Topotecan, Cisplatin and Bevacizumab for Recurrent/Persistent Cervical Cancer

NCT00548418 | Completed Phase 2 Results DMC

• 2 other identifiers: 06-1098 / 201110266GSK 107278
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

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

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Anti-tumor Activity as Measured by Surviving Progression-free

  Defined as the period from study entry until documentation of disease progression, death, or date of last contact, whichever occurred first.

  Progression-free survival at 6 months

Secondary Outcomes (4)

• Overall Survival

  Until death (follow-up ranged from 1.7 months to 33.4 months)

• Frequency of Response as Measured by RECIST Criteria (Imaging)

  Tumor response measured prior to every other cycle of therapy (range of follow-up to measure overall response was 1.6-9.5 months)

• Correlate Patterns of Gene Expression as Assessed by Microarrays

  Correlative studies when specimens available

• Correlate Hypoxia Inducible Factor 1 (HIF-1) and Hypoxia Induced Gene Expression as Measured by Laboratory Studies

  When specimens available

Study Arms (1)

I

EXPERIMENTAL

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; Drug: Cisplatin; Drug: Bevacizumab

Interventions

Topotecan DRUG

Also known as: Hycamtin

I

Cisplatin DRUG

Also known as: CDDP, Platin

I

Bevacizumab DRUG

Also known as: Avastin

I

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• GlaxoSmithKline: collaborator
• Genentech, Inc.: collaborator

Study Sites (3)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Duke Cancer Institute

Durham, North Carolina, United States

Location

The Ohio State University College of Medicine

Columbus, Ohio, United States

Location

Related Publications (1)

• 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.

  PMID: 23591400 DERIVED

Related Links

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

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Topotecan; Cisplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: David G. Mutch, M.D.
• Organization: Washington University School of Medicine

mutchd@wudosis.wustl.edu

314-362-2181

Study Officials

• David G Mutch, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2007
• First Posted: October 24, 2007
• Study Start: February 1, 2007
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 1, 2014
• Results First Posted: July 28, 2014

Record last verified: 2014-07

Locations

US (3)