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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00407758

Enrollment

Registered

2006-12-05

Start date

2006-11-30

Completion date

Unknown

Last updated

2019-03-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ovarian Cancer, Primary Peritoneal Cavity Cancer

Keywords

recurrent ovarian epithelial cancer, primary peritoneal cavity cancer

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.

Interventions

DRUGenzastaurin hydrochloride

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 120 Years

Healthy volunteers

Inclusion 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

Design outcomes

Primary

Measure	Time frame	Description
Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0	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.	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.
Progression-free Survival > 6 Months Using RECIST 1.0	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.	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.
Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0	Assessed every cycle while on treatment, 30 days after the last cycle of treatment	Number of participants with a maximum grade of 3 or higher during the treatment period.

Secondary

Measure	Time frame	Description
Prognostic Factor - Initial 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
Duration Overall Survival	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.	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Prognostic Factor - Age at Study Entry	Baseline	—
Duration of Progression-free Survival (PFS)	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.	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.
Prognostic Factor - Number of Patients With Platinum Sensitivity	Baseline	Platinum sensitive = a platinum-free interval between 6 and 12 months.

Countries

United States

Participant flow

Recruitment details

This trial was opened to patient entry on November 6, 2006 and was closed to accrual on May 7, 2007.

Participants by arm

Arm	Count
Enzastaurin 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.	27
Total	27

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	ineligible -improper prior treatment	1

Baseline characteristics

Characteristic	Enzastaurin
Age, Customized 40-49 years	4 Participants
Age, Customized 50-59 years	10 Participants
Age, Customized 60-69 years	6 Participants
Age, Customized 70-79 years	7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	26 Participants
Sex: Female, Male Female	27 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	27 / 27
serious Total, serious adverse events	12 / 27

Outcome results

Primary