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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


Phase 1
18 Years
N/A
Open (Enrolling)
Female
Cervical Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose as assessed by ADEERS every 4 weeks

Safety Issue:

Yes

Principal Investigator

John H. Farley, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Uniformed Services University of the Health Sciences

Authority:

United States: Federal Government

Study ID:

CDR0000413880

NCT ID:

NCT00104910

Start Date:

April 2005

Completion Date:

Related Keywords:

  • Cervical Cancer
  • cervical adenocarcinoma
  • cervical adenosquamous cell carcinoma
  • cervical squamous cell carcinoma
  • cervical small cell carcinoma
  • stage IB cervical cancer
  • stage IIA cervical cancer
  • stage IIB cervical cancer
  • stage III cervical cancer
  • stage IVA cervical cancer
  • Uterine Cervical Neoplasms

Name

Location

University of Chicago Cancer Research CenterChicago, Illinois  60637
MetroHealth Cancer Care Center at MetroHealth Medical CenterCleveland, Ohio  44109
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Women and Infants Hospital of Rhode IslandProvidence, Rhode Island  02905
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Riverside Methodist Hospital Cancer CareColumbus, Ohio  43214
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104