Ovarian Carcinoma
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to evaluate the anti-tumour activity of alisertib (MLN8237) in the treatment of participants with platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinomas.
Detailed description
The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. This study looked at the antitumor activity by response rate who would take alisertib. The study enrolled 31 patients. Participants were categorized as per the disease state into 2 categories, refractory and resistant. Participants received: • Alisertib 50 mg All participants took alisertib 50 mg capsules every 12 hours each day for 7 days followed by a 14-day rest period in a 21-day cycle (up to 26 cycles). This multi-center trial was conducted in France, Poland and the United States. The overall time to participate in this study was 12 months, unless it is determined that a participant would benefit from continued therapy beyond 12 months. Participants made multiple visits to the clinic, and were contacted up to a maximum of every 12 weeks up to 12 months after last dose of study drug for follow-up assessments.
Interventions
DRUGAlisertib
Alisertib capsules
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female participants 18 years or older. 2. Histologically or cytologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 4. Postmenopausal at least 1 year, OR * Surgically sterile, OR * If childbearing potential, agree to 2 effective methods of nonhormonal contraception, or agree to completely abstain from heterosexual intercourse. 5. Able to provide written informed consent. 6. Within 7 days before study: * Absolute neutrophils (ANC) ≥ 1,500/μL * Platelets ≥100,000/ μL * Total bilirubin must be \< 1.5 times upper limit of the normal (ULN) * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be ≤ 2.5 times the ULN. AST and ALT may be elevated up to 5 times the ULN if ascribed to metastatic liver disease. * Creatinine clearance ≥ 30 mL/minute 7. Platinum-refractory or -resistant disease. 8. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) OR Cancer antigen (CA) 125 level of \> 40 units/mL AND clinical evidence disease. 9. Recovered from effects of prior therapy.
Exclusion criteria
1. Pregnant or lactating. 2. Serious illness that could interfere with protocol completion. 3. Investigational treatment 28 days prior to first dose. 4. Maximum 4 prior systemic therapies: 2 platinum-based, 1 nonplatinum cytotoxic, 1 biological. 5. Known Central Nervous System metastases. 6. Prior allogeneic bone marrow or organ transplantation. 7. Radiotherapy within 21 days prior to first dose. 8. Radiotherapy to \> 25% bone marrow. 9. Major surgery or infection requiring systemic antibiotic therapy within 14 days prior to first dose. 10. Inability to swallow orally administered medication. 11. Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected. 12. Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Combined Best Overall Response Rate Based on Investigator Assessment | Every 2 cycles up to 12 months until progressive disease (PD); Participants who discontinue study drug before PD: Follow-Up (FU)-every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months) | Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must have been confirmed by a fourth sample 28 days later (a total of 4 samples required) or A serial decrease of \> 75% over 3 samples; the third sample was to be obtained 28 days after the second (a total of 3 samples required). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration Of Response (DOR) | Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months) | DOR is defined as the time from the date of first documentation of a confirmed response to the date of first documented PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions. |
| Time To Progression (TTP) | Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months) | TTP is defined as the time in days from the date of first study drug administration to the date of first documentation of PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions. |
| Clinical Benefit Rate | Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months) | Clinical benefit rate is defined as the percentage of participants with response and stable disease (SD), where in order for SD to qualify as having clinical benefit, there must be no progression of neoplastic disease for at least 4 treatment cycles. |
| Progression Free Survival (PFS) | Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months) | PFS is defined as the time in days from the date of first study drug administration to the date of first documented Progressive Disease (PD) or death. PD is defined as 20% increase in the sum of the longest diameter of target lesions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level \> 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125. For a participant who has not progressed and has not died, PFS is censored at the last response assessment that is stable disease (SD) or better. |
| Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Baseline, Cycle 1 Days 8 and 15, then Day 1 of every cycle (21 days), End of Treatment, End of Study/FU every 12 weeks for up to 12 months (Up to 22 Months) | Vital signs included blood pressure, pulse rate, and oral temperature collected throughout the study. . A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug. |
| Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Baseline, Cycle 1 Days 8 and 15, then Every cycle Days 1, 8 and 15 to End of Treatment Up to 18.0 Months | Laboratory tests included Hematology and Chemistry. Abnormal laboratory value were assessed as an AE if the value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
| Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | First dose to 30 days past last dose (Up to 18.9 Months) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 17 investigative sites in France, Poland and the United States from 23 March 2009 to 27 January 2011.
Pre-assignment details
Participants with a diagnosis of Platinum-refractory and Platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma received 50 mg alisertib twice daily for 7 days in 21-day cycles.
Participants by arm
| Arm | Count |
|---|---|
| Alisertib 50 mg (Platinum-Refractory) Alisertib 50 mg, capsules, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 26 Cycles). Platinum-refractory disease is characterized by a lack of response, progression, or recurrence of disease during a course of platinum-based therapy. | 6 |
| Alisertib 50 mg (Platinum-Resistant) Alisertib 50 mg, capsules, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 26 Cycles). Platinum-resistant disease is characterized by progression or recurrence of malignant disease within 6 months after completion of a platinum-based regimen. | 25 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Reason Not Specified | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Alisertib 50 mg (Platinum-Refractory) | Alisertib 50 mg (Platinum-Resistant) | Total |
|---|---|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 15.38 | 56.6 years STANDARD_DEVIATION 14.19 | 57.0 years STANDARD_DEVIATION 14.18 |
| Body Surface Area (BSA) | 1.72 meter (m)^2 STANDARD_DEVIATION 0.167 | 1.72 meter (m)^2 STANDARD_DEVIATION 0.223 | 1.72 meter (m)^2 STANDARD_DEVIATION 0.212 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG Performance Status = 0 | 2 participants | 18 participants | 20 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG Performance Status = 1 | 4 participants | 7 participants | 11 participants |
| Height | 162.0 centimeter (cm) STANDARD_DEVIATION 4.83 | 160.9 centimeter (cm) STANDARD_DEVIATION 7.76 | 161.0 centimeter (cm) STANDARD_DEVIATION 7.34 |
| Primary diagnosis Epithelial Ovarian | 5 participants | 20 participants | 25 participants |
| Primary diagnosis Fallopian Tube | 0 participants | 1 participants | 1 participants |
| Primary diagnosis Primary Peritoneal Carcinoma | 1 participants | 4 participants | 5 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 3 participants | 22 participants | 25 participants |
| Race/Ethnicity, Customized Not Reported | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized White | 6 participants | 24 participants | 30 participants |
| Sex: Female, Male Female | 6 Participants | 25 Participants | 31 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight | 65.16 kilogram (kg) STANDARD_DEVIATION 9.638 | 68.22 kilogram (kg) STANDARD_DEVIATION 17.227 | 67.63 kilogram (kg) STANDARD_DEVIATION 15.951 |
| Years Since Initial Diagnosis | 1.59 years STANDARD_DEVIATION 0.736 | 2.26 years STANDARD_DEVIATION 1.448 | 2.13 years STANDARD_DEVIATION 1.356 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 24 / 25 |
| serious Total, serious adverse events | 4 / 6 | 7 / 25 |
Outcome results
Primary
Combined Best Overall Response Rate Based on Investigator Assessment
Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must have been confirmed by a fourth sample 28 days later (a total of 4 samples required) or A serial decrease of \> 75% over 3 samples; the third sample was to be obtained 28 days after the second (a total of 3 samples required).
Time frame: Every 2 cycles up to 12 months until progressive disease (PD); Participants who discontinue study drug before PD: Follow-Up (FU)-every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)
Population: Response-evaluable population is defined as all participants who have measurable neoplastic disease according to the RECIST criteria OR participants with a CA 125 level \> 40 units/milliliter (mL) and clinical evidence of neoplastic disease and received at least 1 dose of alisertib and have at least 1 post-baseline response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alisertib 50 mg (Platinum-Refractory) | Combined Best Overall Response Rate Based on Investigator Assessment | 0 percentage of participants |
| Alisertib 50 mg (Platinum-Resistant) | Combined Best Overall Response Rate Based on Investigator Assessment | 12 percentage of participants |
Secondary
Clinical Benefit Rate
Clinical benefit rate is defined as the percentage of participants with response and stable disease (SD), where in order for SD to qualify as having clinical benefit, there must be no progression of neoplastic disease for at least 4 treatment cycles.
Time frame: Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)
Population: Response-evaluable population is defined as all participants who have measurable neoplastic disease according to the RECIST criteria OR participants with a CA 125 level \> 40 units/mL and clinical evidence of neoplastic disease and receive at least 1 dose of alisertib and have at least 1 post-baseline response assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alisertib 50 mg (Platinum-Refractory) | Clinical Benefit Rate | 0 percentage of participants |
| Alisertib 50 mg (Platinum-Resistant) | Clinical Benefit Rate | 32 percentage of participants |
Secondary
Duration Of Response (DOR)
DOR is defined as the time from the date of first documentation of a confirmed response to the date of first documented PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions.
