GSAO in Treating Patients With Advanced Solid Tumors That Have Not Responded to Therapy

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01147029
• Other study ID #: CDR0000675271
• Secondary ID: CRUK-PH1-109EUDR
• Status: Terminated
• Phase: Phase 1
• First received: June 17, 2010
• Last updated: April 30, 2012
• Start date: January 2008
• Est. completion date: April 2012

Study information

• Verified date: April 2012
• Source: Cancer Research UK
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Tertiary

• To further determine the pharmacodynamics of this drug in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive angiogenesis inhibitor GSAO IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients showing clinical benefit (i.e., stable disease, partial response, or complete response) may receive 6 additional courses of treatment. Patients receive angiogenesis inhibitor GSAO IV over 1 hour on day -7 to obtain pharmacokinetics information of a single IV dose of the drug.

Patients also undergo dynamic contrast-enhanced magnetic-resonance imaging (DCE-MRI) prior to, during, and after study to determine blood flow parameters.

Blood samples are collected periodically for pharmacokinetic, pharmacodynamic, and biomarker studies.

After completion of study treatment, patients are followed up for 28 days and then once a month thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• angiogenesis inhibitor GSAO

Other:
• laboratory biomarker analysis

• pharmacological study

Procedure:
• dynamic contrast-enhanced magnetic resonance imaging

Locations

Country	Name	City	State
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Churchill Hospital	Oxford	England

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity			Yes
Primary	Causality of each adverse event and grading severity according to NCI CTCAE Version 3.0			Yes
Secondary	Relationship between pharmacokinetics and toxicity and/or markers of efficacy			Yes
Secondary	Changes in microvascular function using DCE-MRI			No
Secondary	Plasma and tumor levels of angiogenic factors and apoptosis markers			No
Secondary	Response (stable disease, partial response, or complete response) as determined by RECIST criteria			No
Secondary	Circulating endothelial cells and circulating endothelial progenitor cells as a marker of inhibition of angiogenesis			No