| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| In 2nd Line Subjects with Targeted Mutations (KRAS, NRAS, BRAF, MEK1) in Locally Advanced or Metastatic Nonsmall Cell Lung Cancer (NSCLC Stage IIIBwet-IV). |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | PT |
| E.1.2 | Classification code | 10059515 |
| E.1.2 | Term | Non-small cell lung cancer metastatic |
| 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 compare Progression-Free Survival (PFS) in KRAS mutated NSCLC subjects who are receiving GSK1120212 with those receiving docetaxel. |
|
| E.2.2 | Secondary objectives of the trial |
- To assess the safety and tolerability of GSK1120212 in NSCLC.
- To compare the response rate of subjects receiving GSK1120212 to those treated with docetaxel.
- To compare the duration of response of subjects receiving GSK1120212 to those treated with docetaxel.
-To estimate overall survival (OS).
-To assess the steady state exposure and characterise the population pharmacokinetics of GSK1120212. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Signed written informed consent.
2. 18 years old or older.
3. Histologically- or cytologically-confirmed diagnosis of adenocarcinoma Stage
IIIBwet (with confirmed malignant pleural effusion) or Stage IV NSCLC with a
positive mutational status for the KRAS, NRAS, BRAF, or MEK1 gene (performed
in a CLIA-certified laboratory or equivalent). View page page 27 of the protocol for further information.
4. Documented tumor progression (based on radiological imaging) after receiving at least one, but not more than one, prior approved platinum-containing chemotherapy regimen for advanced stage/metastatic NSCLC.
a. Erlotinib maintenance therapy following first-line treatment with any approved
platinum-containing chemotherapy for advanced stage/metastatic NSCLC is allowed.
b. Pemetrexed maintenance therapy is only allowed following a first-line treatment
with cisplatin or carboplatin and pemetrexed for advanced stage/metastatic
NSCLC.
c. Patients who have received any treatment (e.g., erlotinib, chemotherapy, or
Investigational Agents) in a second-line setting are not allowed.
5. Measurable disease, i.e., presenting with at least one measurable tumor lesion per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
6. Performance status score of 0 or 1 according to the Eastern Cooperative Oncology
Group (ECOG) scale.
7. Able to swallow and retain orally administered medication and does not have any
clinically significant gastrointestinal abnormalities that may alter absorption such as expectancy of at least three months in the opinion of the investigator.
8. Women of childbearing potential must have a negative serum pregnancy test within 14 days of randomization to study treatment and agree to use effective contraception, as defined in the protocol, during the study and for at least four weeks following the last dose of study medication. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described in the protocol from the time of randomization to study medication until at least four weeks after the last dose of study treatment. However, the Sponsor advises that contraception be used for a total of 16 weeks following the last dose (based on the lifecycle of sperm). Investigators should reference the product label for docetaxel for additional clarification.
9. Adequate baseline organ function as defined in Table 2.
10. French subjects: In France, a subject will be eligible for inclusion in this study only
if either affiliated to or a beneficiary of a social security category.
|
|
| E.4 | Principal exclusion criteria |
1. History of another malignancy. Exception: (a) history of curatively treated
malignancy different from NSCLC with a disease-free period of ≥ 3 years, (b)
history of completely resected non-melanoma skin cancer, (c) successfully treated in
situ carcinoma, (d) CLL in stable remission (Rai Stage 0) with no therapy required,
(e) indolent prostate cancer requiring no or only anti-hormonal therapy with
histologically confirmed tumor lesions that can be clearly differentiated from
NSCLC target and non-target lesions.
2. Any serious and/or unstable pre-existing medical disorder (aside from malignancy
exception above), psychiatric disorder, or other conditions that could interfere with
subject’s safety, obtaining informed consent or compliance to the study procedures,
in the opinion of the Investigator.
3. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to
drugs chemically related to study drugs, excipients, dimethyl sulfoxide (DMSO), or
to polysorbate 80.
4. Treatment with a BRAF or MEK inhibitor or docetaxel as monotherapy or as part of
a combination regimen.
5. Anti-cancer therapy (including chemotherapy and radiation therapy) within the last
three weeks.
6. Current use of a prohibited medication (see Section 6.2 titled Prohibited Medications and Non-Drug Therapies). Use of anticoagulants such as warfarin is permitted (see Section 6.1 title Permitted Mediations of the protocol), however INR must be monitored in
accordance with local institutional practice.
7. History or current evidence / risk of retinal vein occlusion (RVO) or central serous
retinopathy (CSR):
- History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled
glaucoma or ocular hypertension, uncontrolled systemic disease such as
hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability
syndromes).
- Visible retinal pathology as assessed by ophthalmic exam that is considered a risk
factor for RVO or CSR such as: Evidence of new optic disc cupping; Evidence of
new visual field defects; Intraocular pressure > 21 mm Hg as measured by
tonography.
8. Any tumor manifestation in the CNS.
9. History or evidence of cardiovascular risk including any of the following:
a. QTcB ≥ 480 msec.
b. History or evidence of current clinically significant uncontrolled arrhythmias.
Exception: Subjects with controlled atrial fibrillation for >30 days prior to
randomization are eligible.
c. History of acute coronary syndromes (including myocardial infarction and
unstable angina), coronary angioplasty, or stenting within 6 months prior to
randomization.
d. History or evidence of current ≥ Class II congestive heart failure as defined by
New York Heart Association (Appendix 4).
10. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or
Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV
and HCV infection which will be allowed).
11. French subjects: the French subject has participated in any study using an
investigational drug during the previous 30 days. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Clinical laboratory parameters, adverse events, cardiac parameters, and vital signs.
- Response rate defined as the percentage of subjects with evidence of complete response (CR) or partial response (PR) (RECIST 1.1).
- Duration of Response, for the subset of subjects with CR or PR, defined as the time from first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause.
- OS defined as the time from randomization until death.
- GSK1120212 trough concentrations and population PK parameters. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| 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 | Yes |
| 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 | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| 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 |
| France |
| Germany |
| Greece |
| Italy |
| Netherlands |
| Spain |
| 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
|
| Study will be closed when 80% of the randomized KRAS-mutant NSCLC subjects (96 subjects) have died, withdrawn, or are lost to follow-up. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| 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 | 1 |
| 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 |
Print
