CS-7017 in Combination With Carboplatin/Paclitaxel in Subjects With Stage IIIb/IV Non-small Cell Lung Cancer (NSCLC)
Sponsor
Daiichi Sankyo Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT01199055
Collaborator
ICON Clinical Research (Industry)
16
1
1
16
1
Study Details
Study Description
Brief Summary
The primary objectives of this study are to evaluate the safety and tolerability of CS-7017 administered orally twice a day in combination with carboplatin and paclitaxel, and to assess the pharmacokinetics of CS-7017 in combination with carboplatin and paclitaxel.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
16 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1b Study of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC)
Study Start Date
:
Mar 1, 2010
Actual Primary Completion Date
:
Apr 1, 2011
Actual Study Completion Date
:
Jul 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CS-7017+Carboplatin/Paclitaxel Drug: CS-7017 from 0.25 mg twice a day (BID) to 0.50 mg BID for up to 4~6 cycles (1 cycle: 3 weeks) Drug: Carboplatin IV, Area under the curve (AUC) of 6 mg/mL*min, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks) Drug: Paclitaxel IV, 200mg/m^2, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks) |
Drug: CS-7017
Drug: CS-7017 from 0.25 mg BID to 0.50 mg BID for up to 4~6 cycles (1 cycle: 3 weeks)
Other Names:
Drug: Carboplatin
Drug: Carboplatin IV, AUC of 6 mg/mL*min, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks)
Other Names:
Drug: Paclitaxel
Drug: Paclitaxel IV, 200mg/m^2, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Geometric Means of Serum Free Form of CS-7017 (R-150033) After Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer [Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose]
The area under the concentration versus time curve during dosing interval (AUCtau) and up to the last quantifiable time (AUClast) of geometric means of CS-7017 are reported at selected cycles (C) and days (D).
- Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer [Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose]
The maximum serum concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D).
- Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer [Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose]
The time of maximum plasma concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D).
- Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group During Cycle 1 Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer [Baseline to end of Cycle 1, with each treatment cycle being 3 weeks]
Treatment-emergent adverse events (TEAEs) are defined as those adverse events that occur, having been absent before the study, or worsen in severity after the initiation of study drug.
Secondary Outcome Measures
- Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) [Baseline up to Week 18 postdose]
The best overall response is the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], stable disease [SD], and progressive disease [PD]) among all overall responses from the start of treatment until the participant withdraws from the study. Participants who did not have a tumor assessment, the best overall response is Not Evaluable (NE). The response rate was defined as the proportion of participants with a best overall response of CR or PR, ie, [confirmed and unconfirmed, (CR + PR) / number of participants]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, CR was defined as the disappearance of all target lesions, PR was defined as ≥30% decrease in the sum of diameters of target lesions, PD was defined as ≥20 increase in the smallest sum of diameters, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
- CS-7017-Related Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group After Administration of CS-7017 and Carboplatin/Paclitaxel in Chemotherapy-naïve Participants With Stage IIIb/IV Non-small Cell Lung Cancer [Baseline to 30 days after last dose, up to approximately 1 year]
Treatment-emergent adverse events (TEAEs) are defined as those adverse events that occur, having been absent before the study, or worsen in severity after the initiation of study drug. CS-7017-related TEAEs are those TEAEs that are related to CS-7017 in the relationship.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically or cytologically confirmed unresectable locally advanced or metastatic (stage IIIb or IV) non-small cell lung cancer (NSCLC)
-
No prior systemic therapy for NSCLC
-
Male or female ≥ 18 years of age
-
Anticipation of more than 3 months survival
-
Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1
-
Adequate organ and bone marrow function
Exclusion Criteria:
-
Anticipation of need for a major surgical procedure or radiation therapy during the study
-
Remaining influence of previous therapies such as radiotherapy, surgery, immunotherapy within 4 weeks prior to start of study treatment
-
History of any of the following events within 6 months prior to start of study treatment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class ≥I congestive heart failure (CHF), cerebrovascular accident or cerebral infarction, pulmonary embolism, deep vein thrombosis, or other clinically significant thromboembolic event; clinically significant pulmonary disease (eg, severe chronic-obstructive pulmonary disease (COPD) or asthma)
-
Severe edema, ascites fluid, pericardial or pleural effusion or pericardial involvement with the tumor within 6 months prior to start of study treatment, or which require steroid therapy/ diuretic therapy
-
Subjects with brain metastasis (defined as untreated, symptomatic or requiring steroids or anticonvulsant medications to control associated symptoms)
-
Subjects with clinically significant active infection which requires antibiotic therapy, or who are hepatitis B surface antigen (HBs)- or hepatitis C virus (HCV)- or human immunodeficiency virus (HIV)- positive and receiving antiretroviral therapy
-
Subjects with malabsorption syndrome, chronic diarrhea (lasting over 4 weeks), inflammatory bowel disease, or partial bowel obstruction
-
Diabetes mellitus requiring insulin, or a history of poor serum glucose control with the use of non-insulin diabetes medications
-
Treatment with thiazolidinediones (TZDs) within 4 weeks prior to start of study treatment
-
History of a second malignancy, with the exception of in situ cervical cancer or adequately treated basal cell or squamous cell carcinoma of the skin
-
Poorly-controlled blood pressure as judged by the Investigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Samsung Medical Center | Seoul | Gangnam-gu | Korea, Republic of | 135-710 |
Sponsors and Collaborators
- Daiichi Sankyo Co., Ltd.
