Study of Safety and Tolerability of VLX600, an Iron Chelator, in Patients With Refractory Advanced Solid Tumors

A Phase I Study of the Safety and Tolerability of VLX600, an Iron Chelator, in Patients With Refractory Advanced Solid Tumors

The purpose of this study is to evaluate the safety and tolerability of the investigational drug VLX600 in patients with refractory advanced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Refractory Cancer
• Intervention / Treatment: Drug: VLX600

Detailed Description

This Phase I, open label dose escalation study of VLX600 in patients with refractory advanced solid tumors will determine the safety profile and maximum tolerated dose (MTD) of VLX600 when administered by intravenous infusion on Days 1, 8, and 15 of each 28-day treatment cycle. Dose escalation will proceed according to the standard "3 + 3" design using doubling doses. The doses are: 10, 20, 40, 80, 160, and 210 mg VLX600.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester

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:

1. Men and women greater than or equal to 18 years of age.
2. Histologic evidence of advanced solid tumors (excluding central nervous system (CNS) primary tumors) non-resectable, refractory to standard therapies, or patient cannot receive or refuses standard therapy.
3. Solid tumors measurable according to RECIST 1.1 or solid tumors not measurable according to RECIST 1.1, but which express tumor markers (e.g., prostate cancer with prostate specific antigen (PSA) expression or ovarian cancer with cancer antigen-125 (CA-125) expression) are eligible.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

5. Must have the following laboratory values, obtained less than or equal to 7 days prior to registration:

   • Absolute neutrophil count (ANC) greater than or equal to 1500/µL
   • Platelet (PLT) count greater than or equal to 100,000/µL
   • Total bilirubin less than 1.5 x upper normal limit (UNL)
   • Aspartate aminotransferase (AST) (SGOT) less than or equal to 3 x UNL
   • Creatinine less than 1.5 x UNL
6. Women of childbearing potential must have a negative serum pregnancy test less than or equal to 7 days prior to registration.
7. Life expectancy greater than 12 weeks.
8. Must provide written informed consent.
9. Must be willing to return to Mayo Clinic enrolling institution for follow-up.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes mellitus, seizure disorder or psychiatric illness/social situations that would limit compliance with study requirements.

2. Treatment with any of the following prior therapies:

   • Chemotherapy less than or equal to 4 weeks prior to registration
   • Mitomycin C/nitrosoureas less than or equal to 6 weeks prior to registration
   • Immunotherapy less than or equal to 4 weeks prior to registration
   • Biologic therapy less than or equal to 4 weeks prior to registration
   • Radiation therapy less than or equal to 4 weeks prior to registration
   • Non-cytotoxic therapy less than or equal to 5 half-lives prior to registration
3. Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment.
4. Major surgery less than 28 days prior to study entry.
5. Active other malignancy, except non-melanoma skin cancer or carcinoma-in-situ (e.g., of cervix, breast, prostate). If there is a history of prior malignancy, patient must not be receiving other specific treatment (other than hormonal therapy) for the cancer.
6. CNS metastases if not previously treated and stable for at least 2 months per imaging and clinical assessment.

7. Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

   • Pregnant women
   • Nursing women
   • Men or women of childbearing potential unwilling to employ adequate contraception
8. Other concurrent chemotherapy, immunotherapy, radiotherapy, any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation) or receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
9. Cardiac issues consisting of either symptomatic congestive heart failure (NYHA Class II or higher), unstable angina pectoris, myocardial infarction within 6 months, and/or cardiac arrhythmia, including atrial fibrillation (which is symptomatic or requires treatment).
10. Corrected QT interval (QTc) interval greater than 450 msec (males) or greater than 470 msec (females).
11. Immunocompromised patients (other than that related to the use of corticosteroids) including patients with a known history of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
12. Clinically relevant retinal abnormalities as per the medical history or ophthalmologic findings in the pretreatment evaluation (e.g., retinitis pigmentosa or macular degeneration).
13. History of thromboembolism within the past 5 years, history of catheter-related thrombophlebitis or other clinically significant thrombophlebitis are excluded.

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: VLX600; Dose of VLX600 in patients with refractory advanced solid tumors

Drug: VLX600; Patients will receive a dose of VLX600 by 4-hr intravenous infusion using a central venous catheter on Days 1, 8, and 15 of each 28-day treatment cycle. There are the following dose cohorts: 10, 20, 40, 80, 160, and 210 mg VLX600. It is anticipated that patients will receive 6 treatment cycles. In the absence of unacceptable toxicity and disease progression, patients have the option of continuing treatment beyond 6 cycles, if the investigator determines that the patient may benefit further from it.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessment of adverse event (AE) profile	AEs are assessed from first treatment day through at least 30 days after last treatment.
Determination of the maximum tolerated dose (MTD) of VLX600	MTD will be determined during dose escalation phase of study, up to one year.
Determination of the recommended Phase II dose (RPTD) of VLX600	Determination of RPTD will be based on adverse event profile, up to one year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of the tumor response to VLX600 treatment	Tumor response will be determined using CT scans or magnetic resonance imaging (MRI) at pre-treatment, Cycle 2 Day 28, at every 8 weeks thereafter, and at off-study (if a scan has not been performed within the last prior 4 weeks). Patients in the MTD confirmation cohort only will have a pre-treatment baseline positron emission tomography- computerized tomography (PET-CT) scan and then at Cycle 2 Day 28. Tumor response will be determined by Response Criteria in Solid Tumors (RECIST) version 1.1. In patients with disease not measurable by RECIST 1.1, blood samples for biomarkers of tumor response will be collected at pre-treatment baseline and then after every 8 weeks.	Tumor response will be evaluated by CT scans or MRI at pre-treatment baseline and on Cycle 2 Day 28, then after every 8 weeks, and then at off-study (if greater than 4 weeks since prior tumor assessment).
Description of progression-free survival		Progression-free survival is calculated from date of first treatment until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 200 days (through 6 treatment cycles).
Description of the pharmacokinetics (PK) of VLX600	Blood samples will be collected for PK analysis at the specified time points in Cycle 1 only.	PK assessed in Cycle 1 only. Day 1: pre-dose, 15, 30, 60 min, and 2, 4, 4.25, 4.5, 5, 8 hrs post start of infusion. Day 2: 24 hr post-start of infusion. Day 8: pre-dose, Day 15 (same as Day 1), Day 16: 24 hr post-start of infusion, and Day 22: pre-dose
Description of overall survival.		Overall survival will be determined from date of first study treatment until death due to any cause, up to 72 weeks (duration of study).

Collaborators and Investigators

• Sponsor: Vivolux AB
• Collaborators: Theradex
• Investigators: Study Chair: Elizabeth Johnson, MD, Mayo Clinic; Principal Investigator: Aaron Mansfield, MD, Mayo Clinic, Rochester, MN; Principal Investigator: Mitesh J Borad, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2015
• Primary Completion (Actual): December 28, 2016
• Study Completion (Actual): December 28, 2016

Study Registration Dates

• First Submitted: August 15, 2014
• First Submitted That Met QC Criteria: August 20, 2014
• First Posted (Estimate): August 21, 2014

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Phase I; Safety and tolerability; Iron chelator; Refractory advanced solid tumors; Dose escalation study; Tumor response by RECIST 1.1; Progression-free survival; Overall survival Pharmacokinetics
• Other Study ID Numbers: V13-11045; IND 118039 (Other Identifier: CDER/DOP2/OHOP)