Cetuximab, Cisplatin, and Radiotherapy in Women With Locally Advanced Cervical Carcinoma

An Exploratory Pharmacogenomic Study of Neoadjuvant Cetuximab Followed by Cisplatin, Radiotherapy, and Cetuximab in Women With Newly Diagnosed Locally Advanced or Metastatic Cervical Carcinoma

The anti-tumor activity of cetuximab prior to chemoradiotherapy and the safety and tolerability of cetuximab with concurrent chemoradiation will be determined in women with locally advanced or metastatic cervical carcinoma.

Study Overview

• Status: Unknown
• Conditions: Cancer of the Cervix
• Intervention / Treatment: Drug: Cetuximab

Detailed Description

• Women with Federation of Gynecology and Obstetrics (FIGO) Clinical Stage IB2-IVB carcinoma of the cervix
• Baseline cervical biopsy, blood samples, and FDG-PET/computed tomography (CT) scan
• Cetuximab 400 mg/m2 on day 1 followed by cetuximab 250 mg/m2 on days 8 and 15
• Repeat cervical biopsy and FDG-PET/CT scan following cetuximab monotherapy
• Radiation and weekly cisplatin 40 mg/m2 and cetuximab 250 mg/2 for 6 weeks
• Cetuximab 250 mg/m2 weekly for 12 weeks
• Repeat cervical biopsy (if tumor present) and FDG-PET/CT scan after completion of therapy
• Follow for tumor recurrence and survival

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Suspended
      • Washinton University School of Medicine
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Patients must have signed a Washington University, Human Studies Committee (HSC) approved, informed consent.
2. Patients must have primary, histologically documented FIGO Clinical Stage IB2-IVB invasive carcinoma of the uterine cervix with measurable disease amendable to repeated biopsy.
3. Patients must have an ECOG performance status of 0, 1, or 2 at study entry.
4. Patients, 18 years and older, must either be not of child bearing potential or have a negative pregnancy test within 7 days of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. Women should not breast feed while on this study.
5. Women must have a primary diagnosis of invasive carcinoma of the uterine cervix. Men are excluded from this study as a consequence of the diagnosis being investigated.
6. Patients must have had no previous treatment for invasive carcinoma of the uterine cervix.
7. Patients must be newly diagnosed with locally advanced or metastatic cervical carcinoma.
8. Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mcl; platelets > 100,000/mcl.
9. Renal function: creatinine ≤ 2.0 mg/dl.
10. Hepatic function: bilirubin ≤ 1.5 times upper limit normal (ULN); SGOT ≤ 2.5 times upper limit normal (ULN).
11. Patients with ureteral obstruction must be treated with stent or nephrostomy tube placement.
12. Patients with neuropathy (sensory and motor) must be ≤ grade 1 defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (June 10, 2003).

Exclusion Criteria:

1. Acute hepatitis or known HIV.
2. Active or uncontrolled infection.
3. Significant history of uncontrolled cardiac disease i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
4. Prior therapy which specifically and directly targets the EGFR pathway.
5. Prior severe infusion reaction to a monoclonal antibody.
6. Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).
7. A serious uncontrolled medical disorder that in the opinion of the Investigator would impair the ability of the subject to receive protocol therapy.
8. Unresolved ureteral obstruction.
9. Renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal transplant, that would require modification of radiation fields.
10. Known or documented brain metastases.
11. Any concurrent malignancy other than non-melanoma skin cancer. (Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial).
12. Prior radiation therapy to the abdomen and/or pelvis
13. Incarceration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To identify genes that may be identified as predictive of response to cetuximab	completion
To sequence the epidermal growth factor receptor (EGFR) to describe mutations in the receptor that may predict tumor response to cetuximab	completion
To evaluate the validity of fluorodeoxyglucose (FDG) uptake, as determined by positron emission tomography (PET) imaging, as a surrogate marker for response to cetuximab	completion

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the safety and tolerability of cetuximab with concurrent chemoradiation in women with locally advanced cervical carcinoma	weekly
To determine the progression-free and overall survival in women with locally advanced or metastatic cervical carcinoma treated with concurrent chemoradiation and cetuximab	every three months

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: Bristol-Myers Squibb; Eli Lilly and Company; Washington University School of Medicine
• Investigators: Principal Investigator: Linda R. Duska, M.D., University of Virginia

Publications and helpful links

General Publications

• Fracasso PM, Duska LR, Thaker PH, Gao F, Zoberi I, Dehdashti F, Siegel BA, Uliel L, Menias CO, Rehm PK, Goodner SA, Creekmore AN, Lothamer HL, Rader JS. An Exploratory Study of Neoadjuvant Cetuximab Followed by Cetuximab and Chemoradiotherapy in Women With Newly Diagnosed Locally Advanced Cervical Cancer. Am J Clin Oncol. 2022 Jul 1;45(7):286-293. doi: 10.1097/COC.0000000000000926. Epub 2022 Jun 7.

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Anticipated): February 1, 2012

Study Registration Dates

• First Submitted: February 14, 2006
• First Submitted That Met QC Criteria: February 14, 2006
• First Posted (Estimate): February 16, 2006

Study Record Updates

• Last Update Posted (Estimate): May 30, 2011
• Last Update Submitted That Met QC Criteria: May 26, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Cervical Cancer, Cetuximab, Phase II Clinical Trials; Stage IB2-IVB Carcinoma of the Cervix
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Carcinoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: IRB-HSR#13748; CA225243; HRPO #05-0702