E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with advanced non-small-cell lung cancer who have received at least two lines of prior chemotherapy |
|
E.1.1.1 | Medical condition in easily understood language |
patients with advanced lung cancer who have received previous
chemotherapies |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066490 |
E.1.2 | Term | Progression of non-small cell lung cancer |
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 | 14.1 |
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 estimate efficacy for each study strata at 18 weeks as assessed by RECIST
The following strata will be assigned:
1. Patients with EGFR activating mutation tumors
2. Patients with KRAS mutant tumors
3. Patients with EML4-ALK translocations
4. Patients with EGFR wt and KRAS wt tumors
5. Modified stratum for patients with EGFR activating mutation tumors |
|
E.2.2 | Secondary objectives of the trial |
- To estimate overall survival (OS) and progression free survival (PFS) in patients with
advanced NSCLC receiving AUY922.
- To determine safety and tolerability of AUY922 i.v. monotherapy in advanced NSCLC
patients.
- To assess the pharmacokinetics (PK) profile of AUY922 in NSCLC patients.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with histologically or cytologically confirmed advanced (stage
IIIB or stage IV) NSCLC who have received at least two prior lines of
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treatment. Patients who, in the investigators opinion, are deemed
unsuitable for the standard 2nd line chemotherapy will be eligible for
protocol participation. One of the prior lines must have included a
platinum agent. Prior treatment with a platinum agent is not a
requirement for EGFR mutant patients and patients with EML4-ALK
translocations.
• Patients enrolled to the fifth stratum, modified EGFR mutant, must
have documented prior response to EGFR TKI as defined by CR, PR or SD
for 6 months or greater unless patient has de novo resistance to EGFR
TKI (e.g. exon 20 insertions.) • All patients must have at least one measurable lesion as defined by
RECIST criteria. Previously irradiated lesions are not measurable unless
the lesion is new or has demonstrated clear progression after radiation.
• World Health Organization (WHO) performance status ≤ 2. For patients
enrolled to the fifth stratum, modified EGFR mutant, World Health
Organization (WHO) performance status ≤ 1.
• Patients enrolled to the fifth stratum, modified EGFR mutant, must be
willing and suitable to undergo fresh baseline biopsy prior to study
treatment (unless patient had recent biopsy after EGFR TKI progression
that concluded resistance to EGFR TKI.)
• Hematologic:
o Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L.
o Hemoglobin (Hgb) ≥ 9 g/dl.
o Platelets (plt) ≥ 100 x 109/L.
• Biochemistry:
o Total calcium (corrected for serum albumin) within normal limits or
correctable with supplements.
o Magnesium within lower normal limits or correctable with
supplements.
• Adequate liver function defined as:
o AST/SGOT and ALT/SGPT ≤ 3.0 x Upper limit of Normal (ULN) or ≤
5.0 x ULN if liver metastasis are present.
o Serum bilirubin ≤ 1.5 x ULN.
o Serum albumin > 2.5 g/dL.
o Serum creatinine ≤ 1.5 x ULN or 24 hour clearance ≥ 50 mL/mi
Other protocol-defined inclusion criteria may apply |
|
E.4 | Principal exclusion criteria |
• Patients who have received more than four lines of prior treatment.
Exception: Patients enrolled to the fifth stratum, modified EGFR mutant,
must not have received more than two prior lines of therapy.
Chemotherapy administered as adjuvant treatment more than six
months prior to study enrollment is not considered a prior line of therapy
for purposes of this study.
• Patients with a history of CNS metastasis. Note: Patients without
clinical signs and symptoms of CNS involvement are not required to have
MRI of the brain. Exception: Patients with treated brain metastases who
are asymptomatic, who has discontinued corticosteroids, and who have
been clinically stable for one month will be eligible for protocol
participation. This exception is not valid for patients enrolled to the fifth
stratum, modified EGFR mutant. These patients must not have CNS
involvement.
• Prior anti-neoplastic treatment with any HSP90 or HDAC inhibitor
compound.
• Patients must not have received:
o any systemic anti-cancer treatment or radiotherapy within 4 weeks
prior to first dose of study treatment and should have recovered to
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baseline or less than Grade 1 from toxicities of such therapy prior to the
first dose of study treatment
o 2 weeks for palliative radiotherapy to bones, 6 weeks for nitrosoureas
and mitomycin
o 4 weeks for monoclonal antibodies
o and ≤5 half-life of the agent or active metabolities [if any] for
continuous systemic anti-cancer treatment or investigational
• Patients who do not have either an archival tumor sample available or
are unwilling to have a fresh tumor sample collected at baseline
Other protocol-defined exclusion criteria may apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy as assessed by RECIST, to be classified as response (complete or partial), stable disease at 18 weeks, or no clinical benefit (NCB) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Efficacy; OS, PFS as assessed by RECIST.
• Safety parameters: Adverse drug reactions and serious adverse drug
reactions, changes in hematology and chemistry values, including those
associated with hepatic and renal function, and assessment of physical
examinations, vital signs, ocular symptoms and cardiac function (i.e.
repeated electrocardiograms). CTCAE version 4.0 will be used.
• Pharmacokinetics: Exposure of AUY922 in plasma. Parameters
assessed include AUC, Cmax, Tmax, CL, and Vz.
Additional secondary endpoints as defined in the protocol |
|
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 | 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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Canada |
France |
Germany |
Korea, Republic of |
Netherlands |
Norway |
Singapore |
Spain |
|
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
|
End of study is defined as the time when a patients is discontinued permanently from any study evaluation (including survival data collection).
The End of trial has occured when the last patient has been followed 1 year for survival after last visit of the last patient. |
|
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 | 3 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |