Study of Oral Darinaparsin in Patients With Advanced Solid Tumors

Phase I Study of Oral Darinaparsin in Advanced Solid Tumors

This study is a Phase I, dose escalation study of oral darinaparsin for the treatment of advanced solid tumors. Eligible patients could have received any amount of previous therapy.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: darinaparsin

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Lafayette, Indiana, United States, 47905
  • Texas
    • Dallas, Texas, United States
    • Houston, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with histological or cytological confirmation of advanced cancer (solid tumor) that is refractory to standard therapies for their condition;
• Men and women of ≥18 years of age;
• ECOG performance score ≤2
• Eligible subjects with solid tumors MUST have at least one measurable lesion as defined by RECIST 1.1 guidelines. If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology. Measurable lesions MUST NOT have been in a previously irradiated field or injected with biological agents;
• Life expectancy ≥12 weeks;

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements, to be conducted <2 weeks prior to Baseline:

  • Creatinine ≤1.5 × upper limit of normal (ULN) OR a calculated creatinine clearance ≥50 cc/min
  • Total bilirubin ≤2 × ULN
  • Alanine transaminase (ALT) and aspartate transaminase (AST)≤3 × ULN
  • Granulocytes in peripheral blood ≥1 × 109/L, hemoglobin ≥10 g/dL, and platelets ≥50,000 /µL
• Adequate vascular access for repeated blood sampling;
• Men and women of childbearing potential must agree to use effective contraception from Screening through the duration of Study participation;
• Written informed consent in compliance with ZIOPHARM policies and the Human Investigation Review Committee (IEC/IRB) having jurisdiction over the site.

Exclusion Criteria:

• Arsenic allergy.
• New York Heart Association (NYHA) functional class ≥3 myocardial infarction (see Appendix 3) within 6 months.
• Uncontrolled cardiac arrhythmia other than asymptomatic atrial fibrillation; a QTc ≥450 msec; or a ≥Grade 2 atrioventricular (AV) block or left bundle branch block (LBBB); or documented history of prolonged QTc.
• Pregnant and/or lactating women.
• Uncontrolled systemic infection (documented with microbiological studies).
• Metastatic brain or meningeal tumors.
• Patients with seizure disorder requiring medication (such as anti-epileptics)
• History of confusion or dementia or neurological condition that could mask a potential adverse response to the Study Drug, which may include transient ischemic attack, Parkinson's disease, thrombotic or hemorrhagic stroke, Alzheimer's, and other neurological disorders.
• Anticancer chemotherapy or immunotherapy during the study or within four weeks of Study entry (mitomycin C or nitrosureas should not be given within 6 weeks of Study entry)
• Radiotherapy during study or within 3 weeks of Study entry.
• Major surgery within 4 weeks of start of Study Drug dosing.
• Other Investigational drug therapy during this trial within four weeks prior to Study entry.
• History of invasive second primary malignancy diagnosed within the previous 3 years except for Stage I endometrial/cervical carcinoma or prostate carcinoma treated surgically, and non-melanoma skin cancer.
• Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of Study results.
• Any condition that is unstable or could jeopardize the safety of the patient and his/her compliance in the Study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral darinaparsin; open label, single arm, dose escalation	Drug: darinaparsin; dose escalating, starting at 200 mg twice per day for 21 days continuous followed by a 7 day rest per cycle.; Other Names: ZIO-101-C; S-dimethylarsino-glutathione; Zinapar (TM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine Toxicity Profile	a primary outcome measure is to determine the toxicity profile of oral darinaparsin when given continuously for 21 days followed by a 7 day rest period per cycle	One Year
Determine Maximum Tolerated Dose	a primary outcome measure is to determine the maximum tolerated dose of oral darinaparsin when given continuously for 21 days followed by a 7 day rest period per cycle	One Year
Determine the preliminary activity/efficacy	a primary outcome measure is to determine the preliminary activity/efficacy of oral darinaparsin when given continuously for 21 days followed by a 7 day rest period per cycle	One Year
Determine Pharmacokinetic profile	a primary outcome measure is to determine the pharmacokinetic profile of oral darinaparsin when given continuously for 21 days followed by a 7 day rest period per cycle	One Year

Collaborators and Investigators

• Sponsor: Alaunos Therapeutics

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: June 4, 2010
• First Submitted That Met QC Criteria: June 4, 2010
• First Posted (Estimate): June 8, 2010

Study Record Updates

• Last Update Posted (Estimate): July 19, 2012
• Last Update Submitted That Met QC Criteria: July 18, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: carcinoma; solid tumor; metastatic; sarcoma
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SGC1004