E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Squamous Cell Non-small cell lung cancer |
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E.1.1.1 | Medical condition in easily understood language |
A type of lung cancer involving a type of cells called squamous cells |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 evaluate progression free survival (PFS) with nab-paclitaxel as maintenance treatment after response or stable disease (SD) with nab-paclitaxel plus carboplatin in subjects with squamous cell NSCLC. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of nab-paclitaxel as maintenance treatment after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell NSCLC.
- To further assess the efficacy with nab-paclitaxel as maintenance treatment after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell NSCLC, as measured by secondary efficacy endpoints |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
General and Demographics
1. Age ≥ 18 years of age at the time of signing the ICF.
2. Understand and voluntarily provide written consent to the ICF prior to conducting any
study related assessments/procedures.
3. Able to adhere to the study visit schedule and other protocol requirements
Disease Specific
4. Histologically or cytologically confirmed Stage IIIB or IV squamous cell NSCLC at
study entry.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease at study entry (as defined by the
RECIST v1.1 criteria).
7. No prior chemotherapy for the treatment of metastatic NSCLC at study entry. Adjuvant, neo-adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease is permitted providing it was completed 12 months
prior to starting the study and without disease recurrence.
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3.
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]), alanine
transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limit of
normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 × ULN except in cases of Gilbert’s disease and liver metastases.
13. Creatinine ≤ 1.5 mg/dL.
14. Expected survival of > 12 weeks for the Induction part of the study.
15. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
16. For Maintenance part of the study, subjects must have received at least one dose of nabpaclitaxel
in each of the 4 cycles during Induction
Pregnancy
17. Females of childbearing potential [defined as a sexually mature woman who (1) have not
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for
at least 24 consecutive months (ie, has had menses at any time during the preceding 24
consecutive months)] must:
a. agree to take a pregnancy test prior to starting study medication and throughout the
study participation.
b. commit to complete abstinence from heterosexual contact, or agree to use medical
doctor-approved contraception throughout the study without interruption, and while
receiving study medication or for a longer period if required by local regulations.
Male subjects must:
c. agree to complete abstinence from heterosexual contact or use a condom during
sexual contact with a female of child bearing potential while receiving study
medication and within 6 months after last dose of study medication, even if he has
undergone a successful vasectomy.
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E.4 | Principal exclusion criteria |
1. Evidence of active brain metastases, including leptomeningeal involvement (prior
evidence of brain metastasis are permitted only if treated and stable and off therapy for ≥
4 weeks prior to first dose of study drug).
2. Only evidence of disease is non-measurable at study entry.
3. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per CTCAE v4.0). For the Maintenance part of the study subjects with peripheral neuropathy of Grade 3 and higher are excluded.
4. Venous thromboembolism (VTE) within 1 month prior to signing ICF. If the subject has a history of VTE earlier than 1 month prior to signing the ICF the event should be resolved, stable and without clinically significant bleeding, such as hematuria, gastrointestinal bleeding or hemoptysis.
5. Current congestive heart failure (New York Heart Association class II-IV).
6. History of the following within 6 months prior to first administration of a study drug: a
myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass
graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled
hypertension, clinically significant cardiac dysrhythmia or clinically significant ECG
abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
7. Treatment with any investigational product within 28 days prior to signing ICF.
8. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin.
9. Currently enrolled in any other clinical protocol or investigational trial that involved
administration of experimental therapy and/or therapeutic devices.
10. Any other clinically significant medical condition and/or organ dysfunction that will
interfere with the administration of the therapy according to this protocol.
11. Subject has any other malignancy within 5 years prior to randomization. Exceptions are malignancies with a negligible risk of metastasis or death (eg, expected 5-year OS > 90%) that were treated with an expected curative outcome such as squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin cancer, carcinoma in situ of the breast, or incidental histological finding of prostate cancer (TNM stage of T1a or T1b) — all treatments that should have been completed 6 months prior to signing ICF.
12. Subject has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2
weeks prior to starting IP, and/or from whom ≥ 30% of the bone marrow was irradiated.
Prior radiation therapy to a target lesion is permitted only if there has been clear
progression of the lesion since radiation was completed.
13. Any condition, including the presence of laboratory abnormalities, that places the subject
at unacceptable risk if he/she were to participate in the study.
14. Any condition that confounds the ability to interpret data from the study.
15. Pregnant and nursing females. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival from randomization into the Maintenance part of the study. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS, will be based on investigator’s assessment of response using RECIST 1.1 guidelines at baseline, end of cycle 2 and end of cycle 4 in Induction part, every 42 days during the Maintenance part of the study, and at end of treatment. Time to Progression will be calculated from the date of randomization (start of Maintenance part) to the first date of progressive disease or death from any cause.) |
|
E.5.2 | Secondary end point(s) |
Key secondary efficacy endpoints include OS, ORR, PFS and Disease Control Rate; safety parameters; time and duration of response; exploratory endpoints (please refer to these are outlined in the protocol on page 25) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key secondary efficacy endpoints include Overall Survial from randomization into the Maintenance part of the study. Overall Response Rate during the Induction and Maintenance part of the study. PFS from Day 1 Cycle 1. OS from Day 1 Cylce 1. ORR in Maintenance Part beyond response in Induction Part. Disease control rate during the Induction Part and over entire study. Time to response during Induction Part and over the entire study, with and without the requirement of confirmation of response. Duration of response over the entire study, with and without the requirement of confirmation of response. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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 |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Greece |
Italy |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 5 |
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 |