Study to Investigate the Safety and Activity of Aldoxorubicin Plus Gemcitabine in Subjects With Metastatic Solid Tumors

An Open-Label Phase 1b Study to Investigate the Preliminary Safety and Activity of Aldoxorubicin Plus Gemcitabine in Subjects With Metastatic Solid Tumors

This is a Phase 1 study to investigate the safety and activity of aldoxorubicin plus gemcitabine in Subjects with solid tumors.

Study Overview

• Status: Completed
• Conditions: Metastatic Solid Tumors
• Intervention / Treatment: Drug: gemcitabine; Drug: aldoxorubicin; Drug: aldoxorubicin; Drug: aldoxorubicin

Detailed Description

An open-label Phase 1b study to investigate the preliminary safety and activity of aldoxorubicin plus gemcitabine in subjects with metastatic solid tumors administered at doses of 170, 250 or 350 mg/m2 by intravenous infusion (IVI) on Day 1 every 21 days plus 900 mg/m2 gemcitabine on Days 1 and 8 every 21 days.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Virginia G. Piper Cancer Center
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 15-80 years, male or female.
2. Advanced, unresectable, metastatic solid tumor that has either relapsed or was refractory to treatment with at least 1 prior chemotherapy or immunotherapy regimen and for which no standard approved therapy exists.
3. Progressive disease (PD) < 6 months prior to enrollment.
4. Capable of providing informed consent and complying with trial procedures.
5. ECOG PS 0-2 (Appendix B).
6. Life expectancy >12 weeks.
7. Measurable tumor lesions according to RECIST 1.1 criteria.
8. Women must not be able to become pregnant (eg post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. (Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.)
9. Males and their female partner(s) of child-bearing potential must use 2 forms of effective contraception (see Inclusion 8 plus condom or vasectomy for males) from the last menstrual period of the female partner during the study treatment and for 6 months after the final dose of study treatment.
10. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
11. Geographic accessibility to the site that ensures the subject will be able to keep all study-related appointments.

Exclusion Criteria:

1. Prior exposure to >5 cycles or 375 mg/m2 of either doxorubicin or Doxil®.
2. Chemotherapy, palliative surgery and/or radiation treatment less than 30 days prior to enrollment.
3. Exposure to any investigational agent within 30 days of enrollment.
4. CNS metastases that are symptomatic.
5. History of other malignancies except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix unless documented free of cancer for ≥5 years.
6. Laboratory values: Screening serum creatinine >1.5×ULN, ALT >3×ULN, or >5×ULN if liver metastases are present, total bilirubin >3×ULN, ANC <1,500/mm3, platelet concentration <100,000/mm3, hematocrit level <25% for females or <27% for males, coagulation tests (PT, PTT, INR) >1.5×ULN, and albumin <2.0 g/dL.
7. Clinically evident CHF > class II of the NYHA guidelines (Appendix D).
8. Current serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V (Appendix F).
9. Baseline QTc >470 msec and/or previous history of QT prolongation while taking other medications. Concomitant use of medications associated with a high incidence of QT prolongation is not allowed (Appendix G).
10. History or signs of active coronary artery disease with or without angina pectoris.
11. Serious myocardial dysfunction defined scintigraphically (eg MUGA, myocardial scintigram) or ultrasound determined absolute LVEF <45% of predicted.
12. History of HIV infection.
13. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
14. Major surgery within 21 days prior to enrollment.
15. Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
16. Any condition that is unstable and could jeopardize the subject's participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: aldoxorubicin

Drug: gemcitabine; Drug: aldoxorubicin; administered at 170 mg/m2 by intravenous infusion (IVI) on Day 1 every 21 days plus 900 mg/m2 gemcitabine on Days 1 and 8 every 21 days.; Other Names: INNO-206; Drug: aldoxorubicin; administered at 250 mg/m2 by intravenous infusion (IVI) on Day 1 every 21 days plus 900 mg/m2 gemcitabine on Days 1 and 8 every 21 days.; Other Names: INNO-206; Drug: aldoxorubicin; administered at 350 mg/m2 by intravenous infusion (IVI) on Day 1 every 21 days plus 900 mg/m2 gemcitabine on Days 1 and 8 every 21 days.; Other Names: INNO-206

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Measures	The primary objective of this study is to determine the preliminary safety of administration of aldoxorubicin in combination with gemcitabine in subjects with metastatic solid tumors as measured by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, vital signs, echocardiograms (ECHO) or multiple-gated acquisition (MUGA) scans, electrocardiogram (ECG) results, and weight.	14 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response	The secondary objective of this study is to evaluate the activity of aldoxorubicin in combination with gemcitabine in this population, assessed by overall response rate (ORR) and progression-free survival (PFS).	17 months

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.
• Investigators: Study Director: Dan Levitt, M.D., CytRx Coporation

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: August 15, 2014
• First Submitted That Met QC Criteria: September 8, 2014
• First Posted (Estimate): September 10, 2014

Study Record Updates

• Last Update Posted (Actual): February 10, 2022
• Last Update Submitted That Met QC Criteria: January 27, 2022
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: phase 1; solid tumors; gemcitabine; INNO-206; aldoxorubicin
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Gemcitabine; Doxorubicin
• Other Study ID Numbers: ALDOXORUBICIN-P1-MTD-03