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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Primary Peritoneal Cavity Cancer
• Intervention / Treatment: Drug: enzastaurin hydrochloride

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Evanston, Illinois, United States, 60201-1781
      • Evanston Northwestern Healthcare - Evanston Hospital
    • Hinsdale, Illinois, United States, 60521
      • Hinsdale Hematology Oncology Associates
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Indianapolis Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
  • Missouri
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Estabrook Cancer Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Rosenfeld Cancer Center at Abington Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center - Philadelphia
    • Reading, Pennsylvania, United States, 19612-6052
      • McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
  • Washington
    • Seattle, Washington, United States, 98195-6043
      • University Cancer Center at University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
Prognostic Factor - Number of Patients With Platinum Sensitivity	Platinum sensitive = a platinum-free interval between 6 and 12 months.	Baseline
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
Prognostic Factor - Age at Study Entry		Baseline

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Lydia Usha, MD, Rush University Medical Center; Study Chair: Jean A. Hurteau, MD, Northshore University Healthsystem

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: December 4, 2006
• First Submitted That Met QC Criteria: December 4, 2006
• First Posted (Estimate): December 5, 2006

Study Record Updates

• Last Update Posted (Actual): March 20, 2019
• Last Update Submitted That Met QC Criteria: March 8, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: recurrent ovarian epithelial cancer; primary peritoneal cavity cancer
• Other Study ID Numbers: GOG-0170J; CDR0000517318; LILLY-H6Q-MC-S025