Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

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Trial phase: 
Phase I
Recruitment status: 
Recruiting

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Internal radiation therapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Giving cetuximab together with cisplatin and radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of cetuximab when given together with cisplatin and radiation therapy in treating patients with stage IB, stage II, stage III, or stage IVA cervical cancer.

Background information
Trial ID: 
NCT00104910
Other unique IDs: 
CDR0000413880
GOG-9918
Official title: 

A Phase I Trial of Tailored Radiation Therapy With Concomitant Cetuximab (C225, NSC #714692) and Cisplatin (NSC #119875) in the Treatment of Patients With Cervical Cancer

Detailed description: 

OBJECTIVES: Primary

  • Determine the maximum tolerated dose or safe biologically effective dose of cetuximab when administered in combination with cisplatin, external beam radiotherapy, and brachytherapy in patients with stage IB-IVA cervical cancer.
  • Determine the feasibility of this regimen, in terms of chronic and acute toxic effects, in these patients.

Secondary

  • Determine the distribution of progression-free survival and overall survival of patients treated with this regimen at 1 year after study entry.
  • Determine the site of recurrence (locoregional vs distant) in patients treated with this regimen up to 1 year after study entry.
  • Correlate response or progression-free survival with epidermal growth factor receptor expression in tumor samples from patients treated with this regimen at 1 year after study entry.
  • Correlate response or progression-free survival with grade of cetuximab-induced rash in patients treated with this regimen at 1 year after study entry.

OUTLINE: This is a multicenter, dose-escalation study of cetuximab. Patients are stratified according to nodal status (positive para-aortic and/or pelvic lymph nodes vs negative para-aortic and pelvic lymph nodes). Patients receive cetuximab IV over 1-2 hours and cisplatin IV on days 1, 8, 15, 22, 29, and 36 (weeks 1-6). Patients also undergo external beam radiotherapy to the para-aortic and pelvic lymph nodes OR whole pelvis once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33 (weeks 1-5). Patients then receive either 1 or 2 applications of low-dose rate brachytherapy in weeks 6-8 OR 5 applications of high-dose rate (HDR)* brachytherapy once weekly in weeks 4-8. Treatment continues in the absence of disease progression or unacceptable toxicity. NOTE: *No external beam radiotherapy is administered on the day of HDR brachytherapy. If the majority of external beam radiotherapy has been administered, HDR brachytherapy may be administered in 2 applications per week (separated by at least 72 hours) in order to complete all treatment within 8 weeks. Cohorts of 3-6 patients per stratum receive escalating doses of cetuximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 3 months for 1 year. PROJECTED ACCRUAL: Approximately 30-100 patients will be accrued for this study.

Number to be enrolled: 
100 patients
Clinical information
Age groups: 
Adult
Senior
Gender: 
Female
Eligibility criteria: 

DISEASE CHARACTERISTICS:

  • Histologically confirmed cervical cancer
    • Clinical stage IB-IVA disease
    • Any cell type allowed
  • Positive or negative pelvic and/or para-aortic lymph nodes by radiography
  • Unstained sections from primary tumor available

PATIENT CHARACTERISTICS: Age

  • 18 and over

Performance status

  • GOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN

Renal

  • Creatinine normal OR
  • Creatinine clearance > 50 mL/min
  • Patients with ureteral obstruction must undergo stent or nephrostomy tube placement prior to study entry
  • No renal abnormality (e.g., pelvic kidney or horseshoe kidney) that would require modification of radiation fields

Cardiovascular

  • No significant cardiac disease within the past 6 months, including any of the following:
    • Uncontrolled hypertension
    • Unstable angina
    • Congestive heart failure
    • Uncontrolled arrhythmia

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No sensory or motor neuropathy > grade 1
  • No septicemia
  • No severe infection
  • No circumstance that would preclude study participation or follow-up
  • No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
  • No uncontrolled seizure disorder
  • No active neurologic disease
  • No history of active collagen vascular disease

PRIOR CONCURRENT THERAPY: Biologic therapy

  • No prior chimerized or murine monoclonal antibody therapy

Chemotherapy

  • No prior cytotoxic chemotherapy for cervical cancer

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior pelvic or abdominal radiotherapy for cervical cancer
  • No concurrent intensity modulated radiotherapy

Surgery

  • No prior renal transplantation
  • More than 30 days since prior major surgery (excluding diagnostic biopsy)

Other

  • No other prior therapy for cervical cancer
  • No prior cancer treatment that would preclude study therapy
  • No other concurrent investigational agents

Study design: 
Treatment
Interventions: 
radiation therapy
cisplatin
brachytherapy
Cetuximab
Conditions treated: 
Cervical Cancer
Outcome measurements: 

Maximum tolerated dose as assessed by ADEERS every 4 weeks [ Designated as safety issue: Yes ]

Safety as assessed by ADEERS every 4 weeks [ Designated as safety issue: Yes ]

Feasibility as assessed by ADEERS every 4 weeks [ Designated as safety issue: No ]

Progression-free survival and overall survival at 1 year after study entry [ Designated as safety issue: No ]

Site of recurrence, loco-regional vs distant as assessed by clinical and radiologic evaluationup to 1 year after study entry [ Designated as safety issue: No ]

Correlate response or progression-free survival with epidermal growth factor (EGF) receptor expression as assessed by immunohistochemistry at 1 year after study entry [ Designated as safety issue: No ]

Correlate response or progression-free survival with grade of cetuximab-induced rash as assessed by GOG toxicity reporting at 1 year after study entry [ Designated as safety issue: Yes ]

Funding
Funding types: 
NIH
NETWORK
Sponsor: 
National Cancer Institute (NCI)
Gynecologic Oncology Group
Dates
Date the data was first received: 
Thu, 2005-03-03
Trial start date: 
Fri, 2005-04-01
Trial completion date: 
Wed, 1969-12-31
Trial last updated: 
Wed, 2009-05-20