A Study of BBI503 in Asymptomatic Recurrent Ovarian Cancer Patients With CA-125 Elevation

Study Overview
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Brief Summary
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This was an open-label, single-arm, Phase II study in which amcasertib (BBI503) was administered to adult, asymptomatic patients with recurrent ovarian cancer who had elevated CA-125.

Official Title
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A Phase II Clinical Study of BBI503 in Asymptomatic Recurrent Ovarian Cancer Patients With CA-125 Elevation

Conditions
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Cancer, Ovarian Cancer

Intervention / Treatment
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* Drug: BBI503


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Histological or cytological confirmation of epithelial ovarian, primary peritoneal, or fallopian cancer from any previous time point. Recurrent or relapsed after completion of initial therapy of epithelial ovarian, primary peritoneal, or fallopian cancer from any previous time point (includes completion of surgery with or without postoperative chemotherapy, including maintenance chemotherapy) Elevation of CA-125 according to the following definitions: Patients with an elevated CA-125 before chemotherapy and normalization of CA-125 with/after chemotherapy must show evidence of CA-125 greater than or equal to 2 times the upper limit of normal (ULN) on 2 occasions at least 1 week apart Patients with an elevated CA-125 before cancer chemotherapy, which never normalizes, must show evidence of CA-125 greater than or equal to 2 times the nadir value on 2 occasions at least 1 week apart Patients with CA-125 in the normal range before cancer chemotherapy must show evidence of CA-125 greater than or equal to 2 times the ULN on 2 occasions at least 1 week apart For patients who have received subsequent treatment for recurrent cancer, chemotherapy in the above criteria refers to the most recent round of chemotherapy. Patients with a history of ovarian cancer who are asymptomatic and who do not have documented previous CA-125 levels may enroll if the CA-125 is greater than three times the ULN on two occasions, at least one week apart Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 Key exclusion criteria: Symptoms (other than ≤ grade 1 fatigue, anxiety, depression, or other psychological symptoms) that, in the opinion of the treating oncologist, are a direct result of cancer recurrence. (Examples of symptoms that would preclude enrollment include unintentional weight loss, ≥ grade 2 fatigue, and new abdominal pain unrelated to operative procedures for the ovarian malignancy.) Receiving any other investigational agent that would be considered a treatment for the primary neoplasm. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents ≤14 days of first dose of study drug Major surgery ≤28 days before start of treatment History of another primary malignancy with an associated disease-free interval of less than 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or in situ cancer of the cervix.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br> | Drug: BBI503<br>* BBI503 will be administered orally, once daily. Dosing will begin at 200 mg once daily, preferably at bedtime and 2 hours after a meal. Dose modification in case of adverse events is allowed according to the schedule below; Full dose: 200 mg daily, Modification Level-1: 100 mg daily, Modification Level-2: 50 mg daily.<br>* Other names: BBI-503;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Assessed by the Gynecologic Cancer Intergroup (GCIG) guidelines which incorporate both CA-125 response and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (the latter applies to patients who have measurable disease). DCR was defined as the proportion of patients who had an overall response of complete response (CR), partial response (PR), or stable disease (SD). | From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | The effect of amcasertib (BBI503) on PFS in asymptomatic recurrent ovarian cancer patients with CA-125 elevation | The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause, up to 18 months | 
| Progression Free Survival (PFS)-6 | The effect of amcasertib (BBI503) on PFS at 6 months in asymptomatic recurrent ovarian cancer patients with CA-125 elevation | The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause at 6 months | 
| Objective Response Rate (ORR) | Assessed by the Gynecologic Cancer Intergroup (GCIG) guidelines which incorporate both CA-125 response and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (the latter applies to patients who have measurable disease). | From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 18 months | 
| Overall Survival (OS) at 6 Months | Defined as the time from enrollment to death due to any cause. | 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, up to 6 months | 
| Number of Patients With Adverse Events | Assessment of safety of amcasertib in participants by reporting of adverse events and serious adverse events | The time from the date of first treatment, while the patient is taking amcasertib, and for 30 days after stopping therapy, an average of 4 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoplasms