Clinical trial NCT00407758: Enzastaurin in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer or Primary Peritoneal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Primary Peritoneal Cavity Cancer
Keywords: recurrent ovarian epithelial cancer
primary peritoneal cavity cancer
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-12-05
Enrollment: 28
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0
timeFrame: 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.
measure: Progression-free Survival > 6 Months Using RECIST 1.0
timeFrame: 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.
measure: Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
timeFrame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment
Secondary outcomes:
measure: Duration Overall Survival
timeFrame: 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.
measure: Duration of Progression-free Survival (PFS)
timeFrame: 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.
measure: Prognostic Factor - Number of Patients With Platinum Sensitivity
timeFrame: Baseline
measure: Prognostic Factor - Initial Performance Status
timeFrame: Baseline
measure: Prognostic Factor - Age at Study Entry
timeFrame: Baseline
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare - Evanston Hospital
state: Illinois
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Indianapolis Hospital
state: Indiana
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Abington
country: United States
facility: Rosenfeld Cancer Center at Abington Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
Study officials:
affiliation: Rush University Medical Center
name: Lydia Usha, MD
role: STUDY_CHAIR
affiliation: Endeavor Health
name: Jean A. Hurteau, MD
role: STUDY_CHAIR
References:
citation: 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.