Study With Afuresertib and Paclitaxel in Platinum Resistant Ovarian

NCT04374630 | Completed Phase 2 FDA Drug

• 1 other identifier: LAE002INT2001
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 47

Brief Summary

Afuresertib is an AKT inhibitor, a new class of agents under development that may provide physicians with a new clinical option to control platinum resistant ovarian cancer (PROC) progression. Afuresertib plus chemotherapy has demonstrated anti-tumor efficacy and an acceptable safety profile in patients with PROC in a published Phase I/II study. Therefore, the combination of afuresertib plus weekly paclitaxel could represent a clinically meaningful step forward in the clinical management of these difficult-to-treat patients with PROC.

Conditions

Platinum-resistant Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  Radiographic imaging will be performed and assessed by investigators

  Change from Baseline every 6 weeks × 30 weeks, then every 8 weeks through study completion, an average of 1 year

Secondary Outcomes (23)

• Overall survival (OS)

  From date of randomization until date of death, from any cause, assessed up to 1 year.

• Objective response rate (ORR) according to RECIST 1.1

  Change from Baseline every 6 weeks × 30 weeks, then every 8 weeks through study completion, an average 1 year.

• Duration of response (DOR) according to RECIST 1.1

  Change from Baseline every 6 weeks × 30 weeks, then every 8 weeks through study completion, an average of 1 year.

• Disease control rate (DCR) according to RECIST 1.1

  Change from Baseline every 6 weeks × 30 weeks, then every 8 weeks through study completion, an average of 1 year.

• Best overall response (BOR) according to RECIST 1.1

  Change form Baseline every 6 weeks × 30 weeks, then every 8 weeks through study completion, an average of 1 year.

Other Outcomes (7)

• PFS based on RECIST 1.1

  After C2 (each cycle is 21 days), then every 6 weeks for 30 weeks, then every 8 weeks through study completion, an average up to 1 year.

• OS

  From date of randomization until date of death

• ORR based on RECIST 1.1

  After C2 (each cycle is 21 days), every 6 weeks x 30 weeks, then every 8 weeks through study completion, an avergae of 1 year.

Study Arms (2)

Arm 1

EXPERIMENTAL

Arm 1 is afuresertib 125 mg PO QD + paclitaxel 80 mg/m2 intravenous (IV) infusion over 1 hour on Days 1, 8 and 15 of a 3 week cycle.

Drug: Paclitaxel; Drug: Afuresertib

Arm 2

ACTIVE COMPARATOR

Arm 2 is paclitaxel 80 mg/m2 IV infusion over 1 hour on Days 1, 8, and 15 of a 3 week cycle

Drug: Paclitaxel

Interventions

Paclitaxel DRUG

Commercially available paclitaxel for IV administration will be obtained by clinical sites in US.

Arm 1; Arm 2

Afuresertib DRUG

Each afuresertib 50 mg tablet, intended for oral administration, contains afuresertib (hydrochloride salt) equivalent to 50 mg of afuresertib (free base). Each afuresertib 75 mg tablet, intended for oral administration, contains afuresertib (hydrochloride salt) equivalent to 75 mg of afuresertib (free base)

Also known as: LAE002

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Female patients at least 18 years of age at the time of signing the informed consent form and capable of giving written informed consent, which includes willingness to comply with the requirements and restrictions listed in the consent form.
• Must provide informed consent for the procedures and the tests for PI3K/AKT/PTEN pathway alterations, BRCA1/2 mutations, and/or level of phospho-AKT. The archival tumor biopsy sample collected less than 1 year is preferred. If no archival tumor sample is available, fresh biopsy will be recommended. For patients who cannot provide a tumor sample or cannot accept fresh tumor biopsy, the Sponsor should be consulted about their qualification to enter this study.
• Patients must have histologically or cytologically confirmed high grade serous OC, endometroid OC, or ovarian clear cell carcinoma (including fallopian tube and primary peritoneal cancers). Carcinosarcoma, sarcoma, mucinous OC, or low-grade serous OC or the other histologies must be excluded.
• Must not have previously received prior AKT or PI3K pathway or mTOR inhibitors.
• Must have PROC (including fallopian tube and primary peritoneal carcinoma), defined as disease relapsed between 1 to 6 months after the last dose of the first-line platinum-based therapy (at least 3 cycles), or progressed during or relapsed within 6 months of the last dose of platinum-based 2nd-5th line therapies.
• The OC patients must have received 1 to 5 prior chemotherapies including no more than one chemotherapy after PROC was diagnosed. Combination therapy with two or more drugs will be considered as one therapy, whereas maintenance therapy will be considered as continuation of the previous systemic treatment.
• Patients should be appropriate candidates for treatment with single agent weekly paclitaxel based on investigator's clinical assessment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Must meet the following criteria for hematology parameters:
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelets ≥ 100,000/µL
• Hemoglobin ≥ 9.0 g/dL
• Total serum bilirubin ≤ 1.5 × upper limit of normal (ULN) (in patients with known Gilbert's syndrome, total bilirubin ≤ 3 × ULN with direct bilirubin ≤ 1.5 × ULN).
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) must be \< 2.5 × institutional ULN. For patients with liver metastasis, AST/ALT must be \< 5.0 × institutional ULN.
• Creatinine within 1.5 × ULN or creatinine clearance \> 30 mL/min by Cockcroft Gault formula (Appendix 1).

