Nonsmall Cell Lung Cancer Stage III
Conditions
Brief summary
This is a multicenter, phase 2 non-randomized study to investigate the clinical feasibility and therapeutic efficacy of employing a MDT-based strategy in unresectable stage III ALK positive NSCLC following neoadjuvant alectinib in combination with platinum-based chemotherapy. Participants in this study must not have received any previous systemic anticancer therapy before enrollment. The study will consist of a 42-day screening period, a neoadjuvant treatment period, a local radical treatment period, a post-local treatment period, a safety follow-up visit occurring 28 days after the final dose of alectinib, and a survival follow-up period. In the neoadjuvant treatment period, participants will be provided with alectinib (600mg PO BID for 3 cycles) plus platinum-based chemotherapy for a maximum of 3 cycles (each cycle is 21 days). Following the completion of neoadjuvant therapy, all participants who are reassessed by MDT to be resectable after neoadjuvant treatment and have adequate lung functions would be provided with definite surgery. Otherwise, patients would be provided with radical radiotherapy through MDT discussion. For the surgery cohort, participants meet both the R0 resection, the pathological assessment criteria of pCR and have two consecutive landmark ctDNA tests that are negative will receive surveillance after surgery. Participants who do not meet all the above conditions will receive alectinib after surgery, adjuvant treatment should be initiated ideally 4-12 weeks after surgery, or according to local standard of care, treatment will continue until completion of treatment period (24 months), disease recurrence, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first. For the radical radiotherapy cohort, participants will receive alectinib after radiotherapy, adjuvant treatment should be initiated ideally 4-12 weeks after surgery, or according to local standard of care, the treatment will continue until completion of treatment period (24 months), disease progression, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first.
Interventions
DRUGAfter neoadjuvant alpelisib combined with chemotherapy, a multidisciplinary decision was made
For patients who have undergone three treatment cycles of neoadjuvant alaftinib combined with chemotherapy and have been evaluated by MDT as being resectable with good lung function, definitive surgery can be performed. Otherwise, the MDT will discuss with the patient to provide radical radiotherapy as the treatment option.
Sponsors
Wen-zhao ZHONG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply: * Signed Informed Consent Form * Age ≥ 18 years at time of signing Informed Consent Form * Ability to comply with the study protocol * Eligible to receive a platinum-based chemotherapy according to local labels or guidelines * Cytologically and/or histologically documented locally advanced, unresectable Stage III NSCLC * Staging should be based on Version 8 of the American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system. * Participants with T4 primary NSCLC with a separate nodule in a different ipsilateral lobe are not eligible. * Documented ALK fusion positivity by an eligible result from: ○ Previously obtained local test results as ordered by a healthcare provider from a high-quality and appropriately validated ALK fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments Certified or equivalent laboratory. Acceptable local test methods include the following * Next-generation sequencing; immunohistochemistry; fluorescence in situ hybridization; reverse transcription-polymerase chain reaction; NanoString. * Only National Medical Products Administration (NMPA)-approved tests for ALK fusions are acceptable. * Identification of a specific gene fusion partner is required (exceptions: ALK immunohistochemistry and certain PCR tests for which the gene fusion partner is not pre-specified as part of the test design). The use of positional 5/3 imbalance probe gene expression is not acceptable. * Eastern Cooperative Oncology Group Performance Status of 0, or 1 * Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study drug (i.e., Day 1 of Cycle 1): * ANC ≥1.5 \* 109/L (≥1500/L), without granulocyte colony-stimulating factor support * Platelet count ≥100\* 109/L ( 100,000/L), without the need for transfusion * Hemoglobin ≥ 90 g/L (≥9.0 g/dL) * Participants may be transfused or receive erythropoietic treatment as per local SOC to meet this criterion. * AST, ALT, and ALP ≤ 2.5 \*upper limit of normal (ULN) * Bilirubin≤1.5\*ULN with the following exception: Participants with known Gilbert disease: bilirubin level ≤ 3\* ULN * Creatinine clearance (CrCl) ≥ 60 mL/min, calculated using the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of CrCl * Albumin ≥ 25 g/L (≥ 2.5 g/dL) * For participants not receiving therapeutic anticoagulation: INR and aPTT≤1.5 \* ULN * For participants receiving therapeutic anticoagulation: stable anticoagulant regimen * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, as defined below: * Women must remain abstinent or use contraceptive methods with a failure rate of \<1% per year during the treatment period and for at least 90 days after the final dose of alectinib. While additionally adhering to the local label for alectinib and chemotherapy. Women must refrain from donating eggs during this same period. * A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). * Examples of contraceptive methods with a failure rate of\<1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The use of oral contraceptives should be supplemented with a barrier method (preferably a male condom). * The reliability of sexual abstinence should be evaluated in relation to the duration of the cohort and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not adequate methods of contraception. * Women should seek advice on fertility preservation before treatment with pemetrexed, cisplatin and carboplatin * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as defined below: * With a female partner of childbearing potential who is not pregnant, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of 1% per year during the treatment period and for at least 90 days after the final dose of alectinib. Men must refrain from donating sperm during this same period. * With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 90 days after the last final dose of alectinib to avoid exposing the embryo. The reliability of sexual abstinence should be evaluated in relation to the duration of the cohort and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not adequate methods of preventing drug exposure. * Men should seek advice on fertility preservation before treatment with pemetrexed, cisplatin, and carboplatin.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: * Any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-month EFS rate | From enrollment to the end of treatment at about 120 weeks(Preoperative treatment lasted for 9 weeks, MDT + surgery was assumed for 2 weeks, and continuous treatment began within 12 weeks after surgery and lasted for approximately 96 weeks.) | EFS is defined as the time frame from initiation of study treatment to any of the following events: progression of disease, recurrence disease, the occurrence of a new primary NSCLC or death due to any cause. Progression / recurrence will be assessed per RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Efficacy Objectives-Surgical rate | From enrollment to the end of treatment at 10 weeks（Each cycle lasts for 3 weeks, and there are a total of 3 cycles，and MDT assessment need 1 week）. | defined as the proportion of participants who underwent curative-intent surgical resection (R0) following the completion of neoadjuvant treatment. |
| Secondary Efficacy Objectives-ORR to neoadjuvant | From enrollment to the end of treatment at 10 weeks（Each cycle lasts for 3 weeks, and there are a total of 3 cycles，and MDT assessment need 1 week）. | defined as the percentage of participants who attain a CR or PR in the neoadjuvant stage, as determined by investigators according to RECIST v1.1. |
| Secondary Efficacy Objectives-EFS | From enrollment to the end of treatment at about 120 weeks(Preoperative treatment lasted for 9 weeks, MDT + surgery was assumed for 2 weeks, and continuous treatment began within 12 weeks after surgery and lasted for approximately 96 weeks.) | defined as time from initiation of study treatment to any of the following events: progression of disease, recurrence disease, the occurrence of a new primary NSCLC or death due to any cause. Progression/recurrence will be assessed per RECIST 1.1. |
| Secondary Efficacy Objectives-MPR rate | From enrollment to the end of treatment at 10 weeks（Each cycle lasts for 3 weeks, and there are a total of 3 cycles，and MDT assessment need 1 week）. | defined as the number of participants with \<10% residual tumor cells in primary lung cancer as evaluated by thoracic pathologists, divided by the number of all participants who underwent surgery. |
| Secondary Efficacy Objectives-pCR rate | From enrollment to the end of treatment at 10 weeks（Each cycle lasts for 3 weeks, and there are a total of 3 cycles，and MDT assessment need 1 week）. | defined as number of participants with no residual tumor cells in both primary lung cancer and draining lymph nodes as evaluated by the thoracic pathologist, divided by the number of all participants who underwent surgery. |
| Secondary Efficacy Objectives-OS | From enrollment to the end of treatment at about 120 weeks(Preoperative treatment lasted for 9 weeks, MDT + surgery was assumed for 2 weeks, and continuous treatment began within 12 weeks after surgery and lasted for approximately 96 weeks.) | defined as the time from initiation of study treatment to death from any cause |
Contacts
CONTACTWEN ZHAO ZHONG, MD
Outcome results
None listed