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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT00104910
First received: March 3, 2005
Last updated: December 12, 2013
Last verified: December 2013
  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. 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.


Condition Intervention Phase
Cervical Adenocarcinoma
Cervical Adenosquamous Cell Carcinoma
Cervical Small Cell Carcinoma
Cervical Squamous Cell Carcinoma
Stage IB Cervical Cancer
Stage IIA Cervical Cancer
Stage IIB Cervical Cancer
Stage III Cervical Cancer
Stage IVA Cervical Cancer
Radiation: brachytherapy
Radiation: 3-dimensional conformal radiation therapy
Biological: cetuximab
Drug: cisplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) or biologically effective dose (BED) of Cetuximab in combination with cisplatin and extended field radiation or whole pelvis radiation, graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Evaluation of the regimens will be conducted separately by the type of radiation received (extended field radiation or whole pelvis radiation).

  • Incidence of toxicities at the MTD, assessed by CTCAE v3.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: From study entry until disease progression, death or date of last contact, up to 1 year ] [ Designated as safety issue: No ]
  • Site of recurrence, loco-regional vs distant, assessed by clinical and radiological evaluation [ Time Frame: From study entry until disease progression, death or date of last contact, up to 1 year ] [ Designated as safety issue: No ]
  • Frequency of chronic toxicities, assessed by CTCAE v3.0 [ Time Frame: From study entry until disease progression, death or date of last contact, up to 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: January 2005
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (brachytherapy, radiation, cetuximab, cisplatin)
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.
Radiation: brachytherapy
Other Names:
  • low-LET implant therapy
  • radiation brachytherapy
  • therapy, low-LET implant
Radiation: 3-dimensional conformal radiation therapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP

Detailed Description:

PRIMARY OBJECTIVES:

I. 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.

II. Determine the feasibility of this regimen, in terms of chronic and acute toxic effects, in these patients.

SECONDARY OBJECTIVES:

I. Determine the distribution of progression-free survival and overall survival of patients treated with this regimen at 1 year after study entry.

II. Determine the site of recurrence (locoregional vs distant) in patients treated with this regimen up to 1 year after study entry.

III. 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.

IV. 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.

  Eligibility

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

Inclusion Criteria:

  • 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
  • Performance status - GOG 0-1
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Creatinine normal
  • 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
  • No significant cardiac disease within the past 6 months, including any of the following:

    • Uncontrolled hypertension
    • Unstable angina
    • Congestive heart failure
    • Uncontrolled arrhythmia
  • 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
  • No prior chimerized or murine monoclonal antibody therapy
  • No prior cytotoxic chemotherapy for cervical cancer
  • No prior pelvic or abdominal radiotherapy for cervical cancer
  • No concurrent intensity modulated radiotherapy
  • No prior renal transplantation
  • More than 30 days since prior major surgery (excluding diagnostic biopsy)
  • No other prior therapy for cervical cancer
  • No prior cancer treatment that would preclude study therapy
  • No other concurrent investigational agents
  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: NCT00104910

Locations
United States, Georgia
Georgia Regents University
Augusta, Georgia, United States, 30912
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
United States, New Jersey
Cooper Hospital University Medical Center
Camden, New Jersey, United States, 08103
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
Lake University Ireland Cancer Center
Mentor, Ohio, United States, 44060
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Rhode Island
Women and Infants Hospital
Providence, Rhode Island, United States, 02905
United States, Texas
Parkland Memorial Hospital
Dallas, Texas, United States, 75235
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Principal Investigator: Kathleen Moore Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT00104910     History of Changes
Other Study ID Numbers: GOG-9918, NCI-2009-00621, CDR0000413880, GOG-9918, GOG-9918, GOG-9918, U10CA027469
Study First Received: March 3, 2005
Last Updated: December 12, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Squamous Cell
Uterine Cervical Neoplasms
Small Cell Lung Carcinoma
Carcinoma, Small Cell
Carcinoma, Adenosquamous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Complex and Mixed
Antibodies
Antibodies, Monoclonal
Cetuximab
Cisplatin

ClinicalTrials.gov processed this record on August 28, 2014