Phase 1b Study of CS-7017 in Combination With Erlotinib in Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) Who Failed First-line Therapy
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Daiichi Sankyo Co., Ltd.
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- 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
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- 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)
- •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
Arms & Interventions
CS-7017+Erlotinib
Drug: CS-7017 from 0.25 mg to 0.50 mg twice a daily Drug: Erlotinib 150 mg once daily
Intervention: CS-7017 (Drug)
CS-7017+Erlotinib
Drug: CS-7017 from 0.25 mg to 0.50 mg twice a daily Drug: Erlotinib 150 mg once daily
Intervention: Erlotinib (Drug)
Outcomes
Primary Outcomes
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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)