Enzastaurin in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer or Primary Peritoneal Cancer

• ClinicalTrials.gov Identifier: NCT00407758
• Recruitment Status: Completed
• First Posted: December 5, 2006
• Results First Posted: November 21, 2017
• Last Update Posted: March 20, 2019
• Sponsor: Gynecologic Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): GOG Foundation ( Gynecologic Oncology Group )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Ovarian Cancer; Primary Peritoneal Cavity Cancer
• Intervention: Drug: enzastaurin hydrochloride
• Enrollment: 28

Participant Flow

Recruitment Details	This trial was opened to patient entry on November 6, 2006 and was closed to accrual on May 7, 2007.
Pre-assignment Details

Arm/Group Title	Enzastaurin
Arm/Group Description	Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
Period Title: Overall Study
Started	28
Completed [1]	27
Not Completed	1
Reason Not Completed
ineligible -improper prior treatment	1
[1] Eligible and treated patients.

Baseline Characteristics

Arm/Group Title		Enzastaurin
Arm/Group Description		Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
Overall Number of Baseline Participants		27
Baseline Analysis Population Description		Eligible and treated patients
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
	40-49 years	4 14.8%
	50-59 years	10 37.0%
	60-69 years	6 22.2%
	70-79 years	7 25.9%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
	Female	27 100.0%
	Male	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	1 3.7%
	White	26 96.3%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0
Description	RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above.
Time Frame	CT scan or MRI if used to follow lesions for measurable disease every other cycle for the first 6 months; every 6 months thereafter until disease progression for up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Enzastaurin
Arm/Group Description:	Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
Overall Number of Participants Analyzed	27
Measure Type: Count of Participants; Unit of Measure: Participants
Partial response	2
Complete response	0

2. Primary Outcome

Title	Progression-free Survival > 6 Months Using RECIST 1.0
Description	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Time Frame	CT scan or MRI if used to follow lesion for measurable disease every other cycle for first 6 months; every 6 months thereafter until disease progression for up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Enzastaurin
Arm/Group Description:	Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
Overall Number of Participants Analyzed	27
Measure Type: Count of Participants; Unit of Measure: Participants
PFS> 6 months - Yes	3
PFS>6months - No	24

3. Primary Outcome

Title	Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Description	Number of participants with a maximum grade of 3 or higher during the treatment period.
Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Enzastaurin
Arm/Group Description:	Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
Overall Number of Participants Analyzed	27
Measure Type: Count of Participants; Unit of Measure: Participants
Anemia	1
Constitutional	5
Gastrointestinal	11
Infection	2
Metabolic	4
Other Neurological	1
Pain	5
Pulmonary	5
Vascular	1
Death, not CTC coded	3

4. Secondary Outcome

Title	Duration Overall Survival
Description	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Time Frame	Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Enzastaurin
Arm/Group Description:	Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
Overall Number of Participants Analyzed	27
Median (90% Confidence Interval); Unit of Measure: months
	15.1 [1]; (6.5 to NA)

[1]

Upper limit not yet reached

5. Secondary Outcome

Title	Duration of Progression-free Survival (PFS)
Description	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Time Frame	CT scan or MRI if used to follow lesion for measurable disease every other cycle for first 6 months; every 6 months thereafter until disease progression for up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Enzastaurin
Arm/Group Description:	Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
Overall Number of Participants Analyzed	27
Median (90% Confidence Interval); Unit of Measure: months
	1.8; (1.5 to 2.7)

6. Secondary Outcome

Title	Prognostic Factor - Number of Patients With Platinum Sensitivity
Description	Platinum sensitive = a platinum-free interval between 6 and 12 months.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Enzastaurin
Arm/Group Description:	Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
Overall Number of Participants Analyzed	27
Measure Type: Count of Participants; Unit of Measure: Participants
Platinum Sensitive	11
Not Platinum Sensitive	16

7. Secondary Outcome

Title	Prognostic Factor - Initial 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

Eligible and treated patients

Arm/Group Title	Enzastaurin
Arm/Group Description:	Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
Overall Number of Participants Analyzed	27
Measure Type: Count of Participants; Unit of Measure: Participants
Performance Status = 0	16
Performance Status = 1	11

8. Secondary Outcome

Title	Prognostic Factor - Age at Study Entry
Description	[Not Specified]
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Enzastaurin
Arm/Group Description:	Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
Overall Number of Participants Analyzed	27
Median (Inter-Quartile Range); Unit of Measure: years
	59; (53 to 71)

Adverse Events

Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Enzastaurin
Arm/Group Description	Loading dose of Enzastaurin 375 mg TID within 30 minutes after each meal on Day 1 followed by continuous treatment with Enzastaurin 500 mg daily within 30 minutes after the same largest meal until disease progression or adverse effects prohibit further therapy. One cycle = 28 days.
All-Cause Mortality
	Enzastaurin
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Enzastaurin
	Affected / at Risk (%)
Total	12/27 (44.44%)
Gastrointestinal disorders
Obstruction, Gi - Rectum * 1	1/27 (3.70%)
Obstruction, Gi - Colon * 1	1/27 (3.70%)
Ascites * 1	1/27 (3.70%)
Dehydration * 1	1/27 (3.70%)
Constipation * 1	1/27 (3.70%)
General disorders
Death No Ctcae Term - Disease Progression Nos * 1	3/27 (11.11%)
Pain: Abdominal Pain Nos * 1	2/27 (7.41%)
Metabolism and nutrition disorders
Hyperkalemia * 1	1/27 (3.70%)
Respiratory, thoracic and mediastinal disorders
Atelectasis * 1	1/27 (3.70%)
Aspiration * 1	1/27 (3.70%)
Dyspnea * 1	1/27 (3.70%)
Vascular disorders
Thrombosis/Thrombus/Embolism * 1	1/27 (3.70%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, CTCAE (3.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Enzastaurin
	Affected / at Risk (%)
Total	27/27 (100.00%)
Blood and lymphatic system disorders
Neutrophils * 1	1/27 (3.70%)
Platelets * 1	3/27 (11.11%)
Leukocytes * 1	3/27 (11.11%)
Lymphopenia * 1	1/27 (3.70%)
Hemoglobin * 1	19/27 (70.37%)
Edema: Limb * 1	8/27 (29.63%)
Edema: Head And Neck * 1	1/27 (3.70%)
Cardiac disorders
Palpitations * 1	1/27 (3.70%)
Hypertension * 1	2/27 (7.41%)
Endocrine disorders
Hot Flashes * 1	2/27 (7.41%)
Diabetes * 1	1/27 (3.70%)
Gastrointestinal disorders
Obstruction, Gi - Colon * 1	1/27 (3.70%)
Heartburn * 1	2/27 (7.41%)
Ascites * 1	4/27 (14.81%)
Ileus * 1	1/27 (3.70%)
Dysphagia * 1	1/27 (3.70%)
Distention * 1	3/27 (11.11%)
Taste Alteration * 1	2/27 (7.41%)
Incontinence, Anal * 1	1/27 (3.70%)
Dry Mouth * 1	3/27 (11.11%)
Obstruction, Gi - Small Bowel Nos * 1	2/27 (7.41%)
Vomiting * 1	9/27 (33.33%)
Anorexia * 1	12/27 (44.44%)
Dehydration * 1	1/27 (3.70%)
Constipation * 1	12/27 (44.44%)
Nausea * 1	11/27 (40.74%)
Gastrointestinal - Other * 1	1/27 (3.70%)
Diarrhea * 1	13/27 (48.15%)
General disorders
Sweating * 1	2/27 (7.41%)
Weight Gain * 1	1/27 (3.70%)
Fever * 1	1/27 (3.70%)
Weight Loss * 1	1/27 (3.70%)
Fatigue * 1	20/27 (74.07%)
Insomnia * 1	4/27 (14.81%)
Pain: Pelvis * 1	1/27 (3.70%)
Pain: Breast * 1	1/27 (3.70%)
Pain: Chest /Thorax Nos * 1	1/27 (3.70%)
Pain: Head/Headache * 1	3/27 (11.11%)
Pain: Extremity-Limb * 1	1/27 (3.70%)
Pain: Joint * 1	3/27 (11.11%)
Pain: Bone * 1	1/27 (3.70%)
Pain: Rectum * 1	1/27 (3.70%)
Pain: Abdominal Pain Nos * 1	11/27 (40.74%)
Pain: Tumor * 1	1/27 (3.70%)
Pain: Muscle * 1	3/27 (11.11%)
Flu-Like Syndrome * 1	1/27 (3.70%)
Immune system disorders
Rhinitis * 1	4/27 (14.81%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Upper Airway Nos * 1	1/27 (3.70%)
