Platinum-resistant Ovarian CancerPhase 2PROFECTA-IINCT04374630
Study With Afuresertib and Paclitaxel in Platinum Resistant Ovarian
A Phase 2 study testing Paclitaxel and Afuresertib in people with Platinum-resistant Ovarian Cancer, run by Laekna Limited at 47 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Platinum-resistant Ovarian Cancer
- What is being tested?
- Paclitaxel and Afuresertib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 47 sitesin 2 countries
- Study dates
- 7 Jul 2020to 28 Jun 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
47 sites in 2 countries.
47 sites in 2 countries
United States30 sites
Southwest Women's Oncology Group
Albuquerque, New Mexico, 87106
Texas Oncology
Austin, Texas, 78731
Tufts Medical Center
Boston, Massachusetts, 02111
MD Anderson Cancer Center at Cooper
Camden, New Jersey, 08103
University of Chicago
Chicago, Illinois, 60637
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
OHCare Oncology Hematology Care (OHC), Inc. - Kenwood Office
Cincinnati, Ohio, 45242
Women's Cancer Care
Covington, Louisiana, 70433
Texas Oncology
Fort Worth, Texas, 76104
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Houston Methodist Hospital
Houston, Texas, 77030
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Rocky Mountain Cancer Centers
Littleton, Colorado, 80120
USO Texas Oncology
Longview, Texas, 75601
Gynecology Oncology Associates Newport Beach
Newport Beach, California, 92663
Virginia Oncology Associates
Norfolk, Virginia, 23502
Nebraska Methodist Hospital
Omaha, Nebraska, 68114
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Arizona Oncology Associates
Phoenix, Arizona, 85016
Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
Highlands Oncology Group
Rogers, Arkansas, 72758
US Texas Oncology
San Antonio, Texas, 78240
University of Washington/Seattle Cancer Care Alliance
Seattle, Washington, 98109
Holy Name Medical Center
Teaneck, New Jersey, 07666
Baylor Scott & White Medical Center
Temple, Texas, 76508
Montefiore Medical Center
The Bronx, New York, 10467
Texas Oncology
The Woodlands, Texas, 77380
Arizona Oncology
Tucson, Arizona, 85711
Abington Memorial Hospital
Willow Grove, Pennsylvania, 19090
University of Massachusetts
Worcester, Massachusetts, 01605
China17 sites
Beijing Obstetrics & Gynecology Hospital, Capital Medical University
Beijing
Cancer Hospital Chinese Academy of Medical Sciences
Beijing
Peking University Cancer Hospital
Beijing
Chongqing University Cancer Hospital
Chongqing
Sun Yat-sen University Cancer Center
Guangdong
Harbin Medical University Cancer Hospital
Heilongjiang
Henan Cancer Hospital
Henan
Hubei Cancer Hospital
Hubei
Hunan Cancer Hospital
Hunan
Jilin Cancer Hospital
Jilin City
Liaoning Cancer Hospital
Liaoyang
Qilu Hospital of Shandong University
Shandong
Obstetrics & Gynecology Hospital of Fudan University
Shanghai
Zhongshan Hospital affiliated to Fudan University
Shanghai
West China Second University Hospital,Sichuan University
Sichuan
The Second Hospital of Tianjin Medical University
Tianjin
Women's Hospital school of medicine Zhejiang University
Zhejiang
About this study
Official title: An Open Label Randomized Active Controlled Phase II Clinical Study to Assess the Efficacy and Safety of Afuresertib Plus Paclitaxel Versus Paclitaxel in Patients With Platinum-Resistant Ovarian Cancer
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.
Read the detailed 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.
- Conditions
- Platinum-resistant Ovarian Cancer
- Being tested
- Paclitaxel, Afuresertib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Commercially available paclitaxel for IV administration will be obtained by clinical sites in US.
AfuresertibDrug
Also called LAE002
Afuresertib tablet, intended for daily oral administration.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival(PFS ) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Radiographic imaging will be performed and assessed by investigators to evaluate the duration of progress-free survival(PFS) based on RECIST 1.1
Measured: From first dose, evaluate every 6 weeks × 30 weeks, then change to every 8 weeks until study completion, assessed up to 40 months. Progress-free survival (PFS) is defined as from randomization to disease progression or death due to any reason
Secondary outcomes (12)
Objective Response Rate (ORR) According to RECIST 1.1
To further evaluate the clinical efficacy via objective response rate
Measured: The percentage of objective response achieved, objective response is from randomization to either complete response (CR) or partial response (PR) . Evaluate every 6 weeks × 30 weeks, then change to every 8 weeks, up to 40 months
Duration of Response (DOR) According to RECIST 1.1
To further evaluate the clinical efficacy via duration of response
Measured: Evaluate every 6 weeks × 30 weeks, change to every 8 weeks, up to 40 months. DOR is from first observation of response (complete response (CR) or partial response( PR)) until first observation of disease progression or death, whichever occurs first.
Disease Control Rate (DCR) According to RECIST 1.1
To further evaluate the clinical efficacy via Disease control rate
Measured: the percentage of participant who have achieved complete response(CR), partial response (PR) or stable disease(SD) from first study treatment to discontinued study treatment. Evaluate every 6 weeks × 30 weeks, change to every 8 weeks, up to 40 months.
Overall Survival (OS)
To further evaluate the clinical efficacy via OS collection
Measured: OS is defined from date of randomization until death date for any cause. Evaluated from randomization to study completion which is 105 events, up to 40 months.
Cancer Antigen 125 (CA-125) Response (Gynecological Cancer Intergroup [GCIG])
To further evaluate the clinical efficacy via cancer antigen 125 (CA125) response rate
Measured: every 6 weeks × 30 weeks from Baseline , then every 8 weeks through study completion of 105 PFS events achievement, up to 40 months
Area Under the Curve in the Inter-dose Interval Period After First Dose (AUCτ)
To Characterize Pharmacokinetics (PK) of afuresertib and paclitaxel in patients with PROC under combination therapy of afuresertib plus paclitaxel at steady-state via AUCτ
Measured: Samples collected on Cycle1Day1 (a Cycle is 21 days) of pre-dose and at 1h (at the end of paclitaxel infusion), 2h, 3h, 4h, 8h and 24 hours post-dose
Area Under the Curve in the Inter-dose Interval Period at Steady State (AUCτ_SS)
To Characterize Pharmacokinetics (PK) of afuresertib and paclitaxel in patients with PROC under combination therapy of afuresertib plus paclitaxel, or paclitaxel alone at steady-state via AUCτ_SS
Measured: sample collection on cycle2 Day 1 (21days in 1 cycle) of pre-dose and at 0.5h, 1h (at the end of paclitaxel infusion), 2h, 3h, 4h, 8h and 24 hours post-dose
Maximum Concentration After First Dose (Cmax)
To Characterize Pharmacokinetics (PK) of afuresertib and paclitaxel in patients with PROC under combination therapy of afuresertib plus paclitaxel at steady-state via Cmax
Measured: Samples collected on Cycle1Day1 (a Cycle is 21 days) of pre-dose and at 1h (at the end of paclitaxel infusion), 2h, 3h, 4h, 8h and 24 hours post-dose
Maximum Concentration at Steady State (Cmax_SS)
To Characterize Pharmacokinetics (PK) of afuresertib and paclitaxel in patients with PROC under combination therapy of afuresertib plus paclitaxel, or paclitaxel alone at steady-state via Cmax_SS
Measured: sample collection on cycle2 Day 1 (21days in 1 cycle) of pre-dose and at 0.5h, 1h (at the end of paclitaxel infusion), 2h, 3h, 4h, 8h and 24 hours post-dose
Time to Maximum Concentration After First Dose (Tmax) To Explore Potential Effect of Coadministration of Afuresertib
To Characterize Pharmacokinetics (PK) of afuresertib in patients with PROC under combination therapy of afuresertib plus paclitaxel at steady-state via Tmax
Measured: Samples collected on Cycle1Day1 (a Cycle is 21 days) of pre-dose and at 1h (at the end of paclitaxel infusion), 2h, 3h, 4h, 8h and 24 hours post-dose
Time to Maximum Concentration at Steady State (Tmax_SS)
To Characterize Pharmacokinetics (PK) of afuresertib and paclitaxel in patients with PROC under combination therapy of afuresertib plus paclitaxel, or paclitaxel alone at steady-state via Tmax_SS
Measured: sample collection on cycle2 Day 1 (21days in 1 cycle) of pre-dose and at 0.5h, 1h (at the end of paclitaxel infusion), 2h, 3h, 4h, 8h and 24 hours post-dose
Trough Concentration at Steady State (Ctrough_SS)
To Characterize Pharmacokinetics (PK) of afuresertib and paclitaxel in patients with PROC under combination therapy of afuresertib plus paclitaxel, or paclitaxel alone at steady state via Ctrough_SS
Measured: Samples collected on Cycle2Day1was assessed (a Cycle is 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2020
- Study start7 Jul 2020
- Primary completion31 Oct 2023
- Study completion28 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Platinum-resistant Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laekna Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Herzog Thomas, Professor, Principal investigator, University of Cincinnati Medical Center/USA/1010
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04374630
- Sponsor's protocol ID
- LAE002INT2001
- Acronym
- PROFECTA-II
- Status last verified
- Oct 2026
- First submitted
- 2 Apr 2020
- Last updated
- 19 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No