A Phase 1b/2 Study With the Agonistic TRAIL-R1 Antibody, Mapatumumab, in Combination With Cisplatin and Radiotherapy as a First Line Therapy in Patients With Advanced Cervical Cancer.
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.
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
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
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.