Non-Small Cell Lung, Renal Cell Carcinoma (RCC), Small Cell Lung Cancer
Conditions
Keywords
Recurrent small cell lung caner, Advanced small cell lung cancer, Metastatic Small lung cancer, ≥2nd Line treatment, Non small cell lung cancer, Renal Cell Carcinoma
Brief summary
This trial is a Phase II trial designed to evaluate the safety and efficacy of using oral AL8326 , a multi-targeted receptor Tyrosine Kinase Inhibitor( TKI) , to recurrent, advanced, or metastatic small cell lung cancer (SCLC) patients , Non-Small Cell Lung (NSCLC) and Renal Cell Carcinoma patients who need ≥2nd line treatment .
Detailed description
This study is designed for two steps: Phase 2 Optimal Biological Dose (OBD) finding and Phase 2 expansion cohort study after OBD determination. The Phase 2 study aims to find optimal biological dose (OBD) initially. Patients will be randomized to 3 different dosing groups in OBD finding cohorts. Each cohort will enroll 6-12 SCLC patients who need ≥2nd line treatment without or with brain metastasis which is controlled with no active hemorrhage. This OBD finding cohort will also evaluate the pharmacokinetic profile of AL8326. OBD patient enrollment of 40 mg (n=12) and 60 mg (N=12) have been completed, waiting data maturing, 80 mg (n=4) has been stopped due to high intolerability. 40mg and 60mg cohort group can be expanded to an additional 6-12 patients in each cohort with only sparse PK sampling requirement if OBD is not able to be determined in early 12 patients of each cohort. Non-Small Cell Lung (NSCLC) and Renal Cell Carcinoma (RCC) are added to this protocol as additional expansion cohorts.
Interventions
DRUGAL8326 40 mg
Taken AL3826 at 40mg QD orally
DRUGAL8326 60 mg
Taken AL3826 at 60mg QD orally
DRUGAL8326 80 mg--stopped
Taken AL3826 at 80 mg QD orally
Sponsors
Advenchen Pharmaceuticals, LLC.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The phase 2 study aims to find optimal biological dose (OBD) for Phase 2 expansion cohort clinical study. Patients will be randomized to a 3 different dosing daily AL8326 groups ( low. middle. high) in 1:1:1 ratio in OBD finding cohorts. ----OBD patient enrollment of 40 mg (n=12) and 60 mg (N=12) have been completed, waiting data maturing, 80 mg (n=4) has been stopped due to high intolerability. A phase 2 expansion cohort will enroll SCLC--on hold NSCLC -≥2nd line treatment with up to n=15 patients in 40 mg RCC-≥2nd line treatment with up to n=15 patients in 60 mg
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: 1. Male or female, 18 years of age or older 2. ECOG performance status of 0 or 1 3. Histologically or cytologically confirmed SCLC /NSCLC/RCC 4. Have at least 1 lesion that meets the criteria for being measurable, as defined by RECIST 1.1 5. Have a life expectancy of at least 3 months Major
Exclusion criteria
1. Serious, non-healing wound, ulcer or bone fracture 2. Major surgical procedure within 28 days or minor surgical procedure performed within 7 days prior to treatment 3. Active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels 4. Clinically significant cardiovascular disease including uncontrolled hypertension; myocardial infarction or unstable angina within 6 months prior to enrollment; New York Heart Association (NYHA) Grade II or greater congestive heart failure serious cardiac arrhythmia requiring medication; and Grade II or greater peripheral vascular disease 5. Hemoptysis within 3 months prior to enrollment 6. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there is an emergent or life-threatening medical condition that required it. More information available upon request
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Optimal biological dose ( OBD ) | 12 months | Determine the Optimal biological dose ( OBD ) via evaluation of dose limiting toxicity (DLT) events to decide the dosing using in expanded cohort |
| Objective Response Rates (ORR) | 12 month | Evaluate the efficacy among 3 different dosing groups |
| ORR evaluation for NSCLC and RCC | 24 month | ORR evaluation for NSCLC and RCC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response ( DOR) | 36 month | DOR for SCLC OBD group plus expansion cohort, NSCLC and RCC cohortgroup; |
| Progression-Free Survival (PFS) | 36 month | PFS for SCLC OBD group plus expansion cohort, NSCLC and RCC cohortgroup |
| Pharmacokinetic endpoints | 24 month | Pharmacokinetic endpoints Maximum Plasma Concentration ( Cmax) |
| Pharmacokinetic endpoint Area Under the Curve (AUC) | 24 month | — |
Countries
Spain, United States
Contacts
CONTACTShiying Sprinzl
CONTACTJudy Chen
PRINCIPAL_INVESTIGATORSaiama Waqar, MD
Washington University School of Medicine
Outcome results
None listed