Inf W/Nml Or Gr 1 Or 2 Anc: Pleura * 1	1/27 (3.70%)
Inf W/Nml Or Gr 1 Or 2 Anc: Blood * 1	1/27 (3.70%)
Inf W/Nml Or Gr 1 Or 2 Anc: Wound * 1	1/27 (3.70%)
Inf W/Nml Or Gr 1 Or 2 Anc: Skin(Cellulitis) * 1	1/27 (3.70%)
Inf W/Nml Or Gr 1 Or 2 Anc: Catheter-Related * 1	1/27 (3.70%)
Inf W/Nml Or Gr 1 Or 2 Anc: Colon * 1	1/27 (3.70%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos * 1	5/27 (18.52%)
Inf W/Nml Or Gr 1 Or 2 Anc: Vagina * 1	1/27 (3.70%)
Inf W/Gr 3 Or 4 Anc: Vulva * 1	1/27 (3.70%)
Metabolism and nutrition disorders
Ast * 1	2/27 (7.41%)
Gfr * 1	3/27 (11.11%)
Creatinine * 1	4/27 (14.81%)
Hypoalbuminemia * 1	5/27 (18.52%)
Alt * 1	1/27 (3.70%)
Alkaline Phosphatase * 1	3/27 (11.11%)
Hypophosphatemia * 1	2/27 (7.41%)
Hyponatremia * 1	6/27 (22.22%)
Hypertriglyceridemia * 1	1/27 (3.70%)
Hypernatremia * 1	1/27 (3.70%)
Hypocalcemia * 1	3/27 (11.11%)
Hyperkalemia * 1	3/27 (11.11%)
Hyperglycemia * 1	4/27 (14.81%)
Hypokalemia * 1	3/27 (11.11%)
Hypoglycemia * 1	1/27 (3.70%)
Hypomagnesemia * 1	4/27 (14.81%)
Nervous system disorders
Mood Alteration - Depression * 1	2/27 (7.41%)
Mood Alteration - Anxiety * 1	2/27 (7.41%)
Tremor * 1	1/27 (3.70%)
Somnolence * 1	1/27 (3.70%)
Dizziness * 1	2/27 (7.41%)
Neuropathy-Sensory * 1	1/27 (3.70%)
Neuropathy-Motor * 1	1/27 (3.70%)
Renal and urinary disorders
Renal/Genitourinary - Other * 1	1/27 (3.70%)
Urinary Color Change * 1	3/27 (11.11%)
Reproductive system and breast disorders
Vaginal Dryness * 1	1/27 (3.70%)
Respiratory, thoracic and mediastinal disorders
Pulmonary: Other * 1	1/27 (3.70%)
Cough * 1	2/27 (7.41%)
Dyspnea * 1	12/27 (44.44%)
Skin and subcutaneous tissue disorders
Hair Loss/Alopecia (Scalp Or Body) * 1	2/27 (7.41%)
Acne * 1	1/27 (3.70%)
Rash * 1	3/27 (11.11%)
Dry Skin * 1	2/27 (7.41%)
Decubitus * 1	1/27 (3.70%)
Ulceration * 1	1/27 (3.70%)
Vascular disorders
Hemorrhage, Gu - Vagina * 1	1/27 (3.70%)
Hemorrhage, Gi - Rectum * 1	1/27 (3.70%)
Hemorrhage, Gi - Upper Gi Nos * 1	1/27 (3.70%)
Hemorrhage/Pulmonary - Nose * 1	1/27 (3.70%)
Petechiae * 1	1/27 (3.70%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, CTCAE (3.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Angela Kuras on behalf of Mike Sill, PhD
• Organization: NRG Oncology
• Phone: 716-845-5702
• EMail: kurasa@nrgoncology.org

Publications of Results:

Usha L, Sill MW, Darcy KM, Benbrook DM, Hurteau JA, Michelin DP, Mannel RS, Hanjani P, De Geest K, Godwin AK. A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies. Gynecol Oncol. 2011 Jun 1;121(3):455-61. doi: 10.1016/j.ygyno.2011.02.013. Epub 2011 Mar 17.

• Responsible Party: GOG Foundation ( Gynecologic Oncology Group )
• ClinicalTrials.gov Identifier: NCT00407758
• Other Study ID Numbers: GOG-0170J; CDR0000517318; LILLY-H6Q-MC-S025
• First Submitted: December 4, 2006
• First Posted: December 5, 2006
• Results First Submitted: August 1, 2017
• Results First Posted: November 21, 2017
• Last Update Posted: March 20, 2019