Safety and Pharmacokinetic Profiles of Two Formulations of CO-1.01 in Patients With Advanced Solid Tumors

NCT01392976 | Completed Phase 1

• 1 other identifier: CO-101-004
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to compare the pharmacokinetic and safety profiles of two formulations of CO-1.01 in patients with Advanced Solid Tumors.

Conditions

Advanced Solid Tumor

Keywords

cancer; advanced; solid; tumor; gemcitabine; human equilibrative nucleoside transporter-1 (hENT1); CO-1.01; CO-101; CO101

Outcome Measures

Primary Outcomes (1)

• Ratio of the AUC0-∞ of the two formulations of CO-1.01 given as a 30 min i.v. infusion at 1250 mg/m2

  Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8

Secondary Outcomes (4)

• PK of CO-1.01 and metabolites in plasma and urine after 1250 mg/m2 CO-1.01 given as a single 30 min i.v. infusion

  Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8

• QT/QTc interval of the ECG

  Continuous ECG monitoring 8 hrs pre & post dose C1: D1, D8. 12 lead ECGs pre-dose, 30mins, 24hr, 48hr, 72hr C1: D1, D8

• Relationship between plasma concentration of CO-1.01 and QT/QTc interval of the ECG

  Plasma: multiple timepoints through C1D1 and D8. ECG: continuous monitoring 8 hrs pre & post dose C1: D1, D8. 12 lead ECGs pre-dose, 30mins, 24hr, 48hr, 72hr C1:D1, D8.

• Drug tolerability and toxicity using clinical AE monitoring and clinical laboratory testing

  From the time of signing the ICF until 28 days after last dose of CO-101. CO-101 dosed on C1D1, C1D8, C1D15, C2D1, C2D8, and C2D15.

Study Arms (2)

CO-1.01 Formulation B

EXPERIMENTAL

Drug: CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids)

CO-1.01 Formulation A

ACTIVE COMPARATOR

Drug: CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids)

Interventions

CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids) DRUG

1250 mg/m2 intravenous infusion on Day 1 for Treatment Sequence 1 and Day 8 for Treatment Sequence 2.

CO-1.01 Formulation A

CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids) DRUG

1250 mg/m2 intravenous infusion on Day 1 for Treatment Sequence 2 and Day 8 for Treatment Sequence 1.

CO-1.01 Formulation B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis with a histologically confirmed solid tumor malignancy that is metastatic or unresectable for which there is no standard curative or palliative treatment option available and for which CO-1.01 treatment would be appropriate
• Life expectancy of at least 3 months
• Performance status (ECOG)0 or 1
• Age ≥18 years
• Adequate hematological and biological function
• Written consent on an Institutional Review Board/Independent Ethics Committee-approved IC Form prior to any study-specific evaluation

You may not qualify if:

• Clinically significant abnormal 12-lead ECG or QTcF\>450msec (males) or \>470 msec (females), PR\>240 msec, or a QRS\>110msec
• Family history of long QT syndrome
• Implantable pacemaker or implantable cardioverter defibrillator
• Symptomatic brain metastases
• Concomitant treatment with prohibited medications
• Treatment with a previous regimen of CO-1.01 within 30 days or randomization
• Treatment with any medication known to produce QT prolongation
• Surgical procedures are not allowed ≥14 days prior to administration of CO-1.01. In all cases, the patient must be sufficiently recovered and stable
• History of allergy to gemcitabine or eggs
• Females who are pregnant or breastfeeding
• Refusal to use adequate contraception for fertile patients (females and males) for 6 months after the last dose of CO-1.01
• Presence of any serious of unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, psychiatric disturbance, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism)
• Any other reason the investigator considers the patient should not participate in the study

Sponsors & Collaborators

• Clovis Oncology, Inc.: lead

Study Sites (3)

The Netherlands Cancer Institute

Amsterdam, 1066 CX, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Jan Schellens, MD PhD

  The Netherlands Cancer Institute, Amsterdam, Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2011
• First Posted: July 13, 2011
• Study Start: April 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: April 1, 2013
• Last Updated: August 15, 2014

Record last verified: 2014-08

Locations

NL (3)