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

Advanced Unresectable Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02508441
• Other study ID #: AB1537-001
• Status: Terminated
• Phase: Phase 1
• Start date: December 8, 2015
• Est. completion date: November 13, 2017

Study information

• Verified date: October 2018
• Source: Andes Biotechnologies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: November 13, 2017
• Est. primary completion date: November 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Unresectable Solid Tumors

Intervention

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

Locations

Country	Name	City	State
United States	UCSF Medical Center at Mount Zion, Helen Diller Family Comprehensive Cancer Center, Early Phase Clinical Trials	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Andes Biotechnologies

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities	Determine maximum tolerated dose	First 4-week treatment cycle
Secondary	Adverse events	Incidence of treatment-emergent adverse events	Safety evaluations will be measured through 28 days after last dose of Andes-1537
Secondary	Safety laboratory tests	Changes in baseline safety laboratory tests	Safety evaluations will be measured through 28 days after last dose of Andes-1537
Secondary	Physical examinations	Changes in baseline physical examination	Safety evaluations will be measured through 28 days after last dose of Andes-1537
Secondary	Vital signs	Changes in baseline vital signs	Safety evaluations will be measured through 28 days after last dose of Andes-1537
Secondary	12-lead electrocardiogram (ECG)	Changes in baseline ECG	First 4-week treatment cycle
Secondary	Injection site reactions	Incidence of injection site reactions	Safety evaluations will be measured through 28 days after last dose of Andes-1537
Secondary	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
Secondary	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
Secondary	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