RRx-001 Given With Irinotecan and Temozolomide for Pediatric Patients With Recurrent or Progressive Malignant Solid and Central Nervous System Tumors

NCT04525014 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: H-45787
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The PIRATE study tests the experimental drug RRx-001 in combination with 2 chemotherapy drugs that are commonly used in patients with cancer. RRx-001 has been used alone and with other anti-cancer medicines in adults. However, the investigators do not know what effects it will have in children and young adults.

Conditions

Brain Tumor, Recurrent; Brain Tumor, Pediatric; Central Nervous System Neoplasms; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

Brain cancer; Pediatric cancer; Spinal cord tumor; Solid tumor

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose

  Estimate the recommended phase 2 dose of RRx-001 administered every 3 weeks as an IV infusion in combination with oral irinotecan and temozolomide in pediatric patients with recurrent or progressive malignant solid or central nervous system (CNS) tumors.

  18 months

Other Outcomes (10)

• Grade 3 or higher CTCAE version 5.0 adverse event terms

  18 months

• Progression-free survival (PFS)

  15 months

• Overall survival (OS)

  15 months

Study Arms (1)

RRx-001, Temozolomide and Irinotecan

EXPERIMENTAL

Drug: RRx-001; Drug: Temozolomide; Drug: Irinotecan

Interventions

RRx-001 DRUG

RRx-001 will be administered every 3 weeks via intravenous infusion at three dose levels: 0.5 mg/m2 (Max 1 mg), 1 mg/m2 (Max 2 mg), and 2 mg/m2 (Max 4 mg).

RRx-001, Temozolomide and Irinotecan

Temozolomide DRUG

100 mg/m2 (children ≥0.5 m2) or 3 mg/kg (children \<0.5 m2) daily for 5 days beginning on day 1 of each cycle

RRx-001, Temozolomide and Irinotecan

Irinotecan DRUG

90 mg/m2 taken orally daily for 5 days administered 1 hour after temozolomide

RRx-001, Temozolomide and Irinotecan

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Recurrent or progressive malignant (World Health Organization (WHO) grade 3 or 4 tumors) primary brain or spinal cord tumors and solid tumors (excluding lymphomas)
• Eligible patients may have measureable or non-measurable but evaluable disease according to the reviewed Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 criteria.
• Patients must have a Karnofsky score of ≥50% if \>16 years old or a Lansky score of ≥50 if ≤16 years old
• Patients must have fully recovered from the acute treatment-related toxicities (defined as \<grade 1) of their most recent prior anti-neoplastic therapy prior to study enrollment.
• Patients must be at least 4 weeks from major surgery including craniotomy or tumor debulking/resection and at least 1 week from stereotactic biopsy prior to study enrollment. Patients must have fully recovered from all acute effects of prior surgical intervention excluding central line placement prior to study enrollment. Patients must have fully recovered from all acute effects of central line placement prior to initiation of study treatment.
• Patients with neurological deficits should have deficits that are stable for a minimum of 7 days prior to study enrollment. Patients with seizure disorders may be enrolled if the seizures are well-controlled with a stable seizure frequency and duration for a minimum 7 days.
• Patients on chronic systemic steroids must be on a stable or decreasing dose for at least 7 days prior to study enrollment. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid.
• Platelet count ≥75,000/mm3. Patient must be transfusion independent defined as not receiving platelet transfusions with a 7-day period prior to study enrollment.
• Peripheral absolute neutrophil count ≥1000/mm3
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 or a serum creatinine based on age and sex
• Conjugated bilirubin ≤1.5 times the institutional laboratory's upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) ≤3 times the institutional laboratory's upper limit of normal
• Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) ≤3 times the institutional laboratory's upper limit of normal
• Adequate pulmonary function defined as:
• Oxygen saturation as measured by pulse oximetry \> 93% on room air

You may not qualify if:

• Pregnant or breast feeding females
• Patients with the following conditions will be excluded from study enrollment: cyanotic heart disease, intermediate or severe β-thalassemia, known glucose-6-phosphate dehydrogenase (G6PD) deficiency, active infections, concurrent malignancy, a known thrombophilia syndrome, or a personal history of venous thromboembolism including catheter-associated thrombi.31-34 Additionally, patients with clinically significant or poorly controlled cardiac, pulmonary, hepatic, or other organ dysfunction that, in the opinion of the investigator, would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity, or interfere with the study procedures or results are not eligible for study enrollment. Patients with a known coagulopathy or bleeding diathesis or who have undergone either a solid organ or allogeneic bone marrow/stem cell transplant are not eligible for study enrollment.
• Patients taking concurrent anti-cancer or investigational drug therapies are not eