Colorectal Cancer
Conditions
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.
Interventions
DRUGCS-7017
CS-7017
DRUGPlacebo
Placebo
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 18 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage Rate of Progression-free Survival Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy | At 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. |
| Percentage Rate of Overall Survival Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy | At 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 Chemotherapy | From 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. |
| Duration of Response for Responding Participants Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy | From 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. |
| 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 | Baseline 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. |
Countries
Czechia, France, Germany, Italy, Poland, Russia, Spain, Ukraine, United Kingdom
Participant flow
Recruitment details
A total of 84 participants who met all inclusion criteria and no exclusion criteria were enrolled at 46 clinic sites in Europe. Of the 84 participants enrolled, 83 received treatment.
Pre-assignment details
Participants who were randomized to treatment (CS-7017 0.5 mg or placebo) started treatment within 8 weeks of completing first-line therapy.
Participants by arm
| Arm | Count |
|---|---|
| CS-7017 0.5 mg Participants who were randomized to receive two 0.25 mg CS-7017 tablets (i.e. a dose of 0.5 mg) administered by mouth twice daily (PO BID), for a total of four tablets per day. | 41 |
| Placebo Participants who were randomized to receive matching placebo. | 43 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Progressive disease | 27 | 37 |
| Overall Study | Screen failure (not dosed) | 4 | 2 |
| Overall Study | Serious adverse event or adverse event | 9 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | CS-7017 0.5 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 7.69 | 60.9 years STANDARD_DEVIATION 9.73 | 62.4 years STANDARD_DEVIATION 8.88 |
| Age, Customized <65 years | 24 Participants | 26 Participants | 50 Participants |
| Age, Customized ≥65 years | 17 Participants | 17 Participants | 34 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 40 Participants | 41 Participants | 81 Participants |
| Sex: Female, Male Female | 19 Participants | 19 Participants | 38 Participants |
| Sex: Female, Male Male | 22 Participants | 24 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 41 | 23 / 42 |
| other Total, other adverse events | 41 / 41 | 31 / 42 |
| serious Total, serious adverse events | 6 / 41 | 5 / 42 |
Outcome results
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.
Time frame: 18 weeks postdose
Population: PFS was assessed in the Full Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CS-7017 0.5 mg | 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 | 39.86 percentage of participants |
| Placebo | 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 | 25.00 percentage of participants |
p-value: <0.00012-sided P value for z test
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.
Time frame: From baseline up to disease progression or the development of unacceptable toxicity (whichever occurs first), up to approximately 3 years 3 months
Population: Best overall response and objective response rate were assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CS-7017 0.5 mg | 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 | Objective response (confirmed CR+PR) | 6 Participants |
| CS-7017 0.5 mg | 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 | Progressive disease | 20 Participants |
| CS-7017 0.5 mg | 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 | Unconfirmed CR | 0 Participants |
| CS-7017 0.5 mg | 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 | Confirmed CR | 5 Participants |
| CS-7017 0.5 mg | 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 | Unconfirmed PR | 0 Participants |
| CS-7017 0.5 mg | 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 | Confirmed PR | 1 Participants |
| CS-7017 0.5 mg | 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 | Inevaluable | 3 Participants |
| CS-7017 0.5 mg | 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 | Best overall response of SD or better | 16 Participants |
| CS-7017 0.5 mg | 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 | Stable disease | 10 Participants |
| Placebo | 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 | Best overall response of SD or better | 12 Participants |
| Placebo | 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 | Stable disease | 8 Participants |
| Placebo | 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 | Progressive disease | 27 Participants |
| Placebo | 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 | Inevaluable | 3 Participants |
| Placebo | 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 | Confirmed PR | 0 Participants |
| Placebo | 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 | Objective response (confirmed CR+PR) | 1 Participants |
| Placebo | 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 | Unconfirmed CR | 0 Participants |
| Placebo | 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 | Unconfirmed PR | 3 Participants |
| Placebo | 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 | Confirmed CR | 1 Participants |
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.
Time frame: From the date of first objective response (confirmed and unconfirmed CR or PR) to date of progressive disease, up to 3 years 3 months
Population: Duration of response was assessed in the Full Analysis Set. Number Analyzed for each Row represents only the participants with CR or PR (confirmed and unconfirmed) and SD.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CS-7017 0.5 mg | 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 (confirmed and unconfirmed) | 33.57 weeks | Standard Deviation 25.88 |
| CS-7017 0.5 mg | 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 (confirmed responses) | 33.57 weeks | Standard Deviation 25.88 |
| CS-7017 0.5 mg | 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 stable disease | 26.16 weeks | Standard Deviation 10.68 |
| Placebo | 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 (confirmed and unconfirmed) | 15.96 weeks | Standard Deviation 14.86 |
| Placebo | 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 stable disease | 22.52 weeks | Standard Deviation 8.01 |
| Placebo | 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 (confirmed responses) | 37.86 weeks | — |
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.
