Hsp90 Inhibitor AUY922 and Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer

NCT01259089 | Completed Phase 1 Results DMC

• 2 other identifiers: NU 10L01STU00038215
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

Hsp90 inhibitor AUY922 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase I/II trial is studying the side effects and best dose of Hsp90 inhibitor AUY922 when given together with erlotinib hydrochloride and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer.

Conditions

Adenocarcinoma of the Lung; Non-small Cell Lung Cancer

Keywords

Adenocarcinoma of the Lung; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I)

  To determine the maximally tolerated dose (MTD), and recommended phase II dose of AUY922 when given in combination with erlotinib for patients with acquired resistance to erlotinib. (Phase I) Escalation of dose will be in a 3+3 design. If no dose limiting toxicities (DLTs) are seen in 3 patients enrolled at that dose level, then dose will be escalated to the next dose level and the next 3 patients will be enrolled at that dose. Alternatively, if 1 DLT is seen in 3 patients at that dose level, 3 more patients will be added at that same dose level. If 1 DLT is seen in 6 patients at that dose level, MTD will be determined to be at that dose. If more than 1 DLT is seen at that dose level, then the prior lower dose level will be the considered the MTD. DLT is defined as any of the following related to the investigational agent: Death and grade 3 and 4 specific hematological and non-hematological toxicities defined in the protocol.

  During the first 4 weeks of treatment for each patient.

• Overall Response Rate (ORR), Defined as Complete Response(CR) + Partial Response (PR) Using the Modified RECIST 1.1 Criteria for All Patients Treated at Dose of 70mg/m2 AUG922

  Overall response rate (ORR) will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan or MRI: Complete response (CR) defined as disappearance of all target lesions. Partial Response (PR), defined as \>=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD) defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. Progressive Disease (PD) defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions

  At 8 weeks from treatment initiation

Secondary Outcomes (5)

• Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II)

  At weeks 1 through 4 and then every 2 weeks during treatment and 30 days post last treatment for up to 2 years and half years

• Incidence of Reported Adverse Events in Phase I

  At weeks 1 through 4 and then every 2 weeks during treatment and 30 days post last treatment, for up to 2 years and half years

• Progression-free Survival (Phase II)

  From the time of first treatment with AUY922 to disease progression for up to 2 years post treatment

• Overall Survival (Phase II)

  From the time of first treatment with AUY922 to death, followed up to 2 years post treatment

• Overall Survival Among Patients With Acquired Resistance With T790M Mutations (Phase II)

  From the time of first treatment with AUY922 to death, followed for up to 2 years

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive Hsp90 inhibitor AUY922 IV over 1 hour once weekly and oral erlotinib hydrochloride once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: erlotinib hydrochloride; Drug: Hsp90 inhibitor AUY922; Other: laboratory biomarker analysis; Procedure: needle biopsy; Genetic: mutation analysis; Other: pharmacological study

Interventions

erlotinib hydrochloride DRUG

Given orally

Also known as: CP-358,774, erlotinib, OSI-774, Tarceva

Arm I

Hsp90 inhibitor AUY922 DRUG

Given IV

Also known as: AUY922

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

needle biopsy PROCEDURE

Undergo image-guided needle biopsy (correlative studies)

Also known as: aspiration biopsy, puncture biopsy

Arm I

mutation analysis GENETIC

Correlative studies

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically at NU, MSKCC, or DFCI and EITHER previous RECIST-defined response (CR or PR) to an EGFR-TKI (erlotinib or gefitinib) or an investigational EGFR TK inhibitor OR a documented mutation in the EGFR gene (G719X, exon 19 deletion, L858R, L861Q)
• Radiographic progression by RECIST during treatment with erlotinib/gefitinib
• Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time
• Measurable (RECIST) indicator lesion not previously irradiated
• Must have undergone a biopsy after the development of acquired resistance
• Karnofsky Performance Status \>= 70% OR ECOG/WHO Performance Status 0-1
• Signed informed consent
• Effective contraception and negative serum pregnancy test obtained within two weeks prior to the first administration of AUY922 in all pre-menopausal women (ie., last menstrual period =\< 24 months ago) and women \< 2 years after onset of menopause; menopause is defined as the time at which fertility ceases, where a woman has had no menstruation for \> 24 months
• Total bilirubin =\< 1.5 x Upper Limit of Normal (ULN)
• AST/SGOT and ALT/SGPT =\< 3.0 x ULN, or =\< 5.0 x ULN if liver metastasis present
• Absolute neutrophil count (ANC) \>= 1.5 x10\^9/L
• Hemoglobin (Hgb) \>= 9g/dL
• Platelets (plts) \>= 100 x 10\^9/L
• Serum creatinine =\< 1.5 x ULN or 24 hour clearance \>= 50 mL/min

You may not qualify if:

• Symptomatic CNS metastases which are symptomatic and /or requiring escalating doses of steroids
• Prior treatment with any HSP90 inhibitor compounds
• Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed)
• Palliative radiation within 2 weeks
• Unresolved diarrhea \>= CTCAE grade 2
• Pregnant or lactating women
• Women of childbearing potential (WCBP) (i.e. women able to become pregnant) not using double-barrier methods of contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile); male patients whose partners are WCBP not using double-barrier methods of contraception
• Acute or chronic liver or renal disease
• Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol
• Major surgery =\< 2 weeks prior to randomization or who have not recovered from such therapy
• History (or family history) of long QT syndrome
• Mean QTc \>= 450 msec on baseline ECG
• History of clinically manifested ischemic heart disease =\< 6 months prior to study start
• History of heart failure or left ventricular (LV) dysfunction (LVEF =\< 45%) by MUGA or ECG
• Clinically significant resting bradycardia (\< 50 beats per minute)

Sponsors & Collaborators

• Northwestern University: lead
• Robert H. Lurie Cancer Center: collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Johnson ML, Yu HA, Hart EM, Weitner BB, Rademaker AW, Patel JD, Kris MG, Riely GJ. Phase I/II Study of HSP90 Inhibitor AUY922 and Erlotinib for EGFR-Mutant Lung Cancer With Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. J Clin Oncol. 2015 May 20;33(15):1666-73. doi: 10.1200/JCO.2014.59.7328. Epub 2015 Apr 13.

  PMID: 25870087 DERIVED

MeSH Terms

Conditions

Adenocarcinoma of Lung; Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; 5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; Biopsy, Needle

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures; Investigative Techniques

Limitations and Caveats

Data was collected up until September 30 2014 when study was closed permanently and no further data was collected for patients survival due to IND withdrawal.

Results Point of Contact

• Title: Clinical Trials Office
• Organization: Northwestern University

312-695-1301

Study Officials

• Melissa Johnson

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2010
• First Posted: December 13, 2010
• Study Start: April 27, 2011
• Primary Completion: June 4, 2013
• Study Completion: September 29, 2014
• Last Updated: September 11, 2019
• Results First Posted: November 21, 2018

Record last verified: 2018-10

Locations

US (2)