Time frame: Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)
Population: Due to study termination, there was insufficient data to perform this analysis.
Secondary
Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events
Laboratory tests included Hematology and Chemistry. Abnormal laboratory value were assessed as an AE if the value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Baseline, Cycle 1 Days 8 and 15, then Every cycle Days 1, 8 and 15 to End of Treatment Up to 18.0 Months
Population: Safety Population is defined as all participants who received any amount of alisertib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Neutropenia | 3 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Anaemia | 2 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Leukopenia | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Thrombocytopenia | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Dehydration | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypokalaemia | 2 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase increased | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hyperglycaemia | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypomagnesaemia | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood alkaline phosphatase increased | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Febrile neutropenia | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hyponatraemia | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Haemoglobin decreased | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Granulocytopenia | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Neutrophil count increased | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | White blood cell count increased | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hyperbilirubinaemia | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Lymphopenia | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hyperkalaemia | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypernatraemia | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypercholesterolaemia | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Transaminases increased | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Granulocyte count decreased | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood calcium increased | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood magnesium decreased | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Platelet count decreased | 1 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood albumin decreased | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Creatinine renal clearance decreased | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypoxia | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Bacteraemia | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Neutrophil count increased | 2 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Neutropenia | 17 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Granulocyte count decreased | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Anaemia | 14 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | White blood cell count increased | 2 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Leukopenia | 11 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood albumin decreased | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Thrombocytopenia | 8 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hyperbilirubinaemia | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Dehydration | 7 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood calcium increased | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypokalaemia | 4 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Lymphopenia | 0 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase increased | 6 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypoxia | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 6 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hyperkalaemia | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hyperglycaemia | 4 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood magnesium decreased | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypomagnesaemia | 4 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypernatraemia | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood alkaline phosphatase increased | 4 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Creatinine renal clearance decreased | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Febrile neutropenia | 3 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypercholesterolaemia | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hyponatraemia | 2 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Platelet count decreased | 0 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Haemoglobin decreased | 2 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Transaminases increased | 0 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Granulocytopenia | 2 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Bacteraemia | 0 participants |
Secondary
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events
Vital signs included blood pressure, pulse rate, and oral temperature collected throughout the study. . A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Baseline, Cycle 1 Days 8 and 15, then Day 1 of every cycle (21 days), End of Treatment, End of Study/FU every 12 weeks for up to 12 months (Up to 22 Months)
Population: Safety Population is defined as all participants who received any amount of alisertib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Pyrexia | 2 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Dyspnoea | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Weight decreased | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypertension | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Dyspnoea exertional | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Bradycardia | 0 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Shock | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Shock | 0 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Pyrexia | 6 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypertension | 2 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Dyspnoea | 4 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Bradycardia | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Weight decreased | 3 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Dyspnoea exertional | 1 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Tachycardia | 2 participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: First dose to 30 days past last dose (Up to 18.9 Months)
Population: Safety Population is defined as all participants who received any amount of alisertib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AE | 6 participants |
| Alisertib 50 mg (Platinum-Refractory) | Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAE | 4 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AE | 24 participants |
| Alisertib 50 mg (Platinum-Resistant) | Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAE | 7 participants |
Secondary
Progression Free Survival (PFS)
PFS is defined as the time in days from the date of first study drug administration to the date of first documented Progressive Disease (PD) or death. PD is defined as 20% increase in the sum of the longest diameter of target lesions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level \> 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125. For a participant who has not progressed and has not died, PFS is censored at the last response assessment that is stable disease (SD) or better.
Time frame: Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)
Population: Response-evaluable population is defined as all participants who have measurable neoplastic disease according to RECIST criteria OR participants with CA 125 level \> 40 units/mL and clinical evidence of neoplastic disease and received at least 1 dose of alisertib and have at least 1 post-baseline response assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alisertib 50 mg (Platinum-Refractory) | Progression Free Survival (PFS) | 36.5 days |
| Alisertib 50 mg (Platinum-Resistant) | Progression Free Survival (PFS) | 77.0 days |
Secondary
Time To Progression (TTP)
TTP is defined as the time in days from the date of first study drug administration to the date of first documentation of PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions.
Time frame: Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)
Population: Due to study termination, there was insufficient data to perform this analysis.