- ICON Clinical Research
Investigators
- Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01199055
Other Study ID Numbers:
- CS7017-A-A108
First Posted:
Sep 10, 2010
Last Update Posted:
Jul 7, 2020
Last Verified:
Jun 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Daiichi Sankyo Co., Ltd.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 18 participants were screened for eligibility. Of the 18 participants who were screened, 16 participants who met all inclusion criteria and no exclusion criteria were enrolled from 17 March 2010 to 15 April 2011 at 1 site in South Korea. All 16 participants received treatment. |
|---|---|
| Pre-assignment Detail | This dose-escalating study included an initial and additional portion. Participants received CS-7017 combination treatment with carboplatin & paclitaxel (starting dose 0.25 mg twice daily [BID] in the initial portion). In the additional portion, the CS-7017 dose was determined (0.50 mg BID) based on the initial portion. |
| Arm/Group Title | CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion |
|---|---|---|---|
| Arm/Group Description | Participants who received 0.25 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.50 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.5 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. Cycle 1, Day 1: Carboplatin and paclitaxel only Cycle 1, Day 3: CS-7017 at the dose selected in initial portion Subsequent cycles: CS-7017 with carboplatin and paclitaxel |
| Period Title: Overall Study | |||
| STARTED | 3 | 4 | 9 |
| COMPLETED | 1 | 1 | 5 |
| NOT COMPLETED | 2 | 3 | 4 |
Baseline Characteristics
| Arm/Group Title | CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants who received 0.25 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.50 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.5 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. Cycle 1, Day 1: Carboplatin and paclitaxel only Cycle 1, Day 3: CS-7017 at the dose selected in initial portion Subsequent cycles: CS-7017 with carboplatin and paclitaxel | Total of all reporting groups |
| Overall Participants | 3 | 4 | 9 | 16 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
66.7%
|
2
50%
|
6
66.7%
|
10
62.5%
|
| >=65 years |
1
33.3%
|
2
50%
|
3
33.3%
|
6
37.5%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
59.7
(9.29)
|
62.3
(5.91)
|
58.9
(9.98)
|
59.9
(8.59)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
1
33.3%
|
0
0%
|
4
44.4%
|
5
31.3%
|
| Male |
2
66.7%
|
4
100%
|
5
55.6%
|
11
68.8%
|
| Region of Enrollment (participants) [Number] | ||||
| South Korea |
3
100%
|
4
100%
|
9
100%
|
16
100%
|
Outcome Measures
| Title | Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Geometric Means of Serum Free Form of CS-7017 (R-150033) After Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer |
|---|---|
| Description | The area under the concentration versus time curve during dosing interval (AUCtau) and up to the last quantifiable time (AUClast) of geometric means of CS-7017 are reported at selected cycles (C) and days (D). |
| Time Frame | Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion |
|---|---|---|---|
| Arm/Group Description | Participants who received 0.25 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.50 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.5 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. Cycle 1, Day 1: Carboplatin and paclitaxel only Cycle 1, Day 3: CS-7017 at the dose selected in initial portion Subsequent cycles: CS-7017 with carboplatin and paclitaxel |
| Measure Participants | 3 | 4 | 9 |
| Cycle 1, Week 1: AUCtau |
70.66
(54.11)
|
209.33
(131.40)
|
203.99
(91.34)
|
| Cycle 1, Week 1: AUClast |
49.57
(36.86)
|
87.23
(85.69)
|
81.54
(66.01)
|
| Cycle 2, Week 4: AUCtau |
132.47
(25.49)
|
345.56
(156.29)
|
400.89
(212.22)
|
| Cycle 2, Week 4: AUClast |
95.94
(15.84)
|
240.61
(107.09)
|
268.00
(134.40)
|
| Title | Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer |
|---|---|
| Description | The maximum serum concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D). |
| Time Frame | Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion |
|---|---|---|---|
| Arm/Group Description | Participants who received 0.25 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.50 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.5 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. Cycle 1, Day 1: Carboplatin and paclitaxel only Cycle 1, Day 3: CS-7017 at the dose selected in initial portion Subsequent cycles: CS-7017 with carboplatin and paclitaxel |
| Measure Participants | 3 | 4 | 9 |
| Cycle 1, Week 1: Cmax |
8.90
(7.01)
|
15.98
(16.77)
|
14.54
(9.75)
|
| Cycle 2, Week 4: Cmax,ss |
13.63
(1.77)
|
33.83
(15.42)
|
39.58
(18.63)
|
| Title | Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer |
|---|---|
| Description | The time of maximum plasma concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D). |
| Time Frame | Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion |
|---|---|---|---|
| Arm/Group Description | Participants who received 0.25 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.50 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.5 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. Cycle 1, Day 1: Carboplatin and paclitaxel only Cycle 1, Day 3: CS-7017 at the dose selected in initial portion Subsequent cycles: CS-7017 with carboplatin and paclitaxel |
| Measure Participants | 3 | 3 | 9 |
| Cycle 1, Week 1: Tmax |
3.90
|
3.00
|
5.95
|
| Cycle 2, Week 4: Tmax,ss |
3.17
|
3.98
|
3.88
|
| Title | Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group During Cycle 1 Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer |
|---|---|
| Description | Treatment-emergent adverse events (TEAEs) are defined as those adverse events that occur, having been absent before the study, or worsen in severity after the initiation of study drug. |
| Time Frame | Baseline to end of Cycle 1, with each treatment cycle being 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| TEAEs were assessed in the Safety Analysis Set. |
| Arm/Group Title | CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion |
|---|---|---|---|
| Arm/Group Description | Participants who received 0.25 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.50 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.5 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. Cycle 1, Day 1: Carboplatin and paclitaxel only Cycle 1, Day 3: CS-7017 at the dose selected in initial portion Subsequent cycles: CS-7017 with carboplatin and paclitaxel |
| Measure Participants | 3 | 4 | 9 |
| At least one TEAE |
3
100%
|
4
100%
|
9
100%
|
| Blood and lymphatic system disorders |
3
100%
|
2
50%
|
8
88.9%
|
| Neutropenia |
3
100%
|
2
50%
|
7
77.8%
|
| Anaemia |
0
0%
|
0
0%
|
5
55.6%
|
| Metabolism and Nutrition Disorders |
0
0%
|
2
50%
|
6
66.7%
|
| Decreased appetite |
0
0%
|
1
25%
|
6
66.7%
|
| Nervous System Disorders |
1
33.3%
|
1
25%
|
4
44.4%
|
| Neuropathy peripheral |
0
0%
|
1
25%
|
4
44.4%
|
| Respiratory, Thoracic and Mediastinal Disorders |
1
33.3%
|
0
0%
|
4
44.4%
|
| Pleural effusion |
0
0%
|
0
0%
|
4
44.4%
|
| Gastrointestinal Disorders |
2
66.7%
|
1
25%
|
6
66.7%
|
| Nausea |
2
66.7%
|
1
25%
|
1
11.1%
|
| Skin and Subcutaneous Tissue Disorders |
2
66.7%
|
2
50%
|
8
88.9%
|
| Alopecia |
2
66.7%
|
1
25%
|
8
88.9%
|
| Pruritus |
0
0%
|
2
50%
|
1
11.1%
|
| Musculoskeletal and Connective Tissue Disorders |
3
100%
|
2
50%
|
7
77.8%
|
| Myalgia |
2
66.7%
|
0
0%
|
6
66.7%
|
| Athralgia |
1
33.3%
|
2
50%
|
0
0%
|
| General Disorders & Administration Site Conditions |
3
100%
|
1
25%
|
5
55.6%
|
| Fatigue |
3
100%
|
0
0%
|
1
11.1%
|
| Investigations |
0
0%
|
2
50%
|
8
88.9%
|
| Weight increased |
0
0%
|
2
50%
|
7
77.8%
|
| Title | Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) |
|---|---|
| Description | The best overall response is the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], stable disease [SD], and progressive disease [PD]) among all overall responses from the start of treatment until the participant withdraws from the study. Participants who did not have a tumor assessment, the best overall response is Not Evaluable (NE). The response rate was defined as the proportion of participants with a best overall response of CR or PR, ie, [confirmed and unconfirmed, (CR + PR) / number of participants]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, CR was defined as the disappearance of all target lesions, PR was defined as ≥30% decrease in the sum of diameters of target lesions, PD was defined as ≥20 increase in the smallest sum of diameters, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Time Frame | Baseline up to Week 18 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Best overall response and objective response rate were assessed in the Efficacy Analysis Set. |
| Arm/Group Title | CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion | CS71017 0.5 mg BID; Initial and Additional Portion | Overall |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received 0.25 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.50 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.5 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. Cycle 1, Day 1: Carboplatin and paclitaxel only Cycle 1, Day 3: CS-7017 at the dose selected in initial portion Subsequent cycles: CS-7017 with carboplatin and paclitaxel | All participants who received 0.5 mg twice daily CS-7017 in combination with carboplatin and paclitaxel during either the initial or additional portion. | All participants who received CS-7017 in combination with carboplatin and paclitaxel. |
| Measure Participants | 3 | 3 | 8 | 11 | 14 |
| Complete response (CR) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Partial response (PR) |
0
0%
|
2
50%
|
4
44.4%
|
6
37.5%
|
6
NaN
|
| Stable disease (SD) |
1
33.3%
|
0
0%
|
2
22.2%
|
2
12.5%
|
3
NaN
|
| Progressive disease (PD) |
2
66.7%
|
1
25%
|
2
22.2%
|
3
18.8%
|
5
NaN
|
| Not evaluable (NE) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Missing |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Response rate (CR + PR) |
0
0%
|
2
50%
|
4
44.4%
|
6
37.5%
|
6
NaN
|
| Title | CS-7017-Related Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group After Administration of CS-7017 and Carboplatin/Paclitaxel in Chemotherapy-naïve Participants With Stage IIIb/IV Non-small Cell Lung Cancer |
|---|---|
| Description | Treatment-emergent adverse events (TEAEs) are defined as those adverse events that occur, having been absent before the study, or worsen in severity after the initiation of study drug. CS-7017-related TEAEs are those TEAEs that are related to CS-7017 in the relationship. |
| Time Frame | Baseline to 30 days after last dose, up to approximately 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| CS-7017-related TEAEs were assessed in the Safety Analysis Set. |
| Arm/Group Title | CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion |
|---|---|---|---|
| Arm/Group Description | Participants who received 0.25 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.50 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.5 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. Cycle 1, Day 1: Carboplatin and paclitaxel only Cycle 1, Day 3: CS-7017 at the dose selected in initial portion Subsequent cycles: CS-7017 with carboplatin and paclitaxel |
| Measure Participants | 3 | 4 | 9 |
| At least one CS-7017-related TEAE |
2
66.7%
|
3
75%
|
8
88.9%
|
| Respiratory, Thoracic and Mediastinal Disorders |
0
0%
|
1
25%
|
4
44.4%
|
| Pleural effusion |
0
0%
|
1
25%
|
4
44.4%
|
| General Disorders & Administration Site Conditions |
1
33.3%
|
2
50%
|
7
77.8%
|
| Face oedema |
1
33.3%
|
2
50%
|
4
44.4%
|
| Oedema peripheral |
0
0%
|
2
50%
|
3
33.3%
|
| Investigations |
1
33.3%
|
3
75%
|
8
88.9%
|
| Weight increased |
1
33.3%
|
3
75%
|
8
88.9%
|
Adverse Events
| Time Frame | Treatment-emergent adverse event data were collected from baseline to 30 days after last dose, up to approximately 1 year. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events were 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. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug. | |||||
