E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of patients with advanced non-small cell lung cancer (NSCLC) after failure of prior chemotherapy regimen |
|
E.1.1.1 | Medical condition in easily understood language |
Cancer of the colon and rectum (colorectal cancer) can invade and damage tissues and organs. Tumors of the colon/ rectum are growths of the inner wall of the large intestine. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To estimate the difference in efficacy, as measured by progression-free survival (PFS), between erlotinib in combination with CS-7017 and erlotinib alone. |
|
E.2.2 | Secondary objectives of the trial |
To estimate the overall survival (OS) in the two treatment arms.
To estimate the overall response rate (ORR) in the two treatment arms.
To estimate plasma concentration of CS-7017 at scheduled times points.
To evaluate the safety profile of the combination of CS-7017 and erlotinib relative to that of erlotinib alone. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must satisfy all of the following criteria to be included in the study:
1. Histologically or cytologically confirmed stage IIIB or IV NSCLC previously treated with a platinum-based regimen.
2. Progressive disease (either no response to treatment or subsequent relapse after an objective response) after the last anti-cancer therapy.
3. Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 criteria.
4. ≥ 18 years of age
5. ECOG performance status of 0, 1, or 2.
6. Adequate organ and bone marrow function as assessed by clinical laboratory evaluations:
- Hemoglobin ≥ 9 g/L
- Absolute neutrophil count ≥ 1.5 x 10e9/L
- Platelets ≥ 100 x 10e9 /L
- Serum creatinine <1.5 upper limit of normal (ULN) or calculated
creatinine clearance > 60 mL/min
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase < 2.5 x ULN if liver metastases are absent or ≤ 5.0 x ULN if liver metastases are present
- Total bilirubin ≤1.5 x ULN
7. Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, Version 4.0, grade ≤ 1 (see Section 17.2).
8. Women of childbearing potential must be willing to consent to using effective contraception (eg, hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device) while on treatment and for at least 3 months thereafter. Men who are the partner of a woman of childbearing potential must be willing to consent to using effective contraception (eg, vasectomy or barrier with spermicide) while on treatment and for 3 months thereafter.
9. All female subjects of childbearing potential must have a negative serum or urine pregnancy test result before initiating study treatment.
10. 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- or IRB-approved ICF (including HIPAA authorization, if applicable) before performance of any study-specific procedures or tests.
11. Subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
|
E.4 | Principal exclusion criteria |
Subjects who meet any of the following criteria will be disqualified from entering the study:
1. More than two prior chemotherapy regimens for advanced disease. Maintenance
therapy does not count as a separate regimen, if it is given after first line therapy
without intervening disease progression.
2. Prior treatment with EGFR inhibitors.
3. Treatment with anticancer therapy within 3 weeks before study treatment.
4. Therapeutic or palliative radiation therapy within 2 weeks or major surgery within
4 weeks before study treatment.
5. Prior administration of other TZDs within 4 weeks before study treatment or current need for concomitant use of other TZDs during the study.
6. Clinically active brain metastases, defined as untreated symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms; uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis. Subjects with treated brain metastases which are no longer symptomatic and require no treatment may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 15 days must have elapsed between the end of radiotherapy and study enrollment.
7. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection at time of screening.
8. History of any of the following conditions within 6 months before initiating study treatment: diabetes mellitus requiring treatment with insulin or TZD agents; myocardial infarction with significant impairment of cardiac function; severe/unstable angina pectoris; coronary/peripheral artery bypass graft; New York Heart Association (NYHA) class III or IV congestive heart failure; malabsorption syndrome, chronic diarrhea (lasting > 4 weeks), inflammatory bowel disease, or partial bowel obstruction.
9. Pericardial effusion or pericardial involvement with the tumor. Clinically significant pleural effusion (ie, requiring drainage). Subjects with minimal pleural effusion may be eligible upon request by Investigator and approval by Sponsor.
10. History of malignancy other than NCSLC, except adequately treated
non melanoma skin cancer, curatively treated in-situ cancer of the cervix or other
solid tumors curatively treated with no evidence of disease for ≥ 5 years.
11. Previous administration of CS-7017.
12. Pregnant or breast feeding.
13. 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.
14. Known hypersensitivity to any of the two study drugs.
15. Subjects currently enrolled in another investigational drug study or within
4 weeks of start of treatment. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is PFS. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
For progression free survival, we will evaluate whole Kaplan-Meier curve over time, not Kaplan-Meier curve at some specific timepoint. |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints are OS, ORR, safety endpoints of adverse events (AEs), clinical laboratory evaluations, physical examination findings, and vital sign measurements, and plasma concentrations of CS-7017. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
For overall survival, we will evaluate whole Kaplan-Meier curve over time, not Kaplan-Meier curve at some specific timepoint. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
The MP Erlotinib alone, without CS-7017 |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
India |
Korea, Republic of |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |