Phase 1 Safety and Tolerability Study of Andes-1537 for Injection in Patients With Advanced Unresectable Solid Tumors

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

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Unresectable Solid Tumors
• Intervention / Treatment: Drug: Andes-1537 for Injection

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF Medical Center at Mount Zion, Helen Diller Family Comprehensive Cancer Center, Early Phase Clinical Trials

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:

• 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
• Are unable or unwilling to follow protocol instructions and requirements

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: Andes-1537 for Injection; Part 1 is an open-label, dose-escalation study. Part 2 is an open-label, dose-expansion study.	Drug: Andes-1537 for Injection; Part 1: Andes-1537 subcutaneous injection, 100 to 1000 mg twice a week per 4-week cycle Part 2: Andes-1537 subcutaneous injection, recommended phase 2 dose administered twice a week per 4-week cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities	Determine maximum tolerated dose	First 4-week treatment cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Incidence of treatment-emergent adverse events	Safety evaluations will be measured through 28 days after last dose of Andes-1537
Safety laboratory tests	Changes in baseline safety laboratory tests	Safety evaluations will be measured through 28 days after last dose of Andes-1537
Physical examinations	Changes in baseline physical examination	Safety evaluations will be measured through 28 days after last dose of Andes-1537
Vital signs	Changes in baseline vital signs	Safety evaluations will be measured through 28 days after last dose of Andes-1537
12-lead electrocardiogram (ECG)	Changes in baseline ECG	First 4-week treatment cycle
Injection site reactions	Incidence of 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	Measure maximum concentration, time to maximum concentration, area under the curve, clearance, volume of distribution, and half-life	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	Evaluate biomarkers in tissue and blood	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	Changes in tumor size from baseline measurements	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

Collaborators and Investigators

• Sponsor: Andes Biotechnologies
• Investigators: Principal Investigator: Pamela Munster, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2015
• Primary Completion (Actual): November 13, 2017
• Study Completion (Actual): November 13, 2017

Study Registration Dates

• First Submitted: July 15, 2015
• First Submitted That Met QC Criteria: July 23, 2015
• First Posted (Estimate): July 27, 2015

Study Record Updates

• Last Update Posted (Actual): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 16, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Cancer; Neoplasms; Solid Tumors; Advanced Malignancy
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AB1537-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO