Cancer, Ovarian Cancer
Conditions
Keywords
Neoplasms
Brief summary
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.
Interventions
DRUGBBI503
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.
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: 1. Histological or cytological confirmation of epithelial ovarian, primary peritoneal, or fallopian cancer from any previous time point. 2. 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) 3. 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. 4. 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 5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 Key
Exclusion criteria
1. 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.) 2. 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 3. Major surgery ≤28 days before start of treatment 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 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 | The effect of amcasertib (BBI503) on PFS in asymptomatic recurrent ovarian cancer patients with CA-125 elevation |
| Progression Free Survival (PFS)-6 | 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 | The effect of amcasertib (BBI503) on PFS at 6 months in asymptomatic recurrent ovarian cancer patients with CA-125 elevation |
| Objective Response Rate (ORR) | From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 18 months | 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). |
| Overall Survival (OS) at 6 Months | 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, up to 6 months | Defined as the time from enrollment to death due to any cause. |
| Number of Patients With 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. | Assessment of safety of amcasertib in participants by reporting of adverse events and serious adverse events |
Countries
United States
Participant flow
Recruitment details
A total of 13 participants who met all inclusion criteria and no exclusion criteria were enrolled and received treatment at 1 clinical site in the United States.
Pre-assignment details
Participants who died, withdrew consent to survival follow up or were lost to follow up were considered to have completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Participants who were enrolled into the study received amcasertib (BBI503), administered orally, once daily. Dosing began at 200 mg once daily, preferably at bedtime and 2 hours after a meal. Dose modification in case of adverse events was allowed according to following schedule: Full dose: 200 mg daily; Modification Level-1: 100 mg daily; Modification Level-2: 50 mg daily. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Arm A |
|---|---|
| Age, Continuous | 60.6 years STANDARD_DEVIATION 9.56 |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 12 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 13 |
| other Total, other adverse events | 9 / 13 |
| serious Total, serious adverse events | 1 / 13 |
Outcome results
Primary
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).
Time frame: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 weeks
Population: Due to a lack of efficacy in the solid tumor indications that were evaluated in early-stage trials of this compound, the entirety of the amcasertib development was discontinued by the sponsor. Analysis of the DCR was not performed since data were not collected.
Secondary
Number of Patients With Adverse Events
Assessment of safety of amcasertib in participants by reporting of adverse events and serious adverse events
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Number of Patients With Adverse Events | 9 participants |
Secondary
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).
Time frame: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 18 months
Population: Due to a lack of efficacy in the solid tumor indications that were evaluated in early-stage trials of this compound, the entirety of the amcasertib development was discontinued by the sponsor. Analysis of the ORR was not performed since data were not collected.
Secondary
Overall Survival (OS) at 6 Months
Defined as the time from enrollment to death due to any cause.
Time frame: 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, up to 6 months
Population: Due to a lack of efficacy in the solid tumor indications that were evaluated in early-stage trials of this compound, the entirety of the amcasertib development was discontinued by the sponsor. Analysis of the OS at 6 months was not performed since data were not collected.
Secondary
Progression Free Survival (PFS)
The effect of amcasertib (BBI503) on PFS in asymptomatic recurrent ovarian cancer patients with CA-125 elevation
Time frame: 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
Population: Due to a lack of efficacy in the solid tumor indications that were evaluated in early-stage trials of this compound, the entirety of the amcasertib development was discontinued by the sponsor. Analysis of the PFS was not performed since data were not collected.
Secondary
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
Time frame: 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
Population: Due to a lack of efficacy in the solid tumor indications that were evaluated in early-stage trials of this compound, the entirety of the amcasertib development was discontinued by the sponsor. Analysis of the PFS-6 was not performed since data were not collected.