Recurrent or metastatic endometrial, ovarian, fallopian tube, primary peritoneal, or cervical carcinoma. MedDRA version: 21.1 Level: PT Classification code 10014734 Term: Endometrial cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10014736 Term: Endometrial cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) Med
Conditions
Interventions
Product Name: Anlotinib Hydrochloride
Product Code: AL3818
Pharmaceutical Form: Capsule
INN or Proposed INN: Catequentinib
CAS Number: 1058156-90-3
Current Sponsor code: AL3818
Concentration unit: mg
Sponsors
ADVENCHEN LABORATORIES, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for this study: 1. Female = 18 years of age 2. Histologically proven diagnosis of: a. Endometrial and other uterine cancers with tumors of all histologies i. Recurrent Stage I to II endometrial and other uterine cancers, after at least one prior line of standard therapy, requiring further treatment with platinumbased chemotherapy ii. Advanced Stage III to IV endometrial and other uterine cancers requiring treatment with platinum-based chemotherapy b. Ovarian Cancer: Platinum-sensitive or platinum-resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer treated with at least one prior line of platinum-based chemotherapy and requiring further treatment. (Part 1/Phase Ib, Part 2/Phase 2a) Platinum-sensitive is defined as cancer progression = 6 months after platinum-based chemotherapy. Platinum-resistant is defined as cancer progression 1.5 x ULN, creatinine clearance must be > 50 mL/min. c. Hepatic function: bilirubin = 1.5 x ULN or = 3.0 x ULN for subjects with Gilbert Syndrome; AST and ALT = 3.0 × ULN. d. Coagulation profile: international normalized ratio (INR) is = 1.5 and an aPTT or PTT < 1.2 x ULN. e. ECOG performance = 2 7. Women of child-bearing potential must agree to use contraceptive measures starting 1 week before C1D1 until 4 weeks after the last dose of study treatment and have a negative serum pregnancy tes
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the study: 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 C1D1 (a major surgical procedure is defined as requiring general anesthesia). 3. (Intentionally left blank) 4. Active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels. 5. History or evidence upon physical examination of central nervous system (CNS) disease including primary brain tumor; seizures not controlled with standard medical therapy; and history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within 6 months of enrollment. a. Subjects with metastatic CNS tumors may participate in this study if the subject is > 28 days from therapy completion (including radiation and/or surgery), is clinically stable at the time of study enrollment, and is not receiving corticosteroid therapy. 6. Proteinuria on urinalysis within 28 days of enrollment. Subjects discovered to have a urine protein of 1+ on dipstick or = 30 mg/dl at baseline should undergo a 24-hour urine collection and demonstrate < 1000 mg protein per 24 hours or spot urine protein (mg/dL) to creatinine (mg/dL) ratio must be <1.0 to allow participation in the study. 7. 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 (Appendix E); serious cardiac arrhythmia requiring medication; and Grade II or greater peripheral vascular disease. 8. Women who are pregnant or nursing. 9. (Intentionally left blank) 10. Clinically significant, uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia. 11. Hemoptysis within 3 months prior to enrollment. 12. Acute or chronic liver disease, active hepatitis A or B with known cirrhosis or liver dysfunction. 13. Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 28 days (42 days in cases of mitomycin C, nitrosourea, lomustine) prior to enrollment. 14. 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 lifethreatening medical condition that required it. 15. Known history of human immunodeficiency virus infection (HIV). 16. Active bacterial infections requiring systemic antibiotics (excluding uncomplicated urinary tract infection). 17. Other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years prior to enrollment or whose previous cancer treatment contraindicates this protocol therapy. 18. History of non-malignant gastrointestinal bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months prior to enrollment that in the opinion of the investigator may place the subject at risk of side effects on an anti-angiogenesis product. 19. History of significant vascular disease (e.g. aortic aneurysm, aortic dissection). 20. Intra-abdominal abscess within the last 3 months of enrollment. 21. Pre-existing uncontrolled hypertension as documented by two baseline blood pressure readings taken at least five minutes apart, defined as systol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase Ib/Part 1 – Completed ? To determine the RP2D for part 2 of adding oral AL3818 to standard platinum-based chemotherapy with carboplatin (or cisplatin) and paclitaxel in subjects with recurrent or metastatic endometrial or other uterine, ovarian, fallopian, primary peritoneal or cervical cancer via evaluation of DLT events. Phase IIa/Part 2 Objectives ? To measure objective response rates (ORR) in subjects with recurrent or metastatic endometrial or other uterine, ovarian, fallopian, primary peritoneal or cervical cancer treated with AL3818 in combination with platinum-based chemotherapy or other standard chemotherapies. Phase III/Part 3 Objectives (ALIFTUS) ? To evaluate the efficacy between the Active Arm (AL3818 in combination with background chemotherapy) and Control Arm (background chemotherapy alone arm) as measured by the primary endpoint of Progression Free Survival (PFS). PFS will be evaluated by a blinded independent radiological review (BICR).;Secondary Objective: Phase Ib/Part 1 (Completed): To investigate the safety and tolerability of adding oral AL3818 to standard platinum-based chemotherapy with carboplatin (or cisplatin) and paclitaxel. Phase IIa/Part 2: ? To measure CBR, PFS and OS in subjects with recurrent or metastatic endometrial or other uterine, ovarian, fallopian, primary peritoneal or cervical cancer treated with AL3818 in combination with platinum-based chemotherapy or other standard chemotherapies. ? To obtain data on safety and tolerability in subjects with recurrent or metastatic endometrial or other uterine, ovarian, fallopian, primary peritoneal or cervical cancer treated with AL3818 in combination with platinum-based chemotherapy or other standard chemotherapies. Phase III/Part 3 Objectives (ALIFTUS): To evaluate the efficacy between the Active Arm and Control Arm as measured by the secondary endpoints of ORR, DOR and OS. ORR will be evaluated by a blinded independent radiological review.;Primary end point | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase Ib/Part 1 (Completed): To investigate the safety and tolerability of adding oral AL3818 to standard platinum-based chemotherapy with carboplatin (or cisplatin) and paclitaxel. Phase IIa/Part 2 1. Clinical Benefit Rate (CBR) is defined as the proportion of subjects who achieve a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) as best responses according to RECIST 1.1. 2. Progression-Free Survival (PFS) is defined as the median number of months from the date of C1D1 until the first documented sign of disease progression or death due to any causes, whichever occurs earlier. 3. Overall Survival (OS) is defined as the time from C1D1 until death from any cause. Phase III/Part 3 Objectives (ALIFTUS): To evaluate the efficacy between the Active Arm and Control Arm as measured by the secondary endpoints of ORR, DOR and OS. ORR will be evaluated by a blinded independent radiological review.;Timepoint(s) of evaluation of this end point: Phase Ib/Part 1: C1D1 to EoT Phase IIa/Part 2: Baseline/screening, C4D1, C8D1, C10D1, C12D1, C16D1, C20D1, C24D1 Phase III/Part 3: Baseline/screening, C3D1, C5D1, C8D1, C11D1, C15D1, C19D1, C24D1 OS: from C1D1 until death from any cause. | — |
Countries
Spain, United States
Outcome results
None listed