NCT02584478

Phase 1/2a/3 Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002)

A Phase 1/2a/3 Evaluation of the Safety and Efficacy of Adding AL3818 (Anlotinib, INN: Catequentinib), a Dual Receptor Tyrosine Kinase Inhibitor, to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 294 (actual)
• Sponsor: Advenchen Laboratories, LLC · Industry
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This trial is a Phase 1b/2a/3 trial designed to evaluate the safety and efficacy of adding oral AL3818 (Anlotinib, INN: Catequentinib), a Dual Receptor Tyrosine Kinase Inhibitor, to standard platinum-based chemotherapy concurrently in Subjects with Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma.

Detailed description

This trial is a Phase 1b/2a/3 trial designed to evaluate the safety and efficacy of adding oral AL3818(Anlotinib, INN: Catequentinib) to standard platinum-based chemotherapy concurrently and continued as a maintenance therapy for up to 12 months, in subjects with recurrent or metastatic endometrial, ovarian, fallopian, primary peritoneal, or cervical carcinoma. AL3818 is a novel small molecule dual receptor tyrosine kinase inhibitor, which shows highly selective inhibition of fibroblast growth factor receptor (FGFr) and vascular endothelial growth factor receptor (VEGFR). Preclinical studies of this agent in mouse models, including various cancer xenografts, have demonstrated that treatment of tumor-bearing mice with AL3818 induces tumor reductions. Phase 1 \& 2: This study is divided into two parts. The objective of Part 1 is the evaluation of the safety and tolerability of adding oral AL3818 to standard carboplatin plus paclitaxel chemotherapy for a cycle of 21 days to determine the recommended Phase II dose (RP2D). Phase 1 / Part 1 is now complete. Part 2-The objective of Part 2 is evaluation of preliminary efficacy and the safety of adding oral AL3818 at the RP2D determined in Part 1 to carboplatin and paclitaxel chemotherapy for 6 cycles. Continuous maintenance mono therapy with 14 days on and 7 days off regimen at the RP2D will be conducted up to 12 months and is extendable beyond until disease progression. Phase I is closed and Phase 2 is closed. Phase 3: This study is currently a Phase III, multi-center, randomized trial with active control designed to evaluate the efficacy and safety of AL3818 8 mg plus background treatment (Active Arm) vs background treatment alone (Control Arm), where three background treatments, weekly paclitaxel, pegylated liposomal doxorubicin (PLD), and topotecan are utilized. Oral AL3818 8 mg may be given concurrently with background treatment or alone if the background treatment must be discontinued due to its toxicity for up to 24 cycles of therapy, in subjects with recurrent or metastatic platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer. Phase 3 is open.

Conditions

• Endometrial Carcinoma
• Ovarian Carcinoma
• Fallopian Tube Carcinoma
• Primary Peritoneal Carcinoma
• Cervical Carcinoma

Interventions

Type	Name	Description
DRUG	AL3818	Taken daily from Day 8 to Day 21 (14 days),administered orally combination with one background chemotherapy in 21-day cycles.
DRUG	Paclitaxel	Weekly single agent Paclitaxel will be administered on Day 1, 8, and 15 of each 21-day cycle. Suggested dose: 80 mg/m\^2 intravenously or local standard. Paclitaxel may also be administered once weekly with a 1-week break every 3 weeks in lieu of every week
DRUG	Pegylated Liposomal Doxorubicin (PLD)	Single agent Pegylated Liposomal Doxorubicin (PLD) administered every 4 weeks on the following cycle days corresponding with AL3818 cycles until maximum cumulative dose per local standard reached. Suggested dose: 40 mg/m\^2 intravenously or local standard
DRUG	Topotecan	Daily Topotecan on Days 1-5 of each 21-day cycle Suggested dose: 1.25 mg/m2 intravenously or local standard OR Weekly Topotecan with a 1 week break every 3 weeks. Suggested dose: 4 mg/m2 intravenously or local standard
DRUG	Topotecan	Weekly Topotecan with a 1 week break every 3 weeks Suggested dose: 4 mg/m2 intravenously or local standard
DRUG	Carboplatin	AUC 5/6 on Day 1 of each 21-Day cycles
DRUG	Paclitaxel	175mg/m2 IV over 3 hours on Day 1 of each 21-Day cycle
DRUG	AL3818	Taken daily from Day 8 to Day 21 (14 days). Administered orally.

Timeline

• Start date: 2015-12-01
• Primary completion: 2024-10-01
• Completion: 2024-12-01
• First posted: 2015-10-22
• Last updated: 2023-11-08

Locations

41 sites across 6 countries: United States, China, Italy, South Korea, Spain, United Kingdom