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

Cancer of the Cervix Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00292955
• Other study ID #: IRB-HSR#13748
• Secondary ID: CA225243HRPO #05
• Status: Recruiting
• Phase: Phase 2
• First received: February 14, 2006
• Last updated: May 26, 2011
• Start date: February 2006

Study information

• Verified date: May 2011
• Source: University of Virginia
• Contact: Meredith Gross, M.S.
• Phone: 434-924-0436
• Email: mpg8b[@]virginia.edu
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer of the Cervix
• Uterine Cervical Neoplasms

Intervention

Drug:
• Cetuximab
monotherapy (day 1), then weekly thereafter along with radiation. dose is at 200mg/m2.

Locations

Country	Name	City	State
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Washinton University School of Medicine	St. Louis	Missouri

Sponsors (4)

Lead Sponsor	Collaborator
University of Virginia	Bristol-Myers Squibb, ImClone LLC, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To identify genes that may be identified as predictive of response to cetuximab		completion	No
Primary	To sequence the epidermal growth factor receptor (EGFR) to describe mutations in the receptor that may predict tumor response to cetuximab		completion	No
Primary	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	No
Secondary	To determine the safety and tolerability of cetuximab with concurrent chemoradiation in women with locally advanced cervical carcinoma		weekly	Yes
Secondary	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	No