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Study of CS-7017 in Colorectal Cancer Patients Who Have Achieved Disease Control Following First-Line Chemotherapy

Phase 2
Terminated
Conditions
Colorectal Cancer
Interventions
Drug: Placebo
Registration Number
NCT00986440
Lead Sponsor
Daiichi Sankyo
Brief Summary

Monotherapy treatment with CS-7017 to assess progression-free-survival (PFS) of subjects who achieved an objective response of Disease Control on first line therapy with Folinic acid (leucovorin), Fluorouracil (5-FU), Oxaliplatin (Eloxatin) known as FOLFOX; or Folinic acid (leucovorin), Fluorouracil (5-FU), irinotecan (Camptosar) known as FOLFIRI.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
84
Inclusion Criteria
  • Patients with histologically confirmed, metastatic CRC that have achieved confirmed maximal benefit of DC following treatment with standard first line chemotherapy of a 5-fluoropyrimidine plus either oxaliplatin or irinotecan. Patients should be entered onto this trial within 8 weeks of completing first line therapy;

  • If CR was not achieved: measurable disease, i.e. at minimum one unidimensionally-measurable target lesion according to RECIST (Response Evaluation Criteria in Solid Tumors);

  • Age >= 18 years and Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 at study entry;

  • Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, Version 3.0, grade =< 1;

  • Adequate organ and bone marrow function as evidenced by:

    • Haemoglobin >= 10 g/dL (transfusion and/or growth factor support allowed);
    • Absolute neutrophil count (ANC) >= 1.5 x 109/L;
    • Platelet count >= 100 x 109/L;
    • Serum creatinine =< 1.5 x ULN or creatinine clearance >60 mL/min;
    • AST and alkaline phosphatase <2.5 x ULN if without liver metastasis and =< 5.0 x ULN if liver metastasis;
    • Total bilirubin =< 2.0 x ULN;
    • Prothrombin time (PT)/International Normalised Ratio (INR) within normal limits (WNL) unless therapeutically anticoagulated;
  • Women of childbearing potential and men must be willing to consent to using highly effective methods of contraception (eg, hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device) while on treatment and for at least 3 months thereafter;

  • Males with the potential to father children must use two of the following methods of contraception acceptable for the study (e.g. hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device) while on trial treatment and for at least 3 months thereafter.

  • All female subjects of childbearing potential must have a negative pregnancy test (plasma or urine) result within 7 days before initiating study treatment;

  • Baseline laboratory tests and tumor assessments must have been performed within 2 weeks before initiating study treatment;

  • Subjects 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 IEC-approved ICF before performance of any study specific procedures or tests.

Exclusion Criteria
  • Anticipation of need for a major surgical procedure or RT during the study;
  • Treatment with chemotherapy, hormonal therapy, minor surgery, or any investigational agent within 4 weeks before study enrolment. Treatment with immunotherapy, biological therapy, or major surgery within 6 weeks before study enrolment. Treatment with RT within 1 week before study enrolment.
  • History of any of the following conditions: diabetes mellitus requiring treatment with insulin or oral agents;
  • Concomitant use of other TZDs;
  • Myocardial infarction with significant impairment of cardiac function (e.g., ejection fraction =< 50%); severe/unstable angina pectoris; coronary/peripheral artery bypass graft; congestive heart failure; cerebrovascular accident (CVA) or transient ischemic attack (TIA), pulmonary embolism, or other clinically significant thromboembolic event; clinically significant pulmonary disease (e.g., severe chronic obstructive pulmonary disease [COPD] or asthma);
  • Brain metastasis; an uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis;
  • Pleural or pericardial effusion. Subjects with minimal pleural effusion may be eligible upon request by Investigator and approval by Sponsor;
  • Clinically significant active infection that requires antibiotic therapy or Human Immunodeficiency Virus (HIV) positive subjects receiving antiretroviral therapy;
  • Pregnant or breast feeding;
  • Known history of severe hypersensitivity reactions to any of the components of CS 7017 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;

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo matching CS-7017
CS-7017CS-7017-
Primary Outcome Measures
NameTimeMethod
Percentage Rate of Progression-free Survival at 18 Weeks Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy18 weeks postdose

Progression-free survival (PFS) was defined as the time from enrollment to the date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions.

Secondary Outcome Measures
NameTimeMethod
Percentage Rate of Progression-free Survival Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line ChemotherapyAt 12, 24, and 30 weeks postdose

Progression-free survival (PFS) was defined as the time from enrollment to the date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions.

Duration of Response for Responding Participants Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line ChemotherapyFrom the date of first objective response (confirmed and unconfirmed CR or PR) to date of progressive disease, up to 3 years 3 months

Duration of response was defined for participants with confirmed CR or PR and confirmed and unconfirmed CR or PR as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progressive disease. Duration of SD was defined for participants whose best response was SD as the time from the randomization date to the date of the first documentation of progressive disease. Duration of response was estimated using Kaplan Meier methods.

Percentage Rate of Overall Survival Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line ChemotherapyAt 3, 6, 9, and 12 months postdose

Overall survival (OS) was defined as the time from the date of enrollment to the date of death and assessed by Kaplan Meier analysis.

Best Overall Response and Objective Response Rate Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line ChemotherapyFrom baseline up to disease progression or the development of unacceptable toxicity (whichever occurs first), up to approximately 3 years 3 months

The best overall response was defined as 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 withdrew from the study. If there was no tumor assessment after the first dose of study drug, the best overall response was classified as Inevaluable. Based on RECIST v1.0, 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 progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.

Number of Participants With Treatment-Emergent Adverse Events Related to Study Drug With an Incidence of ≥5% Following Use of CS-7017 Or Placebo in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line ChemotherapyBaseline up to 30 days after last study dose, up to 3 years 3 months

A treatment-emergent adverse event (TEAE) was defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event that occurs more than 30 days after the last dose of study medication is not included as a TEAE unless it is considered related to treatment. If relationship is missing, the AE is also considered to be related to the drug.

Trial Locations

Locations (39)

Institute for Cancer Research and Treatment - IRCC

🇮🇹

Candiolo, Torino, Italy

Wojewodzki Szpital Specjalistyczny

🇵🇱

Bytom, Poland

NZOZ ONKOLOG s.c.

🇵🇱

Warszawa, Poland

Central Clinical Hospital #1

🇷🇺

Moscow, Russian Federation

Unita Operativa di Oncologia Medica

🇮🇹

Lecce, Italy

Policlinico Santa Maria alle Scotte

🇮🇹

Siena, Italy

Klinikum rechts der Isar

🇩🇪

München, Germany

H.Clinic I Provincial de Barcelona

🇪🇸

Barcelona, Villaroel, Spain

Ospedale San Martino

🇮🇹

Genova, Italy

Aberdeen Royal Infirmary

🇬🇧

Aberdeen, United Kingdom

Onkologische Praxis Donauwörth

🇩🇪

Donauwörth, Germany

Universitätsklinikum Halle Klinik und Poliklinik für Innere Medizin

🇩🇪

Halle, Germany

Medical Radiological Research Centre

🇷🇺

Obninsk, Kaluga, Russian Federation

Azienda Ospedaliero Universitaria Santa Maria della Misericordia

🇮🇹

Udine, Italy

Fakulti nemocnice Brno

🇨🇿

Brno, Czechia

Fakultni nemocnice Olomouc

🇨🇿

Olomouc, Czechia

Hopitaux civils de colmar

🇫🇷

Colmar, Cedex, France

Nemocnice Znojmo, p.o., Oddeleni radiacni a klinicke onkologie

🇨🇿

Znojmo, Czechia

Service d'Oncologie Medicale

🇫🇷

Rennes, Cedex, France

Centre Hospitalier Prive Saint Gregoire

🇫🇷

Saint Grégoire, France

St-Petersburg State Institution of Public Health

🇷🇺

St Petersburg, Russian Federation

Hospital Mútua de Terrassa

🇪🇸

Terrassa (Barcelona), Spain

Clinica Universitaria de Navarra

🇪🇸

Pamplona, Spain

Christie Hospital

🇬🇧

Manchester, United Kingdom

St.Bartholomew's Hospital

🇬🇧

London, United Kingdom

Hopital Edouard Herriot

🇫🇷

Lyon, Cedex, France

Sumy Regional Oncology Center

🇺🇦

Sumy, Ukraine

Federal State Institution of Healthcare Clinical Hospital # 122 n.a.L.G Sokolov

🇷🇺

St-Petersburg, Russian Federation

Volyn regional oncology dispensary

🇺🇦

Lutsk, Volyn, Ukraine

Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie

🇵🇱

Gliwice, Poland

Russian Oncology Research Centre n.a. Blokhin, RAMS

🇷🇺

Moscow, Russian Federation

VESALIUS Sp. z o.o.

🇵🇱

Krakow, Poland

Tula Regional Oncology dispensary

🇷🇺

Tula, Russian Federation

Kyiv City Oncology Hospital

🇺🇦

Kiev, Ukraine

Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku

🇵🇱

Bialystok, Poland

Kazan State Medical University

🇷🇺

Kazan, Tatarstan, Russian Federation

NUZ Semashko Central Clinical Hospital

🇷🇺

Moscow, Russian Federation

Mount Vernon Cancer Centre

🇬🇧

Northwood, Middlesex, United Kingdom

UCLH Cancer Clinical Trials Unit

🇬🇧

London, United Kingdom

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