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About
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
Full description
PRIMARY OBJECTIVES:
I. Evaluate the safety and tolerability of escalating doses of AUY922 (Hsp90 inhibitor AUY922) when given with pemetrexed (pemetrexed disodium) 500 mg/m^2 in participants with previously-treated stage IV non-squamous, non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. Determine the objective tumor response rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in participants with previously treated non-squamous NSCLC treated with pemetrexed and AUY922.
II. Evaluate the pharmacokinetic profile of pemetrexed and AUY922. III. Evaluate toxicity, including visual toxicity, in participants treated with AUY922 and pemetrexed.
IV. Analyze tumor-tissue biomarkers for potential correlation with response.
OUTLINE: This is a dose-escalation study of Hsp90 inhibitor AUY922.
Patients receive Hsp90 inhibitor AUY922 intravenously (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.
After completion of study treatment, patients are followed up at 30 days.
Enrollment
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Inclusion criteria
Exclusion criteria
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:
Participants with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome)
Intolerance of Vitamin B12, folic acid or dexamethasone
Participants with following cardiac criteria:
Participants unwilling or unable to comply with the protocol
Participants known to be human immunodeficiency virus (HIV) positive; testing is not required in the absence of clinical signs and symptoms suggesting HIV infection
Any systemic anti-cancer treatment out of allowed timelines
Concurrent cytotoxic or immunosuppressive therapy for non-malignant disease (e.g., for rheumatoid arthritis or lupus)
Primary purpose
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13 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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