A Study of AUY922 in Non-small-cell Lung Cancer Patients Who Have Received Previous Two Lines of Chemotherapy.

NCT ID: NCT01124864

Last Updated: 2016-03-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2014-08-31

Brief Summary

This study will assess the efficacy of AUY922, when administered weekly at 70 mg/m2, in adult patients with advanced Non-small-cell Lung Cancer (NSCLC), who have received at least two prior lines of chemotherapy. Patients will be retrospectively, and prospectively, stratified based on their molecular tumor etiology. The following strata was assigned: Patients with Epidermal growth factor receptor (EGFR) activating mutations, Patients with Kirstin Raus sarcoma virus (KRAS) activating mutations, Patients with EML4-ALK (anaplastic lymphoma kinase) translocations and patients that were both EGFR and Kras wild type.

Conditions

Non-small-cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

EGFR mutant patients

Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.

Group Type: EXPERIMENTAL

AUY922

Intervention Type: DRUG

AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.

Kras mutant patients

Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.

Group Type: EXPERIMENTAL

AUY922

Intervention Type: DRUG

AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.

EGFR and Kras wild type patients

Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.

Group Type: EXPERIMENTAL

AUY922

Intervention Type: DRUG

AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.

Patients with EML4-ALK translocation

Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.

Group Type: EXPERIMENTAL

AUY922

Intervention Type: DRUG

AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.

Modified EGFR mutant patients

The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions.

Group Type: EXPERIMENTAL

AUY922

Intervention Type: DRUG

AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.

Interventions

AUY922

AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with histologically or cytologically confirmed advanced (stage IIIB or stage IV) NSCLC who have received at least two prior lines of 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:

• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L.
• Hemoglobin (Hgb) ≥ 9 g/dl.
• Platelets (plt) ≥ 100 x 109/L.

Biochemistry:

• Total calcium (corrected for serum albumin) within normal limits or correctable with supplements.
• Magnesium within lower normal limits or correctable with supplements.

Adequate liver function defined as:

• AST/SGOT and ALT/SGPT ≤ 3.0 x Upper limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastasis are present.
• Serum bilirubin ≤ 1.5 x ULN.
• Serum albumin > 2.5 g/dL.
• Serum creatinine ≤ 1.5 x ULN or 24 hour clearance ≥ 50 mL/min.

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:

• any systemic anti-cancer treatment or radiotherapy within 4 weeks prior to first dose of study treatment and should have recovered to baseline or less than Grade 1 from toxicities of such therapy prior to the first dose of study treatment
• 2 weeks for palliative radiotherapy to bones, 6 weeks for nitrosoureas and mitomycin
• 4 weeks for monoclonal antibodies
• and ≤5 half-life of the agent or active metabolites [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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

University of California at Los Angeles UCLA - Santa Monica

Los Angeles, California, United States

Maryland Oncology Hematology, P.A. Dept. of Assoc. Onc/Hem

Rockville, Maryland, United States

Dana Farber Cancer Institute DFCI

Boston, Massachusetts, United States

St. Luke's Hospital and Health Network St Luke's

Bethlehem, Pennsylvania, United States

Novartis Investigative Site

Edmonton, Alberta, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Créteil, , France

Novartis Investigative Site

Marseille, , France

Novartis Investigative Site

Villejuif, , France

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Oldenburg, , Germany

Novartis Investigative Site

Amsterdam, , Netherlands

Novartis Investigative Site

Groningen, , Netherlands

Novartis Investigative Site

Oslo, , Norway

Novartis Investigative Site

Singapore, Singapore, Singapore

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Badalona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Izmir, Turkey, Turkey (Türkiye)

Countries

United States; Canada; France; Germany; Netherlands; Norway; Singapore; South Korea; Spain; Turkey (Türkiye)

References

Felip E, Barlesi F, Besse B, Chu Q, Gandhi L, Kim SW, Carcereny E, Sequist LV, Brunsvig P, Chouaid C, Smit EF, Groen HJM, Kim DW, Park K, Avsar E, Szpakowski S, Akimov M, Garon EB. Phase 2 Study of the HSP-90 Inhibitor AUY922 in Previously Treated and Molecularly Defined Patients with Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2018 Apr;13(4):576-584. doi: 10.1016/j.jtho.2017.11.131. Epub 2017 Dec 13.

Reference Type: DERIVED

PMID: 29247830 (View on PubMed)

Other Identifiers

2010-020116-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAUY922A2206

Identifier Type: -

Identifier Source: org_study_id