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Combination Chemotherapy With CS-1008 to Treat Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00945191
Recruitment Status : Completed
First Posted : July 24, 2009
Results First Posted : November 18, 2020
Last Update Posted : April 8, 2021
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE July 22, 2009
First Posted Date  ICMJE July 24, 2009
Results First Submitted Date  ICMJE October 27, 2020
Results First Posted Date  ICMJE November 18, 2020
Last Update Posted Date April 8, 2021
Actual Study Start Date  ICMJE October 6, 2009
Actual Primary Completion Date August 23, 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 27, 2020)
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 [ Time Frame: Baseline up to first documented objective response, disease progression, or study withdrawal, up to 1 year 10 months ]
The best overall response is the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], unconfirmed CR, unconfirmed PR, stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the participant withdraws from the study. If there is no tumor assessment after the first dose of study drug, the best overall response is classified as Inevaluable. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions. Objective response rate was defined as confirmed CR and confirmed PR.
Original Primary Outcome Measures  ICMJE
 (submitted: July 23, 2009)
percentage of subjects with complete response after 6 cycles of treatment based on RECIST criteria [ Time Frame: 18 weeks = 6 cycles ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 27, 2020)
  • 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 [ Time Frame: 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 ]
    A sum of the diameters for all target lesions will be calculated and reported as the baseline sum of diameters, defined as the last non-missing value before initial administration of study treatment. The baseline sum of diameters will be used as reference for characterization of the objective tumor response. The change from baseline in the sum of longest diameters of target lesions is being reported. Negative values indicate an improvement in tumor reduction.
  • 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 [ Time Frame: Baseline up to 30 days after last dose, up to 1 year 10 months postdose ]
    Treatment-emergent adverse events (TEAEs) were defined as those events that occur, having been absent before the study, or worsen in severity after the initiation of CS-1008 and/or paclitaxel/docetaxel/carboplatin administration. All adverse events (AEs) were graded (1 to 5) according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0, where Grade 1 was mild, Grade 2 moderate, Grade 3 severe, Grade 4 life-threatening or disabling, and Grade 5 death related to AE.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2009)
  • objective response rate (all subjects) [ Time Frame: 18 weeks = 6 cycles ]
  • duration of complete response [ Time Frame: 18 weeks = 6 cycles ]
  • overall survival (subjects that achieve a complete response) [ Time Frame: 18 weeks = 6 cycles ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy With CS-1008 to Treat Ovarian Cancer
Official Title  ICMJE Phase 2 Study of CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ovarian Cancer Stage IIIC
  • Ovarian Cancer Stage IV
Intervention  ICMJE
  • Drug: CS-1008
    CS-1008 intravenous (IV) infusion 10 mg/kg on Day 1 of Cycle 1 and 8 mg/kg once every 3 weeks (1 cycle) for Cycle 2-6
  • Drug: Paclitaxel
    Paclitaxel 175 mg/m^2 IV infusion once every 3 weeks (1 cycle) for 6 cycles
    Other Name: Taxol
  • Drug: Carboplatin
    Carboplatin (target area under the concentration versus time curve of 6.0 mg/mL/min using the Calvert Formula) IV infusion once every 3 weeks (1 cycle) for 6 cycles
Study Arms  ICMJE Experimental: CS-1008 with paclitaxel and carboplatin
CS-1008 will be administered with paclitaxel and carboplatin.
  • Drug: CS-1008
  • Drug: Paclitaxel
  • Drug: Carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 24, 2012)
Original Estimated Enrollment  ICMJE
 (submitted: July 23, 2009)
Actual Study Completion Date  ICMJE August 23, 2011
Actual Primary Completion Date August 23, 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00945191
Other Study ID Numbers  ICMJE CS1008-A-U205
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP