Phase 2 Study to Investigate the Efficacy and Safety of Aldoxorubicin in Subjects With Glioblastoma

An Open-Label Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of Aldoxorubicin in Subjects With Unresectable Glioblastoma Whose Tumors Have Progressed Following Prior Treatment With Surgery, Radiation and Temozolomide

This is a pilot study to determine the efficacy and safety of aldoxorubicin in subjects with glioblastoma who have progressed following surgery and prior treatments.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: 250 mg/m2 aldoxorubicin; Drug: 350 mg/m2 aldoxorubicin

Detailed Description

This is a second line open-labeled pilot phase 2 study in subjects with glioblastoma whose tumors have progressed following prior treatment with surgery, radiation and Temozolomide. Patients who have received avastin as a second-line treatment are not eligible for this study.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70115-6969
      • Ochsner Health System
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology-Austin Midtown

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or older; male or female
2. Histologically or cytologically confirmed unresectable GBM. Subjects with recurrent disease whose prior pathology demonstrated GBM will not need to be re-biopsied. Subjects with prior low-grade glioma or anaplastic glioma are eligible if histological assessment demonstrates transformation into GBM.

3. Cancer progression after treatment with the following: surgery, radiation therapy and temozolomide as first line treatment with no other therapy prior to tumor recurrence.

   1. Radiographic progression by RANO Working Group Criteria will be confirmed by Imaging Endpoints, a central imaging vendor.
   2. By tumor biopsy if conducted within 4 weeks of randomization.
4. An interval of at least 12 weeks after last dose of radiation and temozolomide is required, unless cancer progression is proven by diagnostic tumor biopsy. If temozolomide is being used in a maintenance phase, there must be a 28-day washout period prior to Randomization.
5. Stable or decreasing dose of corticosteroids for at least 7 days prior to randomization.
6. Capable of providing informed consent and complying with trial procedures.
7. Karnofsky Performance Status 70 or above.
8. ECOG performance status 0-2.
9. Life expectancy 8 or more weeks.

10. Measurable tumor lesions according to RANO working Group Criteria.

    a. In the case that there is "non-measurable" disease due to a radical surgical resection during screening, the subject still qualifies if Inclusion #3(b) is met.

11. Women must not be able to become pregnant for the duration of the study.
12. Women of childbearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
13. Geographically accessible to site, i.e. the ability to come to the study site for each scheduled appointment and evaluation.

Exclusion Criteria:

1. Prior exposure to the an anthracycline.
2. Any therapeutic regimen for treatment of recurrent tumor after first line treatment with surgery, radiation and temozolomide.
3. Prior treatment with bevacizumab or an experimental anti-angiogenic agent.
4. Palliative surgery and/or radiation treatment less than 4 weeks to randomization.
5. Exposure to any investigational agent within 30 days of Randomization.
6. 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 3 or more years.
7. Laboratory values: screening serum creatinine > 1.5xULN, ALT > 2.5xULN, total bilirubin > 1.5xULN, ANC < 1500/mm3, platelet concentrations < 100,000/mm3, absolute lymphocyte count < 1000/mm3, hematocrit level < 27% for females or < 30% for males, serum albumin ≤ 2.5 g/dL, PT/INR 1.5xULN or >3xULN on anticoagulant with no evidence of active bleeding.
8. Evidence of CNS hemorrhage CTCAE ≥ grade 2 on baseline MRI.
9. Clinically evident congestive heart failure > class II of the NYHA guidelines.
10. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrythmias classified as Lown III, IV or V.
11. History or signs of active coronary artery disease with or without angina pectoris.
12. Serious myocardial dysfunction defined as ultrasound-determined LVEF < 45% of predicted institutional normal value.
13. Baseline ATc>470 msec and/or previous history of QT prolongation.
14. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or anti-fungals.
15. History of HIV infection.
16. Major surgery, except diagnostic tumor biopsy, within 4 weeks of randomization.
17. Any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
18. 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: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 250 mg/m2 aldoxorubicin; Subjects received 250 mg/m2 aldoxorubicin IV.	Drug: 250 mg/m2 aldoxorubicin; Other Names: INNO-206
Experimental: 350 mg/m2 aldoxorubicin; Subjects received 350 mg/m2 aldoxorubicin IV.	Drug: 350 mg/m2 aldoxorubicin; Other Names: INNO-206

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (Complete Response and Partial Response)	ORR was defined as the proportion of patients with objective CR or PR by RANO working group criteria. CR: required all the following: complete disappearance of all enhancing measurable/ non-measurable disease sustained for at least 4 weeks; no new lesions; stable or improved non-enhancing (T2/FLAIR) lesions; patients must be off corticosteroids (or on physiologic replacement doses only); and stable or improved clinically. Patients with non-measurable disease only cannot have a CR. PR: Requires all of the following: ≥50% decrease compared with baseline sustained for at least 4 weeks; no PD of non-measurable disease; no new lesions; stable or improved non-enhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at the time of the baseline scan; and stable or improved clinically. Patients with non-measurable disease only can't have a PR.	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	The secondary objectives of this study are to evaluate the safety of aldoxorubicin in this population assessed by the frequency and severity of adverse events (AEs, abnormal findings on physical examination, laboratory tests, vital signs, echocardiogram evaluations, ECG results, weight, and the change in performance status as measured by the Karnofsky Performance Scale.	up to 6 months

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: December 9, 2013
• First Submitted That Met QC Criteria: December 12, 2013
• First Posted (Estimated): December 18, 2013

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: glioblastoma; brain tumor; brain cancer; temozolomide; aldoxorubicin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: ALDOXORUBICIN-P2-GBM-01