You may not qualify if:

• \. Primary platinum refractory disease, defined as "disease progression during or relapsed within 1 month after the last dose of the first-line platinum based therapy".
• Known or suspected brain metastases.
• Receiving any other anticancer therapeutic agents other than study medicines.
• Uncontrolled ascites.
• Known symptomatic or impending cord compression, except if the patient has received definitive treatment for this and demonstrates evidence of clinically stable disease.
• Presence of other active cancer within 3 years prior to enrollment (other than basal cell or squamous cell skin cancer, or any other cancer in situ currently in complete remission).
• History of seizure or condition that may predispose to seizure that needs anti-epileptic medications; brain arteriovenous malformation; or intracranial masses, such as schwannomas and meningiomas that are causing edema or mass effect.
• Known allergies, hypersensitivity, or intolerance to the excipients of afuresertib (for excipient information, refer to the IB17).
• Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (eg, compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Any medical contraindication to the use of paclitaxel.
• Prior radiotherapy ≤ 15 days prior to Study Day 1, with the exception of a single fraction of radiotherapy for the purposes of palliation, which is permitted.
• History of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or torsade de pointes).
• Prolonged corrected QT interval by the Fridericia's correction formula (QTcF) on the screening ECG \> 470 msec. Receiving concomitant medications known to prolong QTc, or which are associated with torsade de pointes, and are unable to discontinue use while receiving study drug.
• History or evidence for any of the following: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks) within 6 months prior to Study Day 1 or New York Heart Association Class III to IV heart disease.
• Presence of uncontrolled hypertension (systolic blood pressure \[BP\] \> 160 mmHg or diastolic BP \> 100 mmHg). Patients with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment.

Sponsors & Collaborators

• Laekna Limited: lead

Study Sites (47)

Arizona Oncology Associates

Phoenix, Arizona, 85016, United States

Location

Arizona Oncology

Tucson, Arizona, 85711, United States

Location

Highlands Oncology Group

Rogers, Arkansas, 72758, United States

Location

Gynecology Oncology Associates Newport Beach

Newport Beach, California, 92663, United States

Location

Rocky Mountain Cancer Centers

Littleton, Colorado, 80120, United States

Location

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Women's Cancer Care

Covington, Louisiana, 70433, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01605, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

MD Anderson Cancer Center at Cooper

Camden, New Jersey, 08103, United States

Location

Holy Name Medical Center

Teaneck, New Jersey, 07666, United States

Location

Southwest Women's Oncology Group

Albuquerque, New Mexico, 87106, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

OHCare Oncology Hematology Care (OHC), Inc. - Kenwood Office

Cincinnati, Ohio, 45242, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Abington Memorial Hospital

Willow Grove, Pennsylvania, 19090, United States

Location

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

Texas Oncology

Austin, Texas, 78731, United States

Location

Texas Oncology

Fort Worth, Texas, 76104, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

USO Texas Oncology

Longview, Texas, 75601, United States

Location

US Texas Oncology

San Antonio, Texas, 78240, United States

Location

Baylor Scott & White Medical Center

Temple, Texas, 76508, United States

Location

Texas Oncology

The Woodlands, Texas, 77380, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

University of Washington/Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Beijing Obstetrics & Gynecology Hospital, Capital Medical University

Beijing, China

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

Location

Peking University Cancer Hospital

Beijing, China

Location

Chongqing University Cancer Hospital

Chongqing, China

Location

Sun Yat-sen University Cancer Center

Guangdong, China

Location

Harbin Medical University Cancer Hospital

Heilongjiang, China

Location

Henan Cancer Hospital

Henan, China

Location

Hubei Cancer Hospital

Hubei, China

Location

Hunan Cancer Hospital

Hunan, China

Location

Jilin Cancer Hospital

Jilin, China

Location

Liaoning Cancer Hospital

Liaoyang, China

Location

Qilu Hospital of Shandong University

Shandong, China

Location

Obstetrics & Gynecology Hospital of Fudan University

Shanghai, China

Location

Zhongshan Hospital affiliated to Fudan University

Shanghai, China

Location

West China Second University Hospital,Sichuan University

Sichuan, China

Location

The Second Hospital of Tianjin Medical University

Tianjin, China

Location

Women's Hospital school of medicine Zhejiang University

Zhejiang, China

Location

MeSH Terms

Interventions

Paclitaxel; afuresertib

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Herzog Thomas, Professor

  University of Cincinnati Medical Center/USA/1010

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: May 5, 2020
• Study Start: June 9, 2020
• Primary Completion: July 31, 2023
• Study Completion: June 28, 2024
• Last Updated: September 10, 2025

Record last verified: 2025-03

Locations

CN (17); US (30)