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

A Phase II Evaluation of Bortezomib (Velcade™, PS-341, NSC #681239, IND #58443) in the Treatment of Persistent or Recurrent Platinum-Sensitive Epithelial Ovarian or Primary Peritoneal Cancer

Phase II trial to study the effectiveness of bortezomib in treating patients who have persistent or recurrent ovarian epithelial cancer or primary peritoneal cancer. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

Study Overview

• Status: Completed
• Conditions: Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: bortezomib

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the antitumor activity of bortezomib in patients with persistent or recurrent platinum-sensitive ovarian epithelial or primary peritoneal carcinoma.

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

OUTLINE: This is a multicenter study.

Patients receive bortezomib IV twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Gynecologic Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed persistent or recurrent ovarian epithelial or primary peritoneal carcinoma

• Measurable disease

  • At least 20 mm by conventional techniques (e.g., palpation, x-ray, plain CT scan, or MRI) OR at least 10 mm by spiral CT scan

• Must have had prior therapy with no more than 1 platinum-based chemotherapy regimen for primary disease (e.g., carboplatin, cisplatin, or other organoplatinum compound)

  • A second regimen containing paclitaxel allowed provided patient received no prior paclitaxel therapy

• Platinum-sensitive disease

  • Treatment-free interval without progressive disease for more than 6 months but less than 12 months after therapy with platinum-based regimen
• At least 1 target lesion outside previously irradiated field
• Ineligible for higher priority GOG protocol
• Performance status - GOG 0-2 (if received 1 prior therapy regimen)
• Performance status - GOG 0-1 (if received 2 prior therapy regimens)
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN
• Creatinine no greater than 1.5 times ULN
• No evidence of acute ischemia or significant conduction abnormality (e.g., left anterior hemiblock in the presence of right bundle branch block or second or third degree atrioventricular block) on electrocardiogram
• No myocardial infarction within the past 6 months
• No cerebrovascular event or transient ischemic attack within the past 6 months
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection requiring antibiotics
• No other invasive malignancy within the past 5 years except non-melanoma skin cancer
• No sensory or motor neuropathy greater than grade 1
• No more than 1 prior non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule inhibitors of signal transduction) for recurrent or persistent disease
• At least 4 weeks since prior biological or immunological agents and recovered
• No prior cytotoxic chemotherapy for recurrent or persistent disease, including retreatment with initial chemotherapy regimen
• At least 4 weeks since prior chemotherapy and recovered
• At least 1 week since prior anti-cancer hormonal therapy and recovered
• Concurrent hormone replacement therapy allowed
• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to target lesions
• No prior radiotherapy to more than 25% of marrow-bearing areas
• At least 4 weeks since prior surgery and recovered
• No prior bortezomib
• No prior anti-cancer therapy that would preclude study treatment
• No concurrent amifostine or other protective agents

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (bortezomib); Patients receive bortezomib IV twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: bortezomib; Given IV; Other Names: MLN341; LDP 341; VELCADE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response Duration	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. Complete and partial responses are included in the objective tumor response rate.	From study entry, up to 5 years
Frequency and Severity of Observed Adverse Events		Up to 5 years
Objective Partial/Complete Tumor Response Based on the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) Criteria	Number of participants who experienced an objective tumor response up to 5 years. Per RECIST version 1.0 criteria: each target lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or >= 10 mm when measured by spiral CT. Complete Response is a disappearance of all target and non-target lesions. Partial Response is 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.	From study entry until disease progression/intolerable toxicity/study withdrawal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		From study entry, up to 5 years following disease progression
Progression-Free Survival	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.	From study entry up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Gynecologic Oncology Group
• Investigators: Principal Investigator: Carol Aghajanian, Gynecologic Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2001
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: September 13, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Recurrence; Carcinoma, Ovarian Epithelial; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: NCI-2012-02404 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA027469 (U.S. NIH Grant/Contract); CDR0000068853; GOG-0146N (Other Identifier: CTEP); GOG #0146N (Other Identifier: Gynecologic Oncology Group)