| Arm/Group Title | CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion | |||
| Arm/Group Description | Participants who received 0.25 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.50 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. | Participants who received 0.5 mg twice daily (BID) CS-7017 combination treatment administered orally. Paclitaxel was administered intravenously at a dose of 200 mg/m^2 over 3 hours immediately after administration of CS-7017. Carboplatin was administered intravenously. The dose of the carboplatin was calculate using Calvert formula and target area under the plasma concentration-time curve (AUC) of 6 mg/mL*min. Cycle 1, Day 1: Carboplatin and paclitaxel only Cycle 1, Day 3: CS-7017 at the dose selected in initial portion Subsequent cycles: CS-7017 with carboplatin and paclitaxel | |||
All Cause Mortality |
||||||
| CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 1/4 (25%) | 0/9 (0%) | |||
Serious Adverse Events |
||||||
| CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 1/4 (25%) | 6/9 (66.7%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 1/3 (33.3%) | 0/4 (0%) | 2/9 (22.2%) | |||
| Cardiac disorders | ||||||
| Pericardial effusion | 1/3 (33.3%) | 0/4 (0%) | 0/9 (0%) | |||
| General disorders | ||||||
| Pyrexia | 0/3 (0%) | 0/4 (0%) | 2/9 (22.2%) | |||
| Chest pain | 0/3 (0%) | 0/4 (0%) | 1/9 (11.1%) | |||
| Infections and infestations | ||||||
| Pneumonia klebsiella | 0/3 (0%) | 0/4 (0%) | 1/9 (11.1%) | |||
| Septic shock | 0/3 (0%) | 1/4 (25%) | 0/9 (0%) | |||
| Investigations | ||||||
| Weight increased | 0/3 (0%) | 0/4 (0%) | 1/9 (11.1%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/3 (0%) | 0/4 (0%) | 1/9 (11.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pleural effusion | 0/3 (0%) | 0/4 (0%) | 2/9 (22.2%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| CS-7017 0.25 mg BID; Initial Portion | CS-7017 0.50 mg BID; Initial Portion | CS-7017 0.50 mg BID; Additional Portion | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 4/4 (100%) | 9/9 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Neutropenia | 3/3 (100%) | 3/4 (75%) | 9/9 (100%) | |||
| Anaemia | 2/3 (66.7%) | 3/4 (75%) | 8/9 (88.9%) | |||
| Thrombocytopenia | 2/3 (66.7%) | 3/4 (75%) | 7/9 (77.8%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 3/3 (100%) | 2/4 (50%) | 8/9 (88.9%) | |||
| Constipation | 1/3 (33.3%) | 1/4 (25%) | 4/9 (44.4%) | |||
| General disorders | ||||||
| Asthenia | 2/3 (66.7%) | 2/4 (50%) | 7/9 (77.8%) | |||
| Fatigue | 3/3 (100%) | 1/4 (25%) | 4/9 (44.4%) | |||
| Face oedema | 1/3 (33.3%) | 2/4 (50%) | 4/9 (44.4%) | |||
| Oedema peripheral | 0/3 (0%) | 2/4 (50%) | 3/9 (33.3%) | |||
| Infections and infestations | ||||||
| Upper respiratory tract infection | 2/3 (66.7%) | 0/4 (0%) | 0/9 (0%) | |||
| Investigations | ||||||
| Weight increased | 1/3 (33.3%) | 3/4 (75%) | 8/9 (88.9%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 2/3 (66.7%) | 3/4 (75%) | 7/9 (77.8%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Myalgia | 2/3 (66.7%) | 3/4 (75%) | 6/9 (66.7%) | |||
| Athralgia | 1/3 (33.3%) | 3/4 (75%) | 0/9 (0%) | |||
| Nervous system disorders | ||||||
| Neuropathy peripheral | 3/3 (100%) | 2/4 (50%) | 9/9 (100%) | |||
| Dizziness | 3/3 (100%) | 1/4 (25%) | 2/9 (22.2%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pleural effusion | 0/3 (0%) | 1/4 (25%) | 5/9 (55.6%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 2/3 (66.7%) | 1/4 (25%) | 9/9 (100%) | |||
| Pruritus | 0/3 (0%) | 2/4 (50%) | 1/9 (11.1%) | |||
| Rash | 0/3 (0%) | 2/4 (50%) | 0/9 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Contact for Clinical Trial Information |
|---|---|
| Organization | Daiichi Sankyo |
| Phone | 908-992-6400 |
| CTRinfo@dsi.com |
Responsible Party:
Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01199055
Other Study ID Numbers:
- CS7017-A-A108
First Posted:
Sep 10, 2010
Last Update Posted:
Jul 7, 2020
Last Verified:
Jun 1, 2020