Clinical trial NCT00945191: Combination Chemotherapy With CS-1008 to Treat Ovarian Cancer
Official title: Phase 2 Study of CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer Stage IIIC
Ovarian Cancer Stage IV
Keywords: Ovarian Cancer Stage IIIC
Ovarian Cancer Stage IV
CS-1008
Paclitaxel
Carboplatin
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2009-07-24
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial assessed the effect of treatment with CS-1008 in combination with paclitaxel/carboplatin on response in patients with locally advanced or metastatic ovarian cancer.

Detailed description: This trial assessed CS-1008 administered in combination with paclitaxel/carboplatin to patients with Stage IIIC or IV ovarian cancer who had suboptimal debulking surgery with residual measurable/evaluable disease and who had not received prior therapy for their disease. The effect of this first-line treatment in patients was assessed by complete response rate.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed, epithelial carcinoma of the ovary or primary peritoneal carcinoma (International Federation of Gynecology and Obstetrics \[FIGO\] Stage IIIC or IV).

(Participants with the following histologic epithelial cell types are eligible for the study: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified.)

* Enrollment within 6 weeks after surgical resection (debulking).
* Residual tumor masses \> 1 cm and objectively measurable/evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
* No prior therapy for ovarian cancer (ie, chemotherapy or radiotherapy \[RT\] to the abdomen or pelvis) other than surgical debulking of disease.
* At least 18 years of age.
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
* Adequate organ and bone marrow function as evidenced by:

  * Absolute neutrophil count ≥ 1,500/µL (equivalent to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 grade 1)
  * Platelet count ≥ 100,000/µL (CTCAE grade 0 to 1)
  * Hemoglobin ≥ 9 g/dL
  * Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) (CTCAE grade 1)
  * Bilirubin ≤ 1.5 x ULN (CTCAE grade 1)
  * Aspartate aminotransferase (AST) and alkaline phosphatase ≤ 2.5 x ULN (CTCAE grade 1)
* Adequate neurologic function (ie, sensory and motor neuropathy ≤ CTCAE grade 1).
* Women of childbearing potential must be willing to consent to using effective contraception while on treatment and for 3 months thereafter.
* All subjects of childbearing potential must have a negative pregnancy test (serum or urine) result ≤ 72 hours before initiating study treatment.
* Participants must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an institutional review board-approved informed consent form (ICF) before performance of any study-specific procedures or tests.

Exclusion Criteria:

* Prior invasive malignant disease within 5 years except for squamous cell or basal cell carcinoma.
* Current diagnosis of borderline epithelial ovarian tumor (formerly "tumors of low malignant potential") or recurrent ovarian epithelial cancer.
* Positive human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg) because of the potential for additional toxicity from the treatment regimen.
* Anticipation of need for a major surgical procedure or radiotherapy (RT) during the study.
* History of any of the following conditions within 6 months before study enrollment: myocardial infarction; severe/unstable angina pectoris; coronary/peripheral artery bypass graft; New York Heart Association (NYHA) class III or IV congestive heart failure; cerebrovascular accident or transient ischemic attack, pulmonary embolism, or other clinically significant thromboembolic event; clinically significant pulmonary disease (eg, severe chronic obstructive pulmonary disease or asthma).
* Clinically active brain metastasis (ie, untreated, still requiring therapy with steroids or RT, or with progression within 4 weeks after completion of RT); an uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis.
* Pregnant or lactating.
* Prior treatment with CS-1008, other agonistic DR5 antibodies, or tumor necrosis factor-related apoptosis inducing ligand (TRAIL).
* Known history of hypersensitivity reactions to any of the components of CS-1008, paclitaxel (or docetaxel), or carboplatin formulations.
* Serious intercurrent medical or psychiatric illnesses or any other conditions that in the opinion of the Investigator would impair the ability to give informed consent or unacceptably reduce protocol compliance or safety of the study treatment.

Primary outcomes:
measure: Best Overall Response and Objective Response Rate Following Treatment With CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer
timeFrame: Baseline up to first documented objective response, disease progression, or study withdrawal, up to 1 year 10 months
Secondary outcomes:
measure: Change From Baseline in the Sum of Longest Diameters of Target Lesions Following Treatment With CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer
timeFrame: Baseline to Cycle 3, Week 3 Day 1; Cycle 6, Week 3 Day 1 (each cycle 21 days) up to end of study, approximately 1 year 10 months postdose
measure: Participants With Treatment-Emergent Adverse Events Grade 3 or Higher by System Organ Class and Preferred Term Following Treatment With CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer
timeFrame: Baseline up to 30 days after last dose, up to 1 year 10 months postdose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ. Alabama
state: Alabama
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: