Ovarian Cancer Clinical Trial

Study With Afuresertib and Paclitaxel in Platinum Resistant Ovarian

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.

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Full Description

A total of approximately 141 patients with PROC are planned to be enrolled and randomized with a 2:1 ratio in an open label manner to the 2 arms (94 patients in the combination treatment arm and 47 patients in the paclitaxel arm) for efficacy and safety evaluation. The randomization will be stratified by country (the United States vs. China), prior bevacizumab use (yes vs. no), and number of prior platinum based therapy treatments (1-2 vs. 3-5 prior platinum regimens). The study will consist of 3 periods. The first period is the Screening Period (Day -24 to 1) during which patients are screened for eligibility according to the inclusion and exclusion criteria. The second period is a Treatment Evaluation Period with a randomized, open-label, two arm parallel design (from starting study treatment until patients have progressive disease [PD], unacceptable toxicity, death, or withdrawal of consent). The PK study will be applied to both the combination treatment arm and control arm. The third period is a Follow up Period (safety evaluation at 30 days after the last dose of study treatment and OS and/or PFS follow up). Patients will be tested at baseline for phosphoinositide 3 kinase (PI3K)/AKT/PTEN pathway alterations and BRCA1/2 mutations by NGS, and/or level of phospho AKT by IHC; the correlation of the efficacy endpoints and biomarker status will be analyzed retrospectively as an exploratory endpoint.

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Eligibility Criteria

Inclusion Criteria:

1. 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).
Toxicities of prior therapy (except alopecia) should have been resolved to less than or equal to grade 1 as per NCI-CTCAE v5.0.
Patients must have GI functions that would allow absorption of afuresertib.
Patient must have a life expectancy of greater than 6 months.
Must have at least one lesion that meets the definition of measurable disease by RECIST 1.1 criteria (Appendix 3).
Patients of childbearing potential must agree to use adequate contraception (barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately.
Must be off strong inhibitors or inducers of CYP3A4/5 treatment, as showed in Appendix 2, for at least 2 weeks from Study Day 1.

Exclusion Criteria:

1. 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.

Human immunodeficiency virus (HIV)-positive patients with 1 or more of the following:

Not receiving highly active antiretroviral therapy
Receiving antiretroviral therapy that may interfere with the study drug (consult the Sponsor for review of medication prior to enrollment)
CD4 count < 350 based on a test within 3 months of the screening visit
An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening
Had a major surgery ≤ 30 days prior to first study treatment at Cycle 1 Day 1.
Presence of grade > 2 neuropathy.
Prior receipt of chemotherapy, PARP inhibitor, bevacizumab, or investigational therapy within 28 days of enrollment or within 5 half lives of the agent, whichever is shorter.
Patients who are pregnant or lactating.
Patients with high risk of tuberculosis infection, based on investigator's clinical assessment, will be screened by tuberculosis screening test, such as the QuantiFERON® TB Gold In Tube test (QFT-GIT) or the T-SPOT®.TB test (T-Spot).

Patients with active hepatitis B (positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C (positive hepatitis C virus [HCV] antibody test at screening) are not allowed to be enrolled in this study. Note:

Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive hepatitis B core antibody [HBcAb] test) are eligible.
Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.

Study is for people with:

Ovarian Cancer

Phase:

Phase 2

Estimated Enrollment:

141

Study ID:

NCT04374630

Recruitment Status:

Recruiting

Sponsor:

Laekna Limited

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There are 29 Locations for this study

