Mapatumumab, Cisplatin and Radiotherapy for Advanced Cervical Cancer

Inclusion Criteria:

1. Patients with histologically or cytologically confirmed stage IB2, IIA2, IIB, III, and IVA cervical cancer, according to the FIGO classification
2. Adequate bone marrow, renal and liver function:

   * Absolute neutrophil count ≥ 1.5 x 109 /L.
   * Platelet count ≥ 100 x 109 /L.
   * Serum creatinine level ≤ 1.5 x upper limit of normal (ULN).
   * Total bilirubin \< 1.25 x ULN.
   * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN.
3. Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Scale.
4. Age 18 years or older.
5. Life expectancy of ≥ 12 weeks.
6. Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study and follow-up procedures.

Exclusion Criteria:

1. Any co-morbid condition that in the judgment of the investigator renders the subject at high risk of treatment complications or reduces the possibility of assessing clinical effect.
2. Cytotoxic agent, hormonal therapy, or radiation therapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C) prior to day 1, cycle 1; investigational agent within 4 weeks prior to day 1, cycle 1.
3. Need for concomitant anticancer therapy (surgery, radiation therapy, chemotherapy, immunotherapy, radiofrequency ablation) or other investigational agents during the study treatment period.
4. Major surgery within 4 weeks before enrollment; minor surgery (except for insertion of vascular access device) within 2 weeks before enrollment; or not yet recovered from the effects of the surgery.
5. Systemic steroids within 1 week before enrollment except steroids used as part of an antiemetic regimen or maintenance-dose steroids for non-cancerous disease.
6. History of any infection requiring hospitalization or antibiotics within 2 weeks before enrollment.
7. Known brain or spinal cord metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids.
8. Known human immunodeficiency virus infection.
9. Unstable angina, myocardial infarction, cerebrovascular accident, \> Class II congestive heart failure according to the New York Heart Association Classification for Congestive Heart Failure within 6 months before enrollment.
10. Pregnant female or nursing mother.