A Phase 1 Open-label First-in-human Dose-escalating Safety and Tolerability Study Evaluating Subcutaneous Administration of Andes-1537 for Injection in Patients With Advanced Unresectable Solid Tumors That Are Refractory to Standard Therapy or For Which No Standard Therapy is Available

Andes Biotechnologies1 site in 1 country22 target enrollmentDecember 8, 2015

ConditionsAdvanced Unresectable Solid Tumors

InterventionsAndes-1537 for Injection

DrugsAndes-1537 for Injection

Overview

Phase: Phase 1
Intervention: Andes-1537 for Injection
Conditions: Advanced Unresectable Solid Tumors
Sponsor: Andes Biotechnologies
Enrollment: 22
Locations: 1
Primary Endpoint: Incidence of dose-limiting toxicities
Status: Terminated
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a first-in-human, open-label, dose escalation and expansion, 2-part study to determine the safety, tolerability, and maximum tolerated dose of Andes-1537 for Injection in patients with advanced unresectable solid tumors that are refractory to standard therapy or for which no standard therapy is available.

Detailed Description

Part 1 is a dose-escalation study to establish the maximum tolerated dose based on dose-limiting toxicities and to evaluate the safety and tolerability of multiple doses of Andes-1537 for Injection in patients with advanced unresectable solid tumors that are refractory to standard therapy or for which no standard therapy is available. Part 2 is an open-label, dose-expansion study to determine the safety, tolerability, and preliminary efficacy of Andes-1537 in patients with advanced solid tumors. In part 2, patients will be enrolled and receive the recommended phase 2 dose established in part 1 based on the safety, tolerability, pharmacokinetics, and preliminary efficacy data.

Registry

clinicaltrials.gov

Start Date

December 8, 2015

End Date

November 13, 2017

Last Updated

7 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Andes Biotechnologies

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Men and women 18 years of age or older
•Can understand and voluntarily sign an informed consent form prior to any study-related assessments or procedures, and are able to adhere to the study visit schedule and other protocol requirements
•Patient with documented pathological evidence of a cancer from which has developed advanced unresectable solid tumors that are, in the opinion of their treating physician, refractory to standard therapy or for which no standard therapy is available
•Consent to tumor biopsy from accessible tissue (optional in Part 1 and mandatory in Part 2)
•Have measureable disease by RECIST
•Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
•Have adequate organ function, confirmed by the following laboratory values obtained ≤ 3 days prior to the first treatment: absolute neutrophil count ≥ 1.5 × 10\^9/L; hemoglobin ≥ 9 g/dL; platelets ≥ 100 × 10\^9/L; aspartate transaminase and alanine transaminase ≤ 2.5 × upper limit of normal (ULN); serum total bilirubin ≤ 2.0 × ULN; serum creatinine ≤ 1.5 × ULN, or estimated or measured creatinine clearance ≥ 60 mL/min; prothrombin time, activated partial thromboplastin time ≤ 1.5 × ULN if not on anticoagulation therapy
•Female patients of childbearing potential must have a negative serum pregnancy test and be using adequate contraception prior to study entry and must agree to use adequate contraception from study entry through at least 6 months after discontinuation of study drug.
•Male patients at screening must agree to practice adequate contraception from study entry through at least 6 months after discontinuation of study drug.

Exclusion Criteria

•Have symptomatic central nervous system metastases. Patients with brain metastases that have been previously treated and are stable for ≥ 4 weeks or treated with gamma knife surgery and are stable for ≥ 2 weeks are allowed to enter the study.
•Have unstable angina, clinically significant cardiac arrhythmia, New York Heart Association Class 3 or 4 congestive heart failure, or prolonged QT interval corrected wave of greater than 470 ms.
•Receiving treatment with any medication known to produce QT prolongation within 7 days of study entry
•Have had prior systemic chemotherapy treatments or investigational modalities ≤ 5 half-lives or 4 weeks, whichever is shorter, prior to starting treatment with Andes-1537 or who have not recovered from side effects, grade 2 or greater, of such therapy (except alopecia)
•Have had major surgery ≤ 2 weeks prior to starting treatment with Andes-1537 or who have not recovered from side effects of such surgery
•Are pregnant or breastfeeding
•Have had DVT or venous thromboembolism within 6 weeks of study entry
•Have active uncontrolled bleeding or a known bleeding disorder
•Have any serious or unstable concomitant systemic conditions that are incompatible with this clinical study, including but not limited to substance abuse, psychiatric disturbance, or uncontrolled intercurrent illness (including active infection), arterial thrombosis, or symptomatic pulmonary embolism
•Have a known sensitivity to any of the components of Andes-1537

Arms & Interventions

Andes-1537 for Injection

Part 1 is an open-label, dose-escalation study. Part 2 is an open-label, dose-expansion study.

Intervention: Andes-1537 for Injection

Outcomes

Primary Outcomes

Incidence of dose-limiting toxicities

Time Frame: First 4-week treatment cycle

Determine maximum tolerated dose

Secondary Outcomes

Adverse events(Safety evaluations will be measured through 28 days after last dose of Andes-1537)
Physical examinations(Safety evaluations will be measured through 28 days after last dose of Andes-1537)
Vital signs(Safety evaluations will be measured through 28 days after last dose of Andes-1537)
12-lead electrocardiogram (ECG)(First 4-week treatment cycle)
Injection site reactions(Safety evaluations will be measured through 28 days after last dose of Andes-1537)
Pharmacokinetic parameters in Andes-1537 in blood and urine for single-dose and multiple-dose evaluation(Pre-treatment, following first dose and last dose of cycle 1 (4-week cycle), first dose of each additional cycle through study completion, and last visit)
Pharmacodynamic parameters in blood and biopsy samples from accessible tissue(Pre-treatment and at 4 and 8 weeks for biopsy; blood samples at pre-treatment, every 8 weeks, and last visit)
Objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) with CT or MRI scan(Every 8 weeks following completion of 2 treatment cycles to cover from date of initiation until date of first documented progression or toxicity to Andes-1537, which ever comes first)
Safety laboratory tests(Safety evaluations will be measured through 28 days after last dose of Andes-1537)