See Locations Near You

Arizona Oncology Associates
Phoenix Arizona, 85016, United States More Info
Bradley Monk, MD
Principal Investigator
Arizona Oncology
Tucson Arizona, 85711, United States More Info
Joseph Buscema, MD
Principal Investigator
Highlands Oncology Group
Rogers Arkansas, 72758, United States More Info
Thaddeus Beck, MD
Principal Investigator
Gynecology Oncology Associates Newport Beach
Newport Beach California, 92663, United States More Info
Alberto Mendivil, MD
Principal Investigator
Rocky Mountain Cancer Centers
Littleton Colorado, 80120, United States More Info
Bupathi Manojkumar, MD
Principal Investigator
Kapiolani Medical Center for Women and Children
Honolulu Hawaii, 96826, United States More Info
Michael Carney, MD
Principal Investigator
University of Chicago
Chicago Illinois, 60637, United States More Info
John Moroney, MD
Principal Investigator
Women's Cancer Care
Covington Louisiana, 70433, United States More Info
Patricia Braly, MD
Principal Investigator
Tufts Medical Center
Boston Massachusetts, 02111, United States More Info
John Schorge, MD
Principal Investigator
University of Massachusetts
Worcester Massachusetts, 01605, United States More Info
Susan Zweizig, MD
Principal Investigator
Nebraska Methodist Hospital
Omaha Nebraska, 68114, United States More Info
Brent Tierney, MD
Principal Investigator
MD Anderson Cancer Center at Cooper
Camden New Jersey, 08103, United States More Info
David Warshall, MD
Principal Investigator
Holy Name Medical Center
Teaneck New Jersey, 07666, United States More Info
Maria Schiavone, MD
Principal Investigator
Southwest Women's Oncology Group
Albuquerque New Mexico, 87106, United States More Info
Karen Finkelstein, MD
Principal Investigator
Montefiore Medical Center
Bronx New York, 10467, United States More Info
Nicole Nevadunsky, MD
Principal Investigator
University of Cincinnati Medical Center
Cincinnati Ohio, 45219, United States More Info
Thomas Herzog, MD
Principal Investigator
OHCare Oncology Hematology Care (OHC), Inc. - Kenwood Office
Cincinnati Ohio, 45242, United States More Info
Cynthia Chua, MD
Principal Investigator
Thomas Jefferson University
Philadelphia Pennsylvania, 19107, United States More Info
Richard Scott, MD
Principal Investigator
Abington Memorial Hospital
Willow Grove Pennsylvania, 19090, United States More Info
Mark Shahin, MD
Principal Investigator
Women & Infants Hospital of Rhode Island
Providence Rhode Island, 02905, United States More Info
Cara Mathews, MD
Principal Investigator
Texas Oncology
Austin Texas, 78731, United States More Info
Michael Teneriello, MD
Principal Investigator
Texas Oncology
Fort Worth Texas, 76104, United States More Info
Noelle Cloven, MD
Principal Investigator
Houston Methodist Hospital
Houston Texas, 77030, United States More Info
Aparna Kamat, MD
Principal Investigator
University of Texas Health Science Center at Houston
Houston Texas, 77030, United States More Info
Joseph Lucci, MD
Principal Investigator
USO Texas Oncology
Longview Texas, 75601, United States More Info
Anna Priebe, MD
Principal Investigator
US Texas Oncology
San Antonio Texas, 78240, United States More Info
Joseph de la Garza, MD
Principal Investigator
Baylor Scott & White Medical Center
Temple Texas, 76508, United States More Info
Timothy McCormick, DO
Principal Investigator
Texas Oncology
The Woodlands Texas, 77380, United States More Info
Christine Lee, MD
Principal Investigator
Virginia Oncology Associates
Norfolk Virginia, 23502, United States More Info
Michael McCollum, MD
Principal Investigator
University of Washington/Seattle Cancer Care Alliance
Seattle Washington, 98109, United States More Info
John Liao, MD
Principal Investigator
Beijing Obstetrics & Gynecology Hospital, Capital Medical University
Beijing , , China More Info
Wei Duan, MD
Principal Investigator
Cancer Hospital Chinese Academy of Medical Sciences
Beijing , , China More Info
Lingying Wu, MD
Principal Investigator
Peking University Cancer Hospital
Beijing , , China More Info
Yunong Gao, MD
Principal Investigator
Chongqing University Cancer Hospital
Chongqing , , China More Info
Qi Zhou, MD
Principal Investigator
Sun Yat-sen University Cancer Center
Guangdong , , China More Info
Jihong Liu, MD
Principal Investigator
Harbin Medical University Cancer Hospital
Heilongjiang , , China More Info
Ge Lou, MD
Principal Investigator
Henan Cancer Hospital
Henan , , China More Info
Luo Yanlin, MD
Principal Investigator
Hubei Cancer Hospital
Hubei , , China More Info
Yi HUang, MD
Principal Investigator
Hunan Cancer Hospital
Hunan , , China More Info
Jing Wang, MD
Principal Investigator
Jilin Cancer Hospital
Jilin , , China More Info
Ying Cheng, MD
Principal Investigator
Liaoning Cancer Hospital
Liaoyang , , China More Info
Danbo Wang, MD
Principal Investigator
Qilu Hospital of Shandong University
Shandong , , China More Info
Beijua Kong, MD
Principal Investigator
Obstetrics & Gynecology Hospital of Fudan University
Shanghai , , China More Info
Kang Yu, MD
Principal Investigator
Zhongshan Hospital affiliated to Fudan University
Shanghai , , China More Info
Rong Yu Zang, MD
Principal Investigator
West China Second University Hospital,Sichuan University
Sichuan , , China More Info
Rutie Yin, MD
Principal Investigator
The Second Hospital of Tianjin Medical University
Tianjin , , China More Info
Haitao Wang, MD
Principal Investigator
Women's Hospital school of medicine Zhejiang University
Zhejiang , , China More Info
Weiguo Lv, MD
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Ovarian Cancer

Phase:

Phase 2

Estimated Enrollment:

141

Study ID:

NCT04374630

Recruitment Status:

Recruiting

Sponsor:


Laekna Limited

How clear is this clinincal trial information?

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