CS-7017 in Combination With Carboplatin/Paclitaxel in Subjects With Stage IIIb/IV Non-small Cell Lung Cancer (NSCLC)

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)

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: CS-7017; Drug: Carboplatin; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gangnam-gu
    • Seoul, Gangnam-gu, Korea, Republic of, 135-710
      • Samsung Medical Center

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: CS7017; 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: Paraplatin; Drug: Paclitaxel; Drug: Paclitaxel IV, 200mg/m^2, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks); Other Names: Taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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).	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
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	The maximum serum concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D).	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
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	The time of maximum plasma concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D).	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
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	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.	Baseline to end of Cycle 1, with each treatment cycle being 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Baseline up to Week 18 postdose
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	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.	Baseline to 30 days after last dose, up to approximately 1 year

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.
• Collaborators: ICON Clinical Research

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: August 30, 2010
• First Submitted That Met QC Criteria: September 9, 2010
• First Posted (Estimate): September 10, 2010

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: June 23, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Cancer; Neoplasms; Carboplatin; Paclitaxel; Tumor; Respiratory Tract Neoplasms; PPAR gamma agonist; Antineoplastic Agent
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel; Efatutazone
• Other Study ID Numbers: CS7017-A-A108

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