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
Overview
- Phase
- Phase 1
- Intervention
- Internal Radiation Therapy
- Conditions
- Cervical Adenocarcinoma
- Sponsor
- Gynecologic Oncology Group
- Enrollment
- 64
- Locations
- 15
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
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.
Investigators
Eligibility 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
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Internal Radiation Therapy
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.
Intervention: 3-Dimensional Conformal Radiation Therapy
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.
Intervention: Cetuximab
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.
Intervention: Cisplatin
Outcomes
Primary Outcomes
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
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
Secondary Outcomes
- Progression-free survival(From study entry until disease progression, death or date of last contact, up to 1 year)
- Site of recurrence, loco-regional vs distant, assessed by clinical and radiological evaluation(From study entry until disease progression, death or date of last contact, up to 1 year)
- Frequency of chronic toxicities, assessed by CTCAE v3.0(From study entry until disease progression, death or date of last contact, up to 1 year)