Time frame: Baseline up to 30 days after last study dose, up to 3 years 3 months
Population: Adverse events were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CS-7017 0.5 mg | 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 | Any Related TEAE | 37 Participants |
| CS-7017 0.5 mg | 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 | Anaemia | 6 Participants |
| CS-7017 0.5 mg | 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 | Oedema | 3 Participants |
| CS-7017 0.5 mg | 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 | Any Gastrointestinal Disorder | 6 Participants |
| CS-7017 0.5 mg | 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 | Any Investigations | 22 Participants |
| CS-7017 0.5 mg | 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 | Fatigue | 6 Participants |
| CS-7017 0.5 mg | 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 | Localised oedema | 3 Participants |
| CS-7017 0.5 mg | 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 | Oedema peripheral | 16 Participants |
| CS-7017 0.5 mg | 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 | Weight increased | 20 Participants |
| CS-7017 0.5 mg | 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 | Any Metabolism and Nutrition Disorder | 6 Participants |
| CS-7017 0.5 mg | 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 | Fluid retention | 5 Participants |
| CS-7017 0.5 mg | 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 | Any Respiratory, Thoracic, & Mediastinal Disorder | 8 Participants |
| CS-7017 0.5 mg | 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 | Dyspnoea | 4 Participants |
| CS-7017 0.5 mg | 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 | Pleural effusion | 3 Participants |
| CS-7017 0.5 mg | 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 | Any Skin and Subcutaneous Tissue Disorder | 5 Participants |
| CS-7017 0.5 mg | 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 | Any Blood and Lymphatic System Disorder | 7 Participants |
| CS-7017 0.5 mg | 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 | Any General Disorder& Administration Site Disorder | 23 Participants |
| CS-7017 0.5 mg | 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 | Face oedema | 4 Participants |
| Placebo | 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 | Dyspnoea | 0 Participants |
| Placebo | 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 | Any Related TEAE | 16 Participants |
| Placebo | 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 | Weight increased | 5 Participants |
| Placebo | 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 | Anaemia | 0 Participants |
| Placebo | 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 | Any Blood and Lymphatic System Disorder | 0 Participants |
| Placebo | 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 | Oedema | 0 Participants |
| Placebo | 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 | Any Metabolism and Nutrition Disorder | 3 Participants |
| Placebo | 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 | Any Gastrointestinal Disorder | 2 Participants |
| Placebo | 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 | Pleural effusion | 0 Participants |
| Placebo | 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 | Any Investigations | 7 Participants |
| Placebo | 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 | Any Respiratory, Thoracic, & Mediastinal Disorder | 0 Participants |
| Placebo | 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 | Any Skin and Subcutaneous Tissue Disorder | 3 Participants |
| Placebo | 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 | Fluid retention | 2 Participants |
| Placebo | 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 | Fatigue | 3 Participants |
| Placebo | 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 | Face oedema | 1 Participants |
| Placebo | 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 | Localised oedema | 0 Participants |
| Placebo | 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 | Any General Disorder& Administration Site Disorder | 6 Participants |
| Placebo | 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 | Oedema peripheral | 2 Participants |
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.
Time frame: At 3, 6, 9, and 12 months postdose
Population: OS was assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CS-7017 0.5 mg | 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 rate at 3 months | 100.0 percentage of participants |
| CS-7017 0.5 mg | 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 rate at 6 months | 87.2 percentage of participants |
| CS-7017 0.5 mg | 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 rate at 9 months | 74.4 percentage of participants |
| CS-7017 0.5 mg | 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 rate at 12 months | 68.4 percentage of participants |
| Placebo | 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 rate at 12 months | 55.4 percentage of participants |
| Placebo | 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 rate at 3 months | 92.9 percentage of participants |
| Placebo | 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 rate at 9 months | 75.2 percentage of participants |
| Placebo | 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 rate at 6 months | 85.5 percentage of participants |
p-value: 0.1213Log Rank
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.
Time frame: At 12, 24, and 30 weeks postdose
Population: PFS was assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CS-7017 0.5 mg | 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 at 24 weeks | 29.9 percentage of participants |
| CS-7017 0.5 mg | 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 at 12 weeks | 62.0 percentage of participants |
| CS-7017 0.5 mg | 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 at 30 weeks | 29.9 percentage of participants |
| Placebo | 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 at 24 weeks | 15.0 percentage of participants |
| Placebo | 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 at 12 weeks | 47.5 percentage of participants |
| Placebo | 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 at 30 weeks | 12.5 percentage of participants |
p-value: 0.038Log Rank
p-value: 0.1773Peto-Peto-Prentice
p-value: 0.2844Wilcoxon (Mann-Whitney)
p-value: 0.114Tarone-Ware