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

A Randomized, Double-Blind Placebo-Controlled Phase 2 Study of CS-7017 in Colorectal Cancer Patients Who Have Achieved Disease Control Following First-Line Chemotherapy

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Placebo; Drug: CS-7017

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 62500
    • Fakulti nemocnice Brno
  • Olomouc, Czechia, 77520
    • Fakultni Nemocnice Olomouc
  • Znojmo, Czechia, 66902
    • Nemocnice Znojmo, p.o., Oddeleni radiacni a klinicke onkologie
• France
  • Saint Grégoire, France, 35768
    • Centre Hospitalier Privé Saint Grégoire
  • Cedex
    • Colmar, Cedex, France, 68024
      • Hôpitaux civils de Colmar
    • Lyon, Cedex, France, 69437
      • Hôpital Edouard Herriot
    • Rennes, Cedex, France, 35042
      • Service d'Oncologie Médicale
• Germany
  • Donauwörth, Germany, 86609
    • Onkologische Praxis Donauwörth
  • Halle, Germany, 06120
    • Universitätsklinikum Halle Klinik und Poliklinik für Innere Medizin
  • München, Germany, 81675
    • Klinikum rechts der Isar
• Italy
  • Genova, Italy
    • Ospedale San Martino
  • Lecce, Italy
    • Unita Operativa di Oncologia Medica
  • Siena, Italy, 53100
    • Policlinico Santa Maria alle Scotte
  • Udine, Italy, 33100
    • Azienda Ospedaliero Universitaria Santa Maria della Misericordia
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Institute for Cancer Research and Treatment - IRCC
• Poland
  • Bialystok, Poland, 15-027
    • Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku
  • Bytom, Poland, 41-902
    • Wojewodzki Szpital Specjalistyczny
  • Gliwice, Poland, 44-101
    • Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie
  • Krakow, Poland, 31-108
    • VESALIUS Sp. z o.o.
  • Warszawa, Poland, 01-002
    • NZOZ ONKOLOG s.c.
• Russian Federation
  • Moscow, Russian Federation, 125367
    • Central Clinical Hospital #1
  • Moscow, Russian Federation, 115478
    • Russian Oncology Research Centre n.a. Blokhin, RAMS
  • Moscow, Russian Federation, 129128
    • NUZ Semashko Central Clinical Hospital
  • St Petersburg, Russian Federation, 198255
    • St-Petersburg State Institution of Public Health
  • St-Petersburg, Russian Federation, 194291
    • Federal State Institution of Healthcare Clinical Hospital # 122 n.a.L.G Sokolov
  • Tula, Russian Federation, 300053
    • Tula Regional Oncology Dispensary
  • Kaluga
    • Obninsk, Kaluga, Russian Federation, 249030
      • Medical Radiological Research Centre
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 4200111
      • Kazan State Medical University
• Spain
  • Pamplona, Spain, 31008
    • Clinica Universitaria de Navarra
  • Terrassa (Barcelona), Spain, 08221
    • Hospital Mútua de Terrassa
  • Villaroel
    • Barcelona, Villaroel, Spain, 170
      • H.Clinic I Provincial de Barcelona
• Ukraine
  • Kiev, Ukraine, 03115
    • Kyiv City Oncology Hospital
  • Sumy, Ukraine, 40005
    • Sumy Regional Oncology Center
  • Volyn
    • Lutsk, Volyn, Ukraine
      • Volyn Regional Oncology Dispensary
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Aberdeen Royal Infirmary
  • London, United Kingdom, EC1A 7BE
    • St.Bartholomew's Hospital
  • London, United Kingdom, NW1 2PQ
    • UCLH Cancer Clinical Trials Unit
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CS-7017	Drug: CS-7017; CS-7017
Placebo Comparator: Placebo; Placebo matching CS-7017	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Chemotherapy	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.	18 weeks postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Rate of Progression-free Survival Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy	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.	At 12, 24, and 30 weeks postdose
Percentage Rate of Overall Survival Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy	Overall survival (OS) was defined as the time from the date of enrollment to the date of death and assessed by Kaplan Meier analysis.	At 3, 6, 9, and 12 months postdose
Best Overall Response and Objective Response Rate Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy	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.	From baseline up to disease progression or the development of unacceptable toxicity (whichever occurs first), up to approximately 3 years 3 months
Duration of Response for Responding Participants Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy	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.	From the date of first objective response (confirmed and unconfirmed CR or PR) to date of progressive disease, up to 3 years 3 months
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 Chemotherapy	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.	Baseline up to 30 days after last study dose, up to 3 years 3 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2009
• Primary Completion (Actual): October 29, 2012
• Study Completion (Actual): October 29, 2012

Study Registration Dates

• First Submitted: September 29, 2009
• First Submitted That Met QC Criteria: September 29, 2009
• First Posted (Estimate): September 30, 2009

Study Record Updates

• Last Update Posted (Actual): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Efatutazone
• Other Study ID Numbers: CS7017-A-E201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR