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

Phase 1

Completed

Conditions: Carcinoma, Non-Small-Cell Lung

Interventions: Drug: CS-7017
Drug: Erlotinib

Registration Number: NCT01199068

Lead Sponsor: Daiichi Sankyo Co., Ltd.

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 erlotinib, and to assess the pharmacokinetics of CS-7017 in combination with erlotinib.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

Inclusion Criteria

Histologically or cytologically confirmed unresectable locally advanced or metastatic (stage IIIb or IV) Non-small Cell Lung Cancer (NSCLC)
Recurrent disease (either no response to treatment or subsequent relapse after an objective response) that has progressed after first-line platinum based therapy
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

Prior Tyrosine Kinase Inhibitor (TKI) therapy
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
Treatment with anticancer medication within 4 weeks before study treatment, currently enrolled in another investigational drug study, or enrolled in another investigational drug study within 4 weeks of start of 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 (HBsAg)-, hepatitis C virus (HCV)- or human immunodeficiency virus (HIV)-positive or 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 Thiazolidinedione(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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CS-7017+Erlotinib	CS-7017	Drug: CS-7017 from 0.25 mg to 0.50 mg twice a daily Drug: Erlotinib 150 mg once daily
CS-7017+Erlotinib	Erlotinib	Drug: CS-7017 from 0.25 mg to 0.50 mg twice a daily Drug: Erlotinib 150 mg once daily

Primary Outcome Measures

Name	Time	Method
CS-7017-Related Treatment-Emergent Adverse Events Occurring During the Study of Administration of CS-7017 Combined With Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer Who Failed First-line Therapy	From post first dose to 30 days after last dose, up to approximately 1.5 years	A treatment-emergent adverse event (TEAE) is defined as any event not present prior to the initiation of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. A CS-7017-related TEAE is an TEAE that is related to CS7017 in the relationship.
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Serum Free Form of CS-7017 (R-150033) After CS-7017 and Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer	Cycle 1, Week 1 and Cycle 2, Week 4	After the first CS-7017 administration, area under the concentration-time curve from zero to the last quantifiable concentration (AUClast) and area under the concentration-time curve during dosing interval (AUCtau) were assessed.
Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Serum Free Form of CS-7017 (R-150033) After CS-7017 and Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer	Cycle 1, Week 1 and Cycle 2, Week 4	After the first CS-7017 administration, observed serum concentration (Cmax) and observed serum concentration at steady state (Cmax,ss) were assessed.
Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Serum Free Form of CS-7017 (R-150033) After CS-7017 and Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer	Cycle 1, Week 1 and Cycle 2, Week 4	After the first CS-7017 administration, time of maximum plasma concentration (Tmax) and time of maximum plasma concentration at steady state (Tmax,ss) were assessed.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival Time Following Administration of CS-7017 in Combination With Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) Who Failed First-line Therapy	From randomization to PD or death, up to approximately 1.5 years	Progression-free survival (PFS) was defined as the time from randomization to the date of the first objective documentation of progressive disease (PD) or death resulting from any cause, whichever came first.
Erlotinib-Related Treatment-Emergent Adverse Events Occurring During the Study of Administration of CS-7017 Combined With Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer Who Failed First-line Therapy	From post first dose to 30 days after last dose, up to approximately 1.5 years	A treatment-emergent adverse event (TEAE) is defined as any event not present prior to the initiation of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. An erlotinib-related TEAE is an TEAE that is related to erlotinib in the relationship
Best Overall Response and Response Rate Following Administration of CS-7017 in Combination With Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) Who Failed First-line Therapy	From screening and after completion of every 2 cycles (6 weeks) until disease progression, withdrawal of consent, death, or loss to follow-up, up to approximately 1.5 years	As per Response Evaluation Criteria for Solid Tumors v1.1, best overall response was characterized as complete response (CR) defined as disappearance of all target lesions, partial response (PR) defined as ≥30% decrease in the sum of diameters of target lesions, progressive disease (PD) defined as ≥20% increase in the sum of diameters of target lesions, and stable disease (SD) defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Response rate was defined as CR + PR.