasis, the patient needs to complete local therapy and be neurologically stable (with no requirement for an increasing dose of corticosteroids or use of anticonvulsants) for at least 7 days before randomization.
12. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed.
13. Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to the following:
a) Myocardial infarction within 6 months before randomization.
b) Unstable angina within 6 months before randomization.
c) New York Heart Association Class III or IV heart failure within 6 months before randomization.
d) History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician.
e) Any history of clinically significant ventricular arrhythmia.
14. Had cerebrovascular accident or transient ischemic attack within 6 months before first dose of study drug.
15. Have malabsorption syndrome or other gastrointestinal illness or condition that could affect oral absorption of the study drug.
16. Have an ongoing or active infection, including but not limited to, the requirement for intravenous antibiotics.
17. Have a known history of HIV infection. Testing is not required in the absence of history.
18. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection. Testing is not required in the absence of history.
19. Any serious medical condition or psychiatric
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method