Topotecan, Cisplatin and Bevacizumab for Recurrent/Persistent Cervical Cancer

NCT ID: NCT00548418

Last Updated: 2014-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2012-12-31

Brief Summary

The purpose of this study is to determine whether the combination of topotecan, cisplatin and bevacizumab is effective in the treatment of recurrent or persistent cervical cancer

Detailed Description

Cervical cancer remains a major cause of morbidity and mortality in women. Chemoradiation has led to improvements in survival, but the prognosis for patients with recurrent, metastatic cervical cancer remains poor. There is the need for more effective treatments for the management of recurrent/persistent cervical cancer. Angiogenesis appears to play an important role in cervical cancer development and progression, therefore VEGF inhibition appears to be a rationale therapeutic strategy for cervical cancer. There is increasing evidence that combining an anti-angiogenic agent with either cytotoxic chemotherapy or radiation enhances anti-tumor activity. This study combines the current most active chemotheraputic regimen for cervical cancer (cisplatin + topotecan) with an anti-angiogenic agent.

Conditions

Cervical Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

I

Cisplatin 50 mg/m2 IV day 1 of a 21 day cycle

Topotecan 0.75 mg/m2 IV Days 1, 2, 3 of a 21 day cycle

Bevacizumab 15 mg/kg day 1 of a 21 day cycle

Group Type: EXPERIMENTAL

Topotecan

Intervention Type: DRUG

Cisplatin

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Interventions

Topotecan

Intervention Type: DRUG

Cisplatin

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Other Intervention Names

Hycamtin; CDDP; Platin; Avastin

Eligibility Criteria

Inclusion Criteria

• Recurrent or persistent squamous, adenosquamous or adenocarcinoma of the uterine cervix not amenable to curative treatment with surgery and/or radiotherapy
• No prior therapy (radiation, chemotherapy, hormonal therapy or immunotherapy) for recurrence or persistence. May have received platinum in combination with radiation as part of up-front treatment or adjuvant treatment
• Must have measurable disease as defined by RECIST criteria
• Must have at least one "target lesion" to assess response
• Performance status of 0 or 1
• Patients with ureteral obstruction must undergo stent or nephrostomy tube placement prior to study entry
• At least 4 weeks must have elapsed since prior treatment
• Age >= 18 years
• Patients of childbearing potential must have a negative pregnancy test, use effective means of contraception
• Signed informed consent
• Bone marrow function: ANC >= 1500/ul; platelets >= 100,000 /ul
• Renal function: creatinine <= 1,5 X ULN (if > 1.5 creatinine clearance must be > 60 ml/min)
• Hepatic function: bilirubin <= 1.5 X ULN, AST and alkaline phosphatase <= 2.5 X ULN
• Neurologic function: neuropathy < CTC grade 1
• Coagulation: PT INR <= 1.5

Exclusion Criteria

• Evidence of sepsis or severe infection
• Prior therapy for recurrence
• Patients with serious, non-healing wound, ulcer or bone fracture
• Patients with history or evidence of nervous system disease, including primary brain tumor, brain metastases, seizure not controlled with standard medical therapy, CVA, stroke, TIA or subarachnoid hemorrhage within 6 months of 1st date of treatment on study
• Patients with history of other invasive malignancy (treatment within last 5 years) other than non-melanoma skin cancer
• Patient with clinically significant cardiovascular disease defined as:
• Inadequately controlled hypertension (systolic > 150 and/or diastolic > 100 on antihypertensive medications); prior history of hypertensive crisis or hypertensive encephalopathy
• Unstable angina within 6 months of enrollment
• NYHA Grade II or greater congestive heart failure
• Serious cardiac arrythmia requiring medication
• Grade 2 or greater peripheral vascular disease; claudication within 6 months
• History of myocardial infarction within 6 months
• Previously diagnosed coagulopathy, disseminated intravascular coagulopathy, immune thrombocytopenia purpura, thrombotic thrombocytopenia purpura or tumor involving major vessels
• Significant vascular disease: aortic aneurysm, aortic dissection
• Active thromboembolic disease: pulmonary embolism, deep venous thrombosis
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1 of study; anticipation of need for major surgical procedure during course of the study
• Minor surgical procedure other than central venous access placement, within 7 days prior to day 1 of study
• Patients with proteinuria - patients with urine protein of 1+ on dipstick or >=30 mg/dl at baseline should undergo UPCR; patients with UPCR of >=1.0 should be excluded
• Patients who are pregnant or lactating
• No prior investigational agent within 30 days or planned participation in an experimental drug study
• Patients whose circumstances do not permit completion of study or required follow-up
• Prior therapy with bevacizumab or topotecan. Prior platinum therapy allowed as part of initial treatment
• History of abdominal fistula, GI perforation or intra-abdominal abscess within 6 months prior to study enrollment.
• Known hypersensitivity to any component of bevacizumab

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David G Mutch, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Duke Cancer Institute

Durham, North Carolina, United States

The Ohio State University College of Medicine

Columbus, Ohio, United States

Countries

United States

References

Zighelboim I, Wright JD, Gao F, Case AS, Massad LS, Mutch DG, Powell MA, Thaker PH, Eisenhauer EL, Cohn DE, Valea FA, Alvarez Secord A, Lippmann LT, Dehdashti F, Rader JS. Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer. Gynecol Oncol. 2013 Jul;130(1):64-8. doi: 10.1016/j.ygyno.2013.04.009. Epub 2013 Apr 13.

Reference Type: DERIVED

PMID: 23591400 (View on PubMed)

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

GSK 107278

Identifier Type: -

Identifier Source: secondary_id

06-1098 / 201110266

Identifier Type: -

Identifier Source: org_study_id