A Phase I/II Study of Cisplatin and Radiation in Combination With Sorafenib in Cervical Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by University Health Network, Toronto.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Bayer
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00510250
First received: July 31, 2007
Last updated: October 6, 2011
Last verified: October 2011
  Purpose

This will be a multi-institution, single-arm, open-label, phase I/II trial. Eligible patients will have pathologically-proven T1b-3b, N0/1, M0 epithelial carcinoma of the cervix. We hypothesize that sorafenib in combination with chemotherapy and radiotherapy may have anti-tumor activity in patients with cervical cancer. Sorafenib has not previously been combined with conventional RT-CT to treat cervix cancer.


Condition Intervention Phase
Cancer of the Cervix
Drug: Sorafenib
Drug: Cisplatin
Procedure: Radiation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Cisplatin and Radiation in Combination With Sorafenib in Cervical Cancer

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Determine the biologic activity of sorafenib in cervix cancer. [ Time Frame: Not Determined ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the acute and late toxicity, and effect of sorafenib in combination with radiation and chemotherapy on the disease-free survival of patients with high-risk cervix cancer. [ Time Frame: Not Determined ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: June 2007
Estimated Study Completion Date: April 2012
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Sorafenib
    200mg PO BID x 7 days prior to Radiation and Cisplatin for Low-Risk Patients or 200mg PO BID x 7 days prior to, and 35 days during Radiation and Cisplatin for High-Risk Patients
    Drug: Cisplatin
    40mg/m2 administered weekly via IV, with Radiation
    Procedure: Radiation
    Administered for 30-40 days.Combination of external beam radiotherapy followed by intra-cavitary brachytherapy.
Detailed Description:

During the phase I component of the study, low risk patients (tumor size ≤5 cm and radiographically node negative) will receive sorafenib alone in escalating doses for at least 1 week prior to the start of conventional treatment with radiotherapy and chemotherapy (RT-CT). High risk patients (tumor > 5 cm or node positive) will receive sorafenib alone in escalating dose for at least 1 week prior to the start of RT-CT, as well as concurrently with RT-CT. Cohorts of 3 patients per dose level are planned. If 1/3 patients encounters a dose-limiting toxicity (DLT), then that cohort will be expanded to 6 patients. If >2/3 of patients encounter a DLT, then that dose level will be declared as the maximum tolerated dose (MTD). An additional 3 patients will be entered into the dose level one below the MTD. The recommended phase II dose (RPTD) is defined as the dose level with < 1/6 patients with DLT.

For the phase II component, all patients will receive sorafenib at the RPTD for at least 1 week prior to, and concurrent with, RT-CT.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have biopsy-proven epithelial carcinoma of the cervix, T1B-3B, N0/1, M0 with visible or palpable disease and a decision to treat radically with radiotherapy and concurrent cisplatin chemotherapy (RT-CT).
  • ECOG performance status 0, 1 or 2 (Karnofsky>=60%)
  • Life expectancy of greater than 12 weeks.
  • Patients must have normal organ and marrow function as defined below:

    • Leukocytes >3,000/mcL
    • Absolute neutrophil count >1,500/mcL
    • Platelets >100,000/mcL
    • Hemoglobin > 9 g/dL
    • Total bilirubin Within normal institutional limits
    • AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of normal
    • Creatinine Within normal institutional limits, or
    • Creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above normal
  • No prior treatment for cervix cancer.
  • The effects of sorafenib on the developing human fetus at the recommended therapeutic dose are unknown. Although radical RT-CT for cervix cancer is not compatible with survival of a developing fetus, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • No active malignancy at another site.
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients may not be receiving any other investigational agents concurrently or within 4 weeks. Patients who have previous exposure to a raf-kinase inhibitor are excluded
  • Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher, or diastolic blood pressure of 90 mmHg or higher) are ineligible.
  • Patients with any condition that impairs their ability to swallow sorafenib tablets are excluded (e.g. gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease).
  • Bleeding disorders. Patients cannot be receiving therapeutic anticoagulation. Prophylactic anticoagulation (ie. low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for PT, INR, or PTT are met.
  • Patients with known brain metastases should be excluded because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. These patients would not be eligible for radical RT-CT for cervix cancer, but instead would be treated for palliation.
  • Patients with intercurrent cardiac dysfunction including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia are excluded as are those with a history of ischemic heart disease including myocardial infarction.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because sorafenib has the potential for teratogenic or abortifacient effects as shown by the gross fetal malformations and effects on embryo-fetal survival seen in reproductive toxicity studies in the rat. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sorafenib, breastfeeding should be discontinued if the mother is treated with sorafenib.
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with sorafenib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  • A decision to treat with extended-field pelvic and para-aortic radiotherapy, specifically cases where the para-aortic field will extend cranial to the L3-4 vertebral inter-space.
  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: NCT00510250

Locations
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
Bayer
Investigators
Principal Investigator: Amit Oza, MD FRCP Princess Margaret Hospital, Canada
Principal Investigator: Michael Milosevic, MD FRCPC Princess Margaret Hospital, Canada
  More Information

No publications provided

Responsible Party: Dr. Amit Oza, Princess Margaret Hospital, University Health Network
ClinicalTrials.gov Identifier: NCT00510250     History of Changes
Other Study ID Numbers: DDPDRO-002, Bayer Protocol# 12138
Study First Received: July 31, 2007
Last Updated: October 6, 2011
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Cervix Cancer
Cervical Cancer
Sorafenib
Cisplatin
Radiation
Radiotherapy
Phase I
Phase II
Carcinoma
Cancer
Cervix

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
Cisplatin
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014