Evaluation of Enzastaurin in the Treatment of Persistent or Recurrent Ovarian or Primary Peritoneal Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00420381
• Collaborator: Gynecologic Oncology Group (Other)
• Enrollment: 28
• Location: 1
• Arm: 1
• Duration (Months): 95
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose is to assess the efficacy and toxicity of the study agent, enzastaurin, in participants with recurrent or persistent ovarian cancer.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Neoplasms; Carcinoma	Drug: enzastaurin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Enzastaurin in the Treatment of Persistent or Recurrent Ovarian or Primary Peritoneal Carcinoma
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: enzastaurin; 1125 mg loading dose then 500 mg, oral, daily, until progressive disease; Other Names: LY317615

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gynecologic Oncology Group 215-854-0770	Philadelphia	Pennsylvania	United States	19103

Sponsors and Collaborators

• Eli Lilly and Company
• Gynecologic Oncology Group

Investigators

• Study Director: Lydia Usha, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00420381
• Other Study ID Numbers: 10738; H6Q-MC-S025
• First Posted: Jan 11, 2007
• Last Update Posted: Dec 19, 2020
• Last Verified: Nov 1, 2020

• Keywords provided by Eli Lilly and Company: Recurrent Cancer
• Additional relevant MeSH terms: Carcinoma

Study Results

Participant Flow

Pre-assignment Detail	Completers are defined as receiving at least one dose of study drug and treated until progressive disease.

Arm/Group Title	Enzastaurin
Arm/Group Description	1125 mg oral loading dose enzastaurin then 500 mg, oral, daily, until progressive disease.
Period Title: Overall Study
STARTED	28
Received at Least One Dose of Study Drug	27
COMPLETED	27
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Enzastaurin
Arm/Group Description	1125 mg oral loading dose enzastaurin then 500 mg, oral, daily, until progressive disease.
Overall Participants	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (10.5)
Sex: Female, Male (Count of Participants)
Female	27 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	27 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.7%
White	26 96.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	27 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival for at Least 6 Months (PFS-6)
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug. 1 participant was censored.

Arm/Group Title	Enzastaurin
Arm/Group Description	1125 mg oral loading dose enzastaurin then 500 mg, oral, daily, until progressive disease.
Measure Participants	26
Number (90% Confidence Interval) [Percentage of participants]	10 37%

2. Primary Outcome

Title	Number of Participants With Adverse Events and Severe Adverse Events
Description	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)

Outcome Measure Data

Analysis Population Description

All enrolled participants.

Arm/Group Title	Enzastaurin
Arm/Group Description	1125 mg oral loading dose enzastaurin then 500 mg, oral, daily, until progressive disease.
Measure Participants	28
Other AEs	27 100%
SAEs	12 44.4%

3. Secondary Outcome

Title	Duration of Progression-Free Survival
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug, 1 participant was censored.

Arm/Group Title	Enzastaurin
Arm/Group Description	1125 mg oral loading dose enzastaurin then 500 mg, oral, daily, until progressive disease.
Measure Participants	26
Median (90% Confidence Interval) [months]	1.9

4. Secondary Outcome

Title	Prognostic Factors: Platinum Sensitivity
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Enzastaurin
Arm/Group Description	1125 mg oral loading dose enzastaurin then 500 mg, oral, daily, until progressive disease.
Measure Participants	27
Refractory Resistant (<6 months)	17 63%
Sensitive (>= 6months)	9 33.3%
Missing	1 3.7%

5. Secondary Outcome

Title	Prognostic Factors: Performance Status
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Enzastaurin
Arm/Group Description	1125 mg oral loading dose enzastaurin then 500 mg, oral, daily, until progressive disease.
Measure Participants	27
Performance Status 0	16 59.3%
Performance Status 1	11 40.7%

6. Secondary Outcome

Title	Overall Survival
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. 8 participants were censored.

Arm/Group Title	Enzastaurin
Arm/Group Description	1125 mg oral loading dose enzastaurin then 500 mg, oral, daily, until progressive disease.
Measure Participants	19
Median (90% Confidence Interval) [Months]	15.1

Adverse Events

Adverse Event Reporting Description	All participants in study.
Arm/Group Title	Enzastaurin
Arm/Group Description	1125 mg oral loading dose enzastaurin then 500 mg, oral, daily, until progressive disease.
All Cause Mortality
	Enzastaurin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Enzastaurin
	Affected / at Risk (%)	# Events
Total	12/28 (42.9%)
Blood and lymphatic system disorders
Hemorrhage, gi	2/28 (7.1%)	2
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	1/28 (3.6%)	1
Cardiac disorders
Hypertension	1/28 (3.6%)	1
Gastrointestinal disorders
Ascites (non-malignant)	2/28 (7.1%)	2
Constipation	2/28 (7.1%)	3
Dehydration	1/28 (3.6%)	1
Diarrhea	1/28 (3.6%)	2
Distension/bloating, abdominal	1/28 (3.6%)	2
Gastrointestinal - other (Ascites Malignant)	1/28 (3.6%)	1
Ileus, gi (functional obstruction of bowel, i.e., neuroconstipation)	1/28 (3.6%)	1
Incontinence, anal	1/28 (3.6%)	1
Nausea	2/28 (7.1%)	2
Obstruction, gi	4/28 (14.3%)	4
Vomiting	4/28 (14.3%)	5
General disorders
Fatigue (asthenia, lethargy, malaise)	2/28 (7.1%)	3
Insomnia	1/28 (3.6%)	1
Weight loss	1/28 (3.6%)	1
Death not associated with ctcae term	3/28 (10.7%)	3
Edema: limb	1/28 (3.6%)	2
Pain	4/28 (14.3%)	7
Metabolism and nutrition disorders
Creatinine	1/28 (3.6%)	2
Potassium, serum-high (hyperkalemia)	1/28 (3.6%)	1
Sodium, serum-low (hyponatremia)	1/28 (3.6%)	1
Nervous system disorders
Dizziness	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	1/28 (3.6%)	1
Atelectasis	1/28 (3.6%)	1
Dyspnea (shortness of breath)	3/28 (10.7%)	5
Pulmonary/upper respiratory - other (Malignant Pleural Effusion)	1/28 (3.6%)	2
Skin and subcutaneous tissue disorders
Rash/desquamation	1/28 (3.6%)	2
Vascular disorders
Thrombosis/thrombus/embolism	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	Enzastaurin
	Affected / at Risk (%)	# Events
Total	27/28 (96.4%)
Gastrointestinal disorders
Anorexia	10/28 (35.7%)	16
Ascites (non-malignant)	2/28 (7.1%)	3
Constipation	9/28 (32.1%)	18
Diarrhea	13/28 (46.4%)	20
Distension/bloating, abdominal	2/28 (7.1%)	2
Dry mouth/salivary gland (xerostomia)	3/28 (10.7%)	3
Heartburn/dyspepsia	2/28 (7.1%)	2
Nausea	10/28 (35.7%)	23
Taste alteration (dysgeusia)	2/28 (7.1%)	2
Vomiting	5/28 (17.9%)	6
General disorders
Fatigue (asthenia, lethargy, malaise)	16/28 (57.1%)	35
Insomnia	2/28 (7.1%)	2
Sweating (diaphoresis)	2/28 (7.1%)	2
Edema: limb	6/28 (21.4%)	9
Mood alteration	2/28 (7.1%)	3
Pain	17/28 (60.7%)	32
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	4/28 (14.3%)	9
Allergy/immunology - other	2/28 (7.1%)	2
Infections and infestations
Infection with normal anc or grade 1 or 2 neutrophils	6/28 (21.4%)	30
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	3/28 (10.7%)	5
Alkaline phosphatase	3/28 (10.7%)	4
Calcium, serum-low (hypocalcemia)	2/28 (7.1%)	2
Creatinine	2/28 (7.1%)	2
Glomerular filtration rate	3/28 (10.7%)	4
Glucose, serum-high (hyperglycemia)	3/28 (10.7%)	6
Magnesium, serum-low (hypomagnesemia)	2/28 (7.1%)	3
Potassium, serum-high (hyperkalemia)	2/28 (7.1%)	2
Potassium, serum-low (hypokalemia)	2/28 (7.1%)	3
Sodium, serum-low (hyponatremia)	4/28 (14.3%)	8
Renal and urinary disorders
Urine color change	3/28 (10.7%)	7
Respiratory, thoracic and mediastinal disorders
Cough	2/28 (7.1%)	2
Dyspnea (shortness of breath)	8/28 (28.6%)	10
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)	2/28 (7.1%)	3
Rash/desquamation	2/28 (7.1%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.