NCT01147029TerminatedPhase 1
A Cancer Research UK Phase I Trial of 4-(N-(S-Glutathionylacetyl) Amino) Phenylarsenoxide (GSAO) Given as Daily Intravenous Infusions on Days 1-5 and 8-12 of a 21-Day Cycle, to Patients With Advanced Solid Tumors
Conditions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Cancer Research UK
- Enrollment
- 35
- Locations
- 4
- Primary Endpoint
- Dose-limiting toxicity
Study Overview
Brief Summary
RATIONALE: GSAO may stop the growth of solid tumors by blocking blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of GSAO in treating patients with advanced solid tumors that have not responded to therapy.
Detailed Description
OBJECTIVES:
Primary
- To determine the maximum-tolerated dose and recommended phase II dose of angiogenesis inhibitor GSAO in patients with advanced, refractory solid tumors.
- To assess the safety and toxicity profile and dose-limiting toxicity of this drug in these patients.
Secondary
- To determine the pharmacokinetics of this drug in these patients.
- To determine the pharmacodynamics of this drug in these patients.
- To determine possible anti-tumor activity in patients treatment with this drug.
Study Design
- Study Type
- Interventional
- Primary Purpose
- Treatment
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed advanced solid tumor
- •Refractory to conventional treatment or for which no conventional therapy exists
- •Disease assessable by DCE-MRI and should be of a size that can be adequately assessed by these techniques
- •No known primary brain tumors or brain metastases
- •PATIENT CHARACTERISTICS:
- •WHO performance status 0-1
- •Life expectancy ≥ 12 weeks
- •Hemoglobin ≥ 9.0 g/dL
- •Platelet count ≥ 100 x 10^9/L
- •Neutrophil count ≥ 1.5 x 10^9/L
- •Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT and AST ≤ 2.5 times ULN
- •Creatinine clearance ≥ 50 mL/min (uncorrected value)
- •Serum potassium and magnesium normal
- •No proteinuria > grade 1 either on 24-hour urine or on 2 consecutive dipsticks taken no less than 1 week apart
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception 4 weeks prior to, during, and for 6 months after completion of study therapy
- •Not at high medical risk due to non-malignant systemic disease, including active uncontrolled infection
- •No serologically positive hepatitis B, hepatitis C, or HIV
- •No concurrent congestive heart failure or prior NYHA class III-IV cardiac disease
- •None of the following medical conditions:
- •Angina (stable or severe, even if well controlled on medication)
- •Myocardial infarction in the past 2 months by ECG
- •Congestive cardiac failure
- •Arrhythmias, including any condition associated with QTc prolongation (e.g., Lange-Neilson syndrome or Romano Ward syndrome)
- •Evidence of ischemia
- •QTc > 480 msec
- •Other clinically significant abnormalities
- •No uncontrolled hypertension (defined as BP consistently greater than 160/100 mm Hg irrespective of medication)
- •No other condition that, in the opinion of the investigator, would not make the patient a good candidate for this clinical trial
- •No pacemakers
- •No metal fragments in the eyes or shrapnel or bullet injuries
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •Recovered from all prior treatments (except for alopecia or certain grade 1 toxicities which, in the opinion of the investigator and Cancer Research UK, should not exclude the patient)
- •At least 4 weeks since prior radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, or chemotherapy (6 weeks for nitrosoureas and mitomycin C)
- •At least 1 week since prior and no concurrent shellfish
- •At least 6 weeks since prior major surgery (including thoracic and/or abdominal surgery) and recovered
- •Concurrent luteinizing-hormone releasing-hormone (LHRH) analogues allowed for patients with castration-refractory prostate cancer provided the prostate-specific antigen level is rising
- •No prior heart or brain surgery
- •No concurrent drug known to prolong the QTc interval
- •No concurrent warfarin (1 mg for maintenance of a Hickman line is acceptable) or heparin (flushing of arterial lines, if necessary, is acceptable)
- •No concurrent naproxen (other NSAIDs are acceptable)
- •No concurrent prophylactic use of antiemetics during the first treatment
- •Domperidone and lorazepam must not be used as antiemetics
- •No other concurrent anticancer therapy or investigational drugs
- •Concurrent bisphosphonates allowed
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Dose-limiting toxicity
Causality of each adverse event and grading severity according to NCI CTCAE Version 3.0
Secondary Outcomes
- Relationship between pharmacokinetics and toxicity and/or markers of efficacy
- Changes in microvascular function using DCE-MRI
- Plasma and tumor levels of angiogenic factors and apoptosis markers
- Response (stable disease, partial response, or complete response) as determined by RECIST criteria
- Circulating endothelial cells and circulating endothelial progenitor cells as a marker of inhibition of angiogenesis
Investigators
Study Sites (4)
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