Advanced Cancer Clinical Trial
Official title:
A Phase I, Multi-Center, Dose-Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of AV-412 Administered Orally Three Times Weekly to Subjects With Advanced Solid Tumors
Verified date | September 2011 |
Source | AVEO Pharmaceuticals, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | United States: Food and Drug Administration |
Study type | Interventional |
The Epidermal Growth Factor Receptor (EGFR) is a validated target for the treatment of
cancer, and agents targeting EGFR such as erlotinib (Tarceva®) are approved by the FDA for
treatment of various solid tumors. AV-412 is a novel inhibitor of the EGFR-tyrosine kinase,
with added activity against Her2 and other oncogenic kinases. Based on evidence of
preclinical activity in various solid tumors, AV-412 is being developed as a possible novel
treatment for cancer in humans.
PURPOSE: The purpose of this study is to test the safety and tolerability of AV-412, and
determine the maximum tolerated dose of AV-412 when administered orally three times weekly.
Status | Completed |
Enrollment | 37 |
Est. completion date | May 2010 |
Est. primary completion date | October 2009 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: 1. Ability to give written informed consent 2. 18 years and older 3. Evaluable disease or measurable disease according to RECIST. 4. Subjects enrolled in the MTD Cohort B must have the following: - A diagnosis of non-small cell lung carcinoma (NSCLC) - Received prior therapy with erlotinib or gefitinib for a minimum of 12 weeks - Demonstrated disease stabilization or an objective response during that prior treatment - Evidence of disease progression and measurable disease, according to RECIST 5. Histologically confirmed solid tumor malignancy that is locally advanced or metastatic 6. Disease that is currently refractory to, or not amenable to, standard therapy and/or subjects who are unwilling to try standard chemotherapy 7. Disease that is currently not amenable to surgical intervention, due to either medical contraindications or non-resectability of the tumor 8. Karnofsky performance status = 70% 9. Life expectancy = 3 months, as judged by the investigator 10. No childbearing potential; or use of a medically acceptable form of contraception during the study through the end of follow-up period Exclusion Criteria: 1. Pregnant or lactating women 2. Primary CNS malignancy and/or active CNS metastases (or leptomeningeal disease) not controlled by prior surgery or radiotherapy 3. Hematologic malignancies (including leukemia of any form, lymphoma, and multiple myeloma) 4. Active second malignancy or history of another malignancy within 2 years with the exception of: - Treated, non-melanoma skin cancers - Treated carcinoma in situ (CIS) of the breast or cervix - Controlled, superficial carcinoma of the bladder - T1a or b prostate carcinoma comprising < 5% of resected tissue, with prostate specific antigen (PSA) within normal limits (WNL) since resection 5. Any of the following hematologic abnormalities: - Hemoglobin = 9.0 g/dL - ANC = 1500 per mm3 - Platelet count = 75,000 per mm3 6. Any of the following serum chemistry abnormalities: - Total bilirubin > 1.5 × the ULN - AST or ALT = 3 × ULN (= 5 × ULN if due to hepatic involvement by tumor) - Serum albumin < 2.5 g/dL - Creatinine = 1.5 × ULN 7. Significant cardiovascular disease or condition, including: - Congestive heart failure requiring therapy - Ventricular arrhythmia requiring therapy - Severe conduction disturbance (including QTc interval prolongation > 0.47 sec [corrected], history of a severe arrhythmia, or history of a familial arrhythmia [eg, Wolff-Parkinson-White syndrome]) - Angina pectoris requiring therapy - Left ventricular ejection fraction (LVEF) < 50% by MUGA or echocardiogram - Uncontrolled hypertension (as determined by investigator) - Myocardial infarction (MI) within 6 months prior to administration of first dose - >Class I cardiovascular disease according to the New York Heart Association's (NYHA) Functional Criteria 8. Significant gastrointestinal abnormalities, including: - Requirement for IV alimentation - Prior surgical procedures affecting absorption - Active peptic ulcer disease - Grade 2 diarrhea due to any etiology - Ulcerative colitis or Crohn's disease 9. Known history of significant ophthalmologic abnormalities, including: - Severe dry eye syndrome - Keratoconjunctivitis sicca - Sjogren's syndrome - Severe exposure keratopathy - Disorders that might increase the risk for epithelium-related complications (eg, bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis) 10. Serious/active infection or any infection requiring parenteral antibiotics 11. Inadequate recovery from prior antineoplastic therapy 12. Inadequate recovery from any prior surgical procedure or major surgical procedure within 2 weeks prior to administration of first dose 13. Life-threatening illness, or organ system dysfunction which, in the opinion of the investigator, would limit life expectancy to < 3 months, compromise the subject's safety, or interfere with evaluation of the safety of the study drug 14. Psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study procedures 15. Inability to comply with the protocol requirements Drugs and Treatments to be Excluded: 1. Any prior therapy with the following: - Doxorubicin at a cumulative dose > 450 mg/m2 or equivalent dose of another anthracycline (eg, daunorubicin, epirubicin, idarubicin) or anthracenedione (eg, mitoxantrone). - HKI-272 or any other irreversible EGFR tyrosine kinase inhibitor (eg, CI- 1033 and similar agents). 2. Therapy within 2 weeks prior to administration of the first dose or at any time during the study with: • Herbal preparations/supplements (except for a daily multivitamin/mineral supplement not containing herbal components) 3. Therapy within 3 weeks prior to administration of the first dose or at any time during the study with: - Erlotinib (Tarceva®) or gefitinib (Iressa®) - Antibodies to EGFR (eg, cetuximab, panitumumab) - Agents targeting HER2 (ErbB2) (eg, trastuzumab, lapatinib) 4. Therapy within 4 weeks prior to administration of the first dose or at any time during the study with: - Chemotherapy with the exception of the following: - Mitomycin C or nitrosoureas within 6 weeks prior to administration of first dose - High-dose chemotherapy with stem cell support within 6 months prior to administration of first dose - Other antineoplastic agents (standard or therapeutic) for primary malignancy, including but not limited to signal transduction inhibitors and monoclonal antibodies. - Immunotherapy, cancer vaccines, biological response modifiers 5. Systemic hormonal therapy within 4 weeks prior to administration of the first dose or at any time during the study, with the exception of the following allowed therapies: - Hormonal therapy for appetite stimulation or contraception - Nasal, ophthalmic, and topical glucocorticoid preparations - Oral replacement therapy for adrenal insufficiency - Stable hormonal therapy for prostate carcinoma - Low-dose maintenance, or short course (ie, 7 days) steroid therapy for other conditions 6. Any experimental therapy within 4 weeks prior to or at any time during the study 7. Radiotherapy for the primary malignancy: - Within 2 weeks prior to first study drug administration if involving =25% of marrow-containing bone - Within 4 weeks prior to first study drug administration if involving >25% of marrow-containing bone |
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
United States | Kansas Masonic Cancer Research Center | Kansas City | Kansas |
United States | Montefiore Medical Center | New York City | New York |
United States | Georgetown University Hospital | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
AVEO Pharmaceuticals, Inc. |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Evaluate the safety, tolerability, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of AV-412 administered orally 3 times weekly and once weekly in subjects with relapsed or refractory solid tumor malignancies. | 4 weeks (1 cycle) | Yes | |
Secondary | Characterize the pharmacokinetic (PK) profile of AV-412 | 8 weeks ( 2 cycles) | No | |
Secondary | Determine the effect of AV-412 on global and targeted gene expression patterns in blood from all subjects enrolled in the MTD expansion cohorts | 8 weeks (2 cycles) | No | |
Secondary | Evaluate the antineoplastic activity of AV-412 | 8 weeks (2 cycles) | No |
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