Trastuzumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

A Phase II Evaluation of Trastuzumab (MoAb HER2) in Patients With Advanced, Recurrent or Persistent Endometrial Carcinoma With or Without Prior Chemotherapy

Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Phase II trial to study the effectiveness of trastuzumab in treating patients who have stage III, stage IV, or recurrent endometrial cancer.

Study Overview

• Status: Completed
• Conditions: Recurrent Uterine Corpus Carcinoma; Endometrial Adenocarcinoma; Stage III Uterine Corpus Cancer AJCC v7; Stage IV Uterine Corpus Cancer AJCC v7; ERBB2 Gene Amplification
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Trastuzumab

Detailed Description

PRIMARY OOBJECTIVES:

I. Determine the antitumor activity of trastuzumab (Herceptin), in terms of response, in patients with advanced, recurrent, or persistent endometrial adenocarcinoma that demonstrates HER2/neu gene amplification by fluorescent in situ hybridization.

II. Determine the toxicity of this regimen in these patients.

SECONDARY OBJECTIVES:

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

II. Determine the effects of prognostic factors (i.e., initial performance status and histological grade) in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study.

Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 25-42 patients will be accrued for this study within 12 years.

• Study Type: Interventional
• Enrollment (Actual): 34
• 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: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed endometrial adenocarcinoma

  • Advanced, recurrent, or persistent disease
  • Refractory to curative therapy
• HER2/neu gene amplification by fluorescent in situ hybridization

• Measurable disease

  • Previously irradiated field as sole site of measurable disease allowed if evidence of progression since completion of radiotherapy
• Performance status - GOG 0-2
• Absolute neutrophil count ? 1,500/mm^3
• Platelet count ? 100,000/mm^3
• Bilirubin ? 1.5 times upper limit of normal (ULN)
• Creatinine ? 1.5 times ULN
• LVEF ? 45% by echocardiogram or MUGA
• History of coronary artery disease and/or congestive heart failure allowed if medical management of condition has been stable within the past 6 months
• No active or unstable cardiac disease
• No active angina
• No myocardial infarction within the past 6 months
• No requirement for supplemental oxygen at rest or with ambulation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection requiring antibiotics
• No uncontrolled infection
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
• No other unstable medical condition that would preclude study participation
• At least 3 weeks since prior biologic and immunologic agents directed at the malignant tumor
• No prior anti-HER2 monoclonal antibody preparation
• No other concurrent immunotherapy
• Recovered from prior chemotherapy
• Multiple prior chemotherapy regimens allowed
• No more than 320 mg/m^2 total dose of prior doxorubicin allowed (including doxorubicin HCl liposome or other liposomally encapsulated doxorubicin preparations)
• No concurrent chemotherapy
• At least 1 week since prior hormonal therapy directed at the malignant tumor

• No concurrent hormonal therapy

  • Continuation of hormone replacement therapy allowed
• See Disease Characteristics
• At least 3 weeks since prior radiotherapy for the malignant tumor and recovered
• No concurrent radiotherapy
• Recovered from prior recent surgery
• At least 3 weeks since any prior therapy directed at the malignant tumor
• No prior cancer treatment that would contraindicate study therapy

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 (trastuzumab); Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Trastuzumab; Given IV; Other Names: Herceptin; ABP 980; ALT02; Anti-c-ERB-2; Anti-c-erbB2 Monoclonal Antibody; Anti-ERB-2; Anti-erbB-2; Anti-erbB2 Monoclonal Antibody; Anti-HER2/c-erbB2 Monoclonal Antibody; Anti-p185-HER2; c-erb-2 Monoclonal Antibody; HER2 Monoclonal Antibody; Herceptin Biosimilar PF-05280014; Herceptin Trastuzumab Biosimilar PF-05280014; Herzuma; MoAb HER2; Monoclonal Antibody c-erb-2; Monoclonal Antibody HER2; Ogivri; Ontruzant; PF-05280014; rhuMAb HER2; RO0452317; Trastuzumab Biosimilar ABP 980; Trastuzumab Biosimilar ALT02; trastuzumab biosimilar EG12014; Trastuzumab Biosimilar HLX02; Trastuzumab Biosimilar PF-05280014; Trastuzumab-dkst; Trastuzumab-pkrb; Trastuzumab-QYYP; Trazimera; Trastuzumab-DTTB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency and duration of objective response	Up to 5 years
Frequency and severity of observed adverse effects assessed using Common Terminology Criteria (CTC) version 2.0	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of progression-free survival	Will be evaluated with non-parametric statistics (such as the log-rank test) through comparisons with the historical controls.	From study entry until disease progression, death or date or last contact, assessed up to 5 years
Duration of overall survival	Will be evaluated with non-parametric statistics (such as the log-rank test) through comparisons with the historical controls.	From study entry to death or date or last contact, assessed up to 5 years
Prognostic factors (i.e., initial performance status and histological grade)	Comparisons will be made through a Cox model, which allows for adjustments with the prognostic variables.	Not Provided

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Gynecologic Oncology Group
• Investigators: Principal Investigator: Gini F Fleming, Gynecologic Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2000
• Primary Completion (Actual): September 4, 2007
• Study Completion (Actual): January 31, 2010

Study Registration Dates

• First Submitted: August 3, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 30, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Carcinoma; Recurrence; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Trastuzumab; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Trastuzumab biosimilar HLX02
• Other Study ID Numbers: NCI-2012-02356 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA027469 (U.S. NIH Grant/Contract); CDR0000068091; GOG-0181B (Other Identifier: CTEP); GOG-0181-B (Other Identifier: Gynecologic Oncology Group)