Carcinoma, Neoplasms, Ovarian Cancer
Conditions
Keywords
Recurrent Cancer
Brief summary
The purpose is to assess the efficacy and toxicity of the study agent, enzastaurin, in participants with recurrent or persistent ovarian cancer.
Interventions
DRUGenzastaurin
1125 mg loading dose then 500 mg, oral, daily, until progressive disease
Sponsors
Gynecologic Oncology Group
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have recurrent or persistent epithelial ovarian or primary peritoneal carcinoma. * All participants must have measurable disease. * Participants must have at least one target lesion to be used to assess response on this protocol. * Participants must not be eligible for a higher priority GOG protocol, if one exists. * Participants who have received one prior regimen must have a GOG Performance Status of 0, 1, or 2. Participants who have received two prior regimens must have a GOG Performance Status of 0 or 1. * Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy is permitted. * Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least four weeks prior to registration. * Participants must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. * Participants must NOT have received any non-cytotoxic therapy for management of recurrent or persistent disease. * Participants of child-bearing potential must have a negative serum pregnancy test prior to study entry and be practicing an effective form of contraception (for example, intrauterine device \[IUD\], birth control pills, or barrier device) during and for 3 months after discontinuation of study treatment.
Exclusion criteria
* Participants with previous enzastaurin treatment. * Participants who have received radiation to more than 25% of marrow-bearing areas * Participants with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy. * Participants who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. * Participants who are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin (refer to Concomitant Medications for a discussion of enzyme inducing anti-epileptic drugs \[EIAEDs\]). * Participants who are receiving concurrent administration of any other systemic anticancer therapy except for a biphosphonate if patient has bony metastases. * Participants who have received prior therapy with non-cytotoxic agents (i.e. bevacizumab). * Participants with serious concomitant systemic disorders (for example, active infection or abnormal electrocardiogram (ECG) indicative of cardiac disease) that, in the opinion of the investigator, would compromise the safety of the patient and his/her ability to complete the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival for at Least 6 Months (PFS-6) | Baseline through 6 months | Data presented are the percentage of participants without progressive disease (PD) or death from any cause 6 months after registration. PD was a 25% increase in the sum of products of all measurable lesions (or 2 largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
| Number of Participants With Adverse Events and Severe Adverse Events | Baseline through end of study (Up to 45 months) | Data presented are the number of participants who experienced 1 or more adverse events (AEs) (all causalities and drug-related) and serious AEs (SAEs). A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this record. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Progression-Free Survival | Baseline to disease progression (Up to 38 months) | PFS is defined as the rate of PFS from the date of diagnosis to the first date of objectively determined progressive disease (based on radiological assessment) or death from any cause. It is assumed that PFS follows an exponential distribution. |
| Prognostic Factors: Platinum Sensitivity | Baseline | Participants who had disease progression within 6 months of ending their last regimen of platinum therapy were considered platinum resistant. Participants who had disease progression between 6 and 12 months of ending their last platinum regimen were considered platinum sensitive. Participants who had disease progression beyond 12 months of ending their last platinum regimen were also considered platinum sensitive. |
| Prognostic Factors: Performance Status | Baseline | Performance Status 0 = Fully active, able to carry on all pre-disease performance without restriction Performance Status 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, e.g., light housework, office work. |
| Overall Survival | Baseline through end of study (Up to 45 months) | Overall survival (OS) time is defined as the time from the date of diagnosis to the date of death from any cause. For participants who are still alive at the time of analysis, survival time will be censored at the last contact date. |
Countries
United States
Participant flow
Pre-assignment details
Completers are defined as receiving at least one dose of study drug and treated until progressive disease.
Participants by arm
| Arm | Count |
|---|---|
| Enzastaurin 1125 mg oral loading dose enzastaurin then 500 mg, oral, daily, until progressive disease. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Enzastaurin |
|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 10.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Region of Enrollment United States | 27 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 27 / 28 |
| serious Total, serious adverse events | 12 / 28 |
Outcome results
Primary
Number of Participants With Adverse Events and Severe Adverse Events
Data presented are the number of participants who experienced 1 or more adverse events (AEs) (all causalities and drug-related) and serious AEs (SAEs). A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this record.
Time frame: Baseline through end of study (Up to 45 months)
Population: All enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enzastaurin | Number of Participants With Adverse Events and Severe Adverse Events | Other AEs | 27 Participants |
| Enzastaurin | Number of Participants With Adverse Events and Severe Adverse Events | SAEs | 12 Participants |
Primary
Progression-free Survival for at Least 6 Months (PFS-6)
Data presented are the percentage of participants without progressive disease (PD) or death from any cause 6 months after registration. PD was a 25% increase in the sum of products of all measurable lesions (or 2 largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Time frame: Baseline through 6 months
Population: All participants who received at least 1 dose of study drug. 1 participant was censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enzastaurin | Progression-free Survival for at Least 6 Months (PFS-6) | 10 Percentage of participants |
Secondary
Duration of Progression-Free Survival
PFS is defined as the rate of PFS from the date of diagnosis to the first date of objectively determined progressive disease (based on radiological assessment) or death from any cause. It is assumed that PFS follows an exponential distribution.
Time frame: Baseline to disease progression (Up to 38 months)
Population: All participants who received at least 1 dose of study drug, 1 participant was censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzastaurin | Duration of Progression-Free Survival | 1.9 months |
Secondary
Overall Survival
Overall survival (OS) time is defined as the time from the date of diagnosis to the date of death from any cause. For participants who are still alive at the time of analysis, survival time will be censored at the last contact date.
Time frame: Baseline through end of study (Up to 45 months)
Population: All participants who received at least one dose of study drug. 8 participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzastaurin | Overall Survival | 15.1 Months |
Secondary
Prognostic Factors: Performance Status
Performance Status 0 = Fully active, able to carry on all pre-disease performance without restriction Performance Status 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, e.g., light housework, office work.
Time frame: Baseline
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enzastaurin | Prognostic Factors: Performance Status | Performance Status 0 | 16 Participants |
| Enzastaurin | Prognostic Factors: Performance Status | Performance Status 1 | 11 Participants |
Secondary
Prognostic Factors: Platinum Sensitivity
Participants who had disease progression within 6 months of ending their last regimen of platinum therapy were considered platinum resistant. Participants who had disease progression between 6 and 12 months of ending their last platinum regimen were considered platinum sensitive. Participants who had disease progression beyond 12 months of ending their last platinum regimen were also considered platinum sensitive.
Time frame: Baseline
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enzastaurin | Prognostic Factors: Platinum Sensitivity | Refractory Resistant (<6 months) | 17 Participants |
| Enzastaurin | Prognostic Factors: Platinum Sensitivity | Sensitive (>= 6months) | 9 Participants |
| Enzastaurin | Prognostic Factors: Platinum Sensitivity | Missing | 1 Participants |