ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects With Glioblastoma Multiforme (GBM)

• ClinicalTrials.gov Identifier: NCT04587830
• Recruitment Status: Recruiting
• First Posted: October 14, 2020
• Last Update Posted: September 30, 2022
• Sponsor: Polaris Group
• Information provided by (Responsible Party): Polaris Group

Study Description

Brief Summary:

Assess safety and tolerability of ADI-PEG 20 in combination with radiotherapy and Temozolomide in newly diagnosed GBM

Condition or disease	Intervention/treatment	Phase
Glioblastoma Multiforme (GBM)	Drug: ADI-PEG20; Drug: Temozolomide	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1B Trial of ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects With Newly Diagnosed Glioblastoma Multiforme
• Actual Study Start Date: September 14, 2020
• Estimated Primary Completion Date: February 28, 2027
• Estimated Study Completion Date: May 30, 2027

Arms and Interventions

Arm

Intervention/treatment

Experimental: ADI-PEG 20 plus Radiotherapy and Temozolomide; ADI-PEG 20 Dose: 18 and 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Radiotherapy Dose: 60 Gy in 30 daily (Monday-Friday) fractions of 2 Gy each; to start within 5 weeks of surgery (diagnostic and/or resection) Temozolomide Dose: 75 mg/m2 daily during radiotherapy; 150-200 mg/m2 for 5 days every 4 weeks (1 cycle) x 6 cycles during maintenance period Route of Administration: oral or intravenous

Drug: ADI-PEG20; Investigational Medicine; Drug: Temozolomide; Radiotherapy and TMZ are standard front-line therapy for newly diagnosed GBM.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability of ADI-PEG 20 in combination with radiotherapy and TMZ [ Time Frame: Through study completion, 2.5 year anticipated ]

Secondary Outcome Measures :

1. Determine recommended phase 2 dose (RP2D) [ Time Frame: Through study completion, 2.5 year anticipated ]
   RP2D will be determined by 3+3 method, depending on the Dose-Limiting Toxicity (DLT).
2. Measure progression free survival at the RP2D [ Time Frame: Baseline brain MRI is after glioma surgery (if applicable) and prior to subject receiving the first ADI-PEG 20 administration. Scans are to be performed after 1, 3 and 6 months following completion of radiation therapy. ]
   Progression free survival was defined as the period of time from randomization to date of tumor progression or death. Tumor measurements must be noted and tumor response status by investigator should be calculated.
3. Measure overall survival at the RP2D [ Time Frame: Through study completion, 2.5 year anticipated ]
   Overall Survival was defined as the period of time from randomization to date of death due to any cause.
4. Minimum blood plasma concentration [Cmin ] of ADI-PEG 20 [ Time Frame: Blood samples to be collected bi-weekly for 11 weeks, then once every 4 weeks until week36. Sample will be collected prior to ADI-PEG 20 administration ]
   A pharmacokinetics measure of minimum ADI-PEG 20 concentration before the next ADI-PED 20 administration
5. Blood plasma level of arginine and citrulline [ Time Frame: Blood samples to be collected bi-weekly for 11 weeks, then once every 4 weeks until week36. Sample will be collected prior to ADI-PEG 20 administration ]
   Pharmacodynamics of ADI-PEG 20 in combination with radiotherapy and TMZ
6. Plasma levels of antibodies against ADI-PEG 20 [ Time Frame: Through study completion, 2.5 year anticipated ]
   Measurement of serum antibodies to ADI-PEG 20 to determine immunogenicity of ADI-PEG 20 in combination with radiotherapy and TMZ

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Newly diagnosed, histologically confirmed GBM WHO Grade IV (any wildtype or mutant or gene type, except gliosarcoma), non-resectable or partially resected or resected.
2. Age 20 - 75 years.
3. Karnofsky Performance Status (KPS) ≥ 60.
4. Expected life expectancy ≥16 weeks.
5. Stable or decreasing corticosteroids (5 mg/day dexamethasone or equivalent) within 5 days before the first dose of ADI-PEG 20.
6. No prior systemic therapy, immunotherapy, investigational agent, or radiation therapy.
7. Recovered from any prior surgery and no major surgery within 2 weeks of initiating treatment (other than GBM surgery). Surgery for placement of vascular access devices is acceptable.
8. Female subjects and male subjects must be asked to use appropriate contraception for both the male and female for the duration of the study. Male partners of female subjects and female partners of male subjects must agree to use two forms of contraception or agree to refrain from intercourse for the duration of the study if they are of childbearing potential. Females of childbearing potential must not be pregnant at the start of the study, and a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. If positive HCG pregnancy test, further evaluation to rule out pregnancy must be performed according to GCP before this subject is deemed eligible. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual period for at least 12 months).
9. Informed consent must be obtained prior to study initiation.
10. No concurrent investigational studies are allowed.
11. Absolute neutrophil count (ANC) ≥ 1500/μL.
12. Platelets ≥ 100,000/μL.
13. Serum uric acid ≤ 8 mg/dL (with or without medication control).
14. Creatinine clearance must be ≥ 40 mL/min/1.73 m2 (calculated using the Cockcroft-Gault equation: calculated creatinine clearance = (140-age (yrs)) × body weight (kg) (×0.85 if female) / 72 × serum creatinine (mg/dl).
15. Total bilirubin ≤ 2 x upper limit of normal.
16. ALT and AST ≤ 3 x upper limit of normal, unless liver metastases present then ≤ 5 x upper limit normal.

Exclusion Criteria:

1. Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
2. Pregnancy or lactation.
3. Expected non-compliance.
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness, social .
5. Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present or in the opinion of the investigator will not affect patient outcome.
6. Subjects who had been treated with ADI-PEG 20 previously.
7. History of uncontrolled seizure disorder not related to underlying cancer.
8. Known HIV positivity, or active hepatitis B infection, or active hepatitis C infection (testing not required).
9. Allergy to pegylated compounds.
10. Allergy to E. coli drug products (such as GMCSF).
11. Allergy to TMZ or any of its components.
12. History of hypersensitivity to dacarbazine.
13. Placement of Gliadel wafer at surgery.
14. Having a co-existing condition requiring systemic treatment with either corticosteroids or immunosuppressive medication.

Contacts and Locations

Contacts

Contact: John Bomalaski, M.D.; 858-452-6688 ext 114; jbomalaski@polarispharma.com

Locations

Taiwan

Chang Gung Memorial Hospital, Linkou Branch; Recruiting

Taoyuan, Taiwan, 333

Contact: Kuo-Chen Wei, M.D. 886-3-3281200 ext 2412 kuochenwei@cgmh.org.tw

Principal Investigator: Kuo-Chen Wei, M.D.

Sponsors and Collaborators

Polaris Group

Investigators

• Principal Investigator: Kuo-Chen Wei, M.D.; Chang Gung Memorial Hospital

More Information

• Responsible Party: Polaris Group
• ClinicalTrials.gov Identifier: NCT04587830
• Other Study ID Numbers: POLARIS2020-001
• First Posted: October 14, 2020
• Last Update Posted: September 30, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Polaris Group:

argininosuccinate synthetase; arginine; arginine deiminase

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Temozolomide; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents