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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00986440
• Other study ID #: CS7017-A-E201
• Status: Terminated
• Phase: Phase 2
• Start date: July 31, 2009
• Est. completion date: October 29, 2012

Study information

• Verified date: November 2020
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 84
• Est. completion date: October 29, 2012
• Est. primary completion date: October 29, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• CS-7017
CS-7017
• Placebo
Placebo

Locations

Country	Name	City	State
Czechia	Fakulti nemocnice Brno	Brno
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Nemocnice Znojmo, p.o., Oddeleni radiacni a klinicke onkologie	Znojmo
France	Hopitaux civils de colmar	Colmar	Cedex
France	Hopital Edouard Herriot	Lyon	Cedex
France	Service d'Oncologie Medicale	Rennes	Cedex
France	Centre Hospitalier Prive Saint Gregoire	Saint Grégoire
Germany	Onkologische Praxis Donauwörth	Donauwörth
Germany	Universitätsklinikum Halle Klinik und Poliklinik für Innere Medizin	Halle
Germany	Klinikum rechts der Isar	München
Italy	Institute for Cancer Research and Treatment - IRCC	Candiolo	Torino
Italy	Ospedale San Martino	Genova
Italy	Unita Operativa di Oncologia Medica	Lecce
Italy	Policlinico Santa Maria alle Scotte	Siena
Italy	Azienda Ospedaliero Universitaria Santa Maria della Misericordia	Udine
Poland	Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku	Bialystok
Poland	Wojewodzki Szpital Specjalistyczny	Bytom
Poland	Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie	Gliwice
Poland	VESALIUS Sp. z o.o.	Krakow
Poland	NZOZ ONKOLOG s.c.	Warszawa
Russian Federation	Kazan State Medical University	Kazan	Tatarstan
Russian Federation	Central Clinical Hospital #1	Moscow
Russian Federation	NUZ Semashko Central Clinical Hospital	Moscow
Russian Federation	Russian Oncology Research Centre n.a. Blokhin, RAMS	Moscow
Russian Federation	Medical Radiological Research Centre	Obninsk	Kaluga
Russian Federation	St-Petersburg State Institution of Public Health	St Petersburg
Russian Federation	Federal State Institution of Healthcare Clinical Hospital # 122 n.a.L.G Sokolov	St-Petersburg
Russian Federation	Tula Regional Oncology dispensary	Tula
Spain	H.Clinic I Provincial de Barcelona	Barcelona	Villaroel
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Hospital Mútua de Terrassa	Terrassa (Barcelona)
Ukraine	Kyiv City Oncology Hospital	Kiev
Ukraine	Volyn regional oncology dispensary	Lutsk	Volyn
Ukraine	Sumy Regional Oncology Center	Sumy
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	St.Bartholomew's Hospital	London
United Kingdom	UCLH Cancer Clinical Trials Unit	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Mount Vernon Cancer Centre	Northwood	Middlesex

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

Czechia,  France,  Germany,  Italy,  Poland,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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