Pemetrexed Disodium and Hsp90 Inhibitor AUY922 in Treating Patients With Previously Treated Stage IV Non-Small Cell Lung Cancer

NCT01784640 | Completed Phase 1 DMC

• 3 other identifiers: 12-001489NCI-2013-00410L-05
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and the best dose of Hsp90 inhibitor AUY922 when given together with pemetrexed disodium in treating patients with previously treated stage IV non-small cell lung cancer. Hsp90 inhibitor AUY922 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cell, either by killing the cells or stopping them from dividing. Giving Hsp90 inhibitor AUY922 together with pemetrexed disodium may kill more tumor cells

Conditions

Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (AEs) as assessed by National Cancer Institute (NCI) CTCAE version 4.0

  Safety will be assessed through tabulation, grading and attribution of serious adverse events (SAEs) and AEs.

  Up to 30 days after completion of study treatment

Secondary Outcomes (1)

• Tumor response rate according to RECIST version 1.1

  Up to 30 days after completion of study treatment

Study Arms (1)

Treatment (Hsp90 inhibitor AUY922, pemetrexed disodium)

EXPERIMENTAL

Patients receive Hsp90 inhibitor AUY922 IV over 60 minutes weekly and pemetrexed disodium IV over 15 minutes every 3 weeks. Courses repeat every 21 days for 6 months in the absence of disease progression or unacceptable toxicity.

Drug: Hsp90 inhibitor AUY922; Drug: pemetrexed disodium; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

Hsp90 inhibitor AUY922 DRUG

Given IV

Also known as: AUY922

Treatment (Hsp90 inhibitor AUY922, pemetrexed disodium)

pemetrexed disodium DRUG

Given IV

Also known as: ALIMTA, LY231514, MTA

Treatment (Hsp90 inhibitor AUY922, pemetrexed disodium)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (Hsp90 inhibitor AUY922, pemetrexed disodium)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (Hsp90 inhibitor AUY922, pemetrexed disodium)

Eligibility Criteria

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

You may qualify if:

• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations
• Histologically- or cytologically-confirmed stage IV non-squamous, NSCLC who have progressed after at least one prior line of treatment; in the expansion phase, participants are only eligible if their molecular category has not been fully enrolled (10 participants with epidermal growth factor receptor (EGFR) mutations, 5 participants with anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangement, 5 participants with wild type v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), EGFR and ALK)
• At least one measurable lesion as defined by modified RECIST version 1.1; previously irradiated lesions are not measurable unless the lesion is new or has demonstrated clear progression after radiation
• Last chemotherapy or treatment with another systemic anti-cancer agent must have stopped \>= 4 weeks prior to enrollment (or \>= 5 half-lives for oral tyrosine-kinase inhibitors or 2 weeks for palliative radiotherapy); participants must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] =\< 1 or baseline) from acute toxicities of any previous therapy (with the exception of alopecia)
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Expected survival time of \>= 3 months in the opinion of the investigator
• Absolute neutrophil count (ANC) \>=1.5 x 10\^9/L
• Hemoglobin (Hgb) \>= 9 g/dl
• Platelets (plt) \>= 100 x 10\^9/L
• Potassium within normal limits
• Total calcium (corrected for serum albumin) within normal limits or corrected with supplements
• Magnesium within lower limits or corrected with supplements
• Phosphorus within lower limits or corrected with supplements
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =\< 1.5 x upper limit of normal (ULN)
• AST/SGOT and ALT/SGPT =\< 2.5 x upper limit of normal (ULN) if liver metastases are present

You may not qualify if:

• Unresolved diarrhea \>= CTCAE (v4.0) grade 1
• Pregnant or lactating women
• Fertile women of childbearing potential (WCBP) not using (or refusing to use) adequate methods of contraception as agreed on between her and the consenting investigator; male participants not using (or refusing to use) a condom during intercourse
• History of another primary cancer within 3 years prior to enrollment with the exception of curatively treated skin cancer (other than melanoma) or curatively treated cervical carcinoma in-situ
• History of central nervous system (CNS) metastasis; Note: participants without clinical signs and symptoms of CNS involvement are not required to have magnetic resonance imaging (MRI) of the brain; (exception: participants with treated brain metastases who are asymptomatic, not currently on steroid therapy, and clinically stable for \>= 2 weeks will be eligible for protocol participation)
• Prior treatment with pemetrexed
• Prior anti-neoplastic treatment with any heat shock protein 90 (HSP90) or histone deacetylase (HDAC) inhibitor compound
• Participants who have undergone any major surgery =\< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Last chemotherapy or treatment with another systemic anti-cancer agent must have stopped \>= 4 weeks prior to enrollment (or \>= 5 half-lives for oral tyrosine-kinase inhibitors); participants with EGFR mutations and ALK gene rearrangement who have not received a tyrosine kinase inhibitor targeting their molecular abnormality (e.g., erlotinib or crizotinib respectively); participants must have recovered (CTCAE =\< 1) from acute toxicities of any previous therapy (with the exception of alopecia)
• Participants who have concurrent or uncontrolled illness that the investigator feels will impede study participation including, but not limited to:
• Acute or chronic liver disease
• Acute or chronic renal disease
• Active or ongoing infection
• Psychiatric illness/social situations that would limit compliance with study requirements
• Participants with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome)

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Translational Research in Oncology: collaborator
• Novartis: collaborator

Study Sites (1)

Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Edward Garon

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

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: February 5, 2013
• First Posted: February 6, 2013
• Study Start: January 31, 2014
• Primary Completion: October 11, 2018
• Study Completion: October 11, 2018
• Last Updated: September 3, 2020

Record last verified: 2018-04

Locations

US (1)