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

Ovarian Cancer Clinical Trial

Official title:

A Phase II Evaluation of Enzastaurin (Lilly IND # 60, 933) in the Treatment of Persistent or Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00407758
• Other study ID #: GOG-0170J
• Secondary ID: CDR0000517318LIL
• Status: Completed
• Phase: Phase 2
• Start date: November 2006

Study information

• Verified date: March 2019
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Enzastaurin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well enzastaurin works in treating patients with persistent or recurrent ovarian epithelial cancer or primary peritoneal cancer.

Description:

OBJECTIVES:

Primary

• Assess the efficacy of enzastaurin hydrochloride, in terms of 6-month progression-free survival or objective tumor response, in patients with recurrent or persistent ovarian epithelial or primary peritoneal cancer.

• Determine the nature and degree of toxicity of this regimen in these patients.

Secondary

• Determine the duration of progression-free and overall survival of patients treated with this regimen.

• Determine the effects of prognostic variables, including platinum sensitivity, initial performance status, and age, in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral enzastaurin hydrochloride 3 times on day 1 and then once daily on days 2-28 of course 1. For all subsequent courses, patients receive enzastaurin hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 68 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. primary completion date: August 1, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial or primary peritoneal carcinoma

• Recurrent or persistent disease

• Measurable disease, defined as = 1 unidimensionally measurable lesion = 20 mm by conventional techniques OR = 10 mm by spiral CT scan

• Must have = 1 target lesion to assess response

• Tumors within a previously irradiated field are designated as "nontarget" lesions unless progression is documented or a biopsy is obtained to confirm persistence = 90 days after completion of radiotherapy

• Must have received 1 prior platinum-based chemotherapy regimen containing carboplatin, cisplatin, or another organoplatinum compound for management of primary disease

• Initial treatment may have included high-dose therapy, consolidation therapy, or extended therapy administered after surgical or nonsurgical assessment

• Must meet any 1 of the following criteria for platinum-based therapy:

• Disease progression during therapy

• Treatment-free interval after completion of treatment < 12 months

• Disease persistence after completion of therapy

• Ineligible for a higher priority GOG clinical trial

PATIENT CHARACTERISTICS:

• GOG performance status 0-1 (for patients who received 2 prior treatment regimens) OR 0-2 (for patients who received 1 prior treatment regimen)

• Absolute neutrophil count = 1,500/mm³

• Platelet count = 100,000/mm³

• Hemoglobin = 9 g/dL (transfusions allowed)

• Creatinine < 1.5 times upper limit of normal (ULN)

• Bilirubin = 2 times ULN

• Alkaline phosphatase = 3 times ULN (5 times ULN if liver metastases are present)

• AST and ALT = 3 times ULN (5 times ULN if liver metastases are present)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after completion of study treatment

• Able to swallow tablets

• No sensory or motor neuropathy > grade 1

• No active infection requiring antibiotics

• No other invasive malignancies or evidence of cancer within the past 5 years except nonmelanoma skin cancer

• No serious systemic disorders that would preclude study compliance, including an abnormal ECG indicative of cardiac disease

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior surgery, radiotherapy, or chemotherapy

• At least 1 week since prior anticancer hormonal therapy

• No more than 1 additional cytotoxic regimen for management of recurrent or persistent disease

• At least 4 weeks since other prior anticancer therapy, including immunotherapy

• At least 30 days since prior investigational drugs

• No prior enzastaurin hydrochloride

• No prior radiotherapy to > 25% of marrow-bearing areas

• No prior noncytotoxic therapy, including bevacizumab, for recurrent or persistent disease

• No prior treatment that would preclude treatment on this protocol

• No concurrent chemotherapy, immunotherapy, or other experimental medications

• No concurrent enzyme-inducing antiepileptic drugs, including carbamazepine, phenobarbital, or phenytoin

• No other concurrent systemic anticancer therapy

• No concurrent radiotherapy, including palliative radiotherapy

• No concurrent agents that stimulate thrombopoiesis

• No concurrent amifostine or other protective reagents

• Concurrent hormone replacement therapy allowed

• Concurrent bisphosphonates allowed provided bony metastases are present

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Peritoneal Neoplasms
• Primary Peritoneal Cavity Cancer

Intervention

Drug:
• enzastaurin hydrochloride

Locations

Country	Name	City	State
United States	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	St. Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	CCOP - Carle Cancer Center	Urbana	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 predicti — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0	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.	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.
Primary	Progression-free Survival > 6 Months Using RECIST 1.0	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.	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.
Primary	Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0	Number of participants with a maximum grade of 3 or higher during the treatment period.	Assessed every cycle while on treatment, 30 days after the last cycle of treatment
Secondary	Duration Overall Survival	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.	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.
Secondary	Duration of Progression-free Survival (PFS)	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.	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.
Secondary	Prognostic Factor - Number of Patients With Platinum Sensitivity	Platinum sensitive = a platinum-free interval between 6 and 12 months.	Baseline
Secondary	Prognostic Factor - Initial 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	Baseline
Secondary	Prognostic Factor - Age at Study Entry		Baseline