Topotecan, Cisplatin and Bevacizumab for Recurrent/Persistent Cervical Cancer

This study has been completed.
Sponsor:
Collaborators:
GlaxoSmithKline
Genentech, Inc.
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00548418
First received: October 23, 2007
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Cervical Cancer
Drug: Topotecan
Drug: Cisplatin
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Topotecan, Cisplatin and Bevacizumab for Recurrent/Persistent Cervical Cancer

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Anti-tumor Activity as Measured by Surviving Progression-free [ Time Frame: Progression-free survival at 6 months ] [ Designated as safety issue: No ]
    Defined as the period from study entry until documentation of disease progression, death, or date of last contact, whichever occurred first.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Until death (follow-up ranged from 1.7 months to 33.4 months) ] [ Designated as safety issue: No ]
    Defined as time from study entry until death from any cause or date of last contaqct.

  • Frequency of Response as Measured by RECIST Criteria (Imaging) [ Time Frame: Tumor response measured prior to every other cycle of therapy (range of follow-up to measure overall response was 1.6-9.5 months) ] [ Designated as safety issue: No ]

    RECIST criteria:

    Complete response is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart.

    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.

    Progression is defined as ANY of the following - 20% increase in the sum of LD target lesions, 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, progression of existing non-target lesions

    Stable disease is any condition not meeting the above criteria


  • Correlate Patterns of Gene Expression as Assessed by Microarrays [ Time Frame: Correlative studies when specimens available ] [ Designated as safety issue: No ]
  • Correlate Hypoxia Inducible Factor 1 (HIF-1) and Hypoxia Induced Gene Expression as Measured by Laboratory Studies [ Time Frame: When specimens available ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: February 2007
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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

Drug: Topotecan
Other Name: Hycamtin
Drug: Cisplatin
Other Names:
  • CDDP
  • Platin
Drug: Bevacizumab
Other Name: Avastin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548418

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, North Carolina
Duke Cancer Institute
Durham, North Carolina, United States
United States, Ohio
The Ohio State University College of Medicine
Columbus, Ohio, United States
Sponsors and Collaborators
Washington University School of Medicine
GlaxoSmithKline
Genentech, Inc.
Investigators
Principal Investigator: David G Mutch, M.D. Washington University Early Recognition Center
  More Information

Additional Information:
No publications provided by Washington University School of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00548418     History of Changes
Other Study ID Numbers: 06-1098 / 201110266, GSK 107278
Study First Received: October 23, 2007
Results First Received: June 27, 2014
Last Updated: July 28, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Bevacizumab
Cisplatin
Topotecan
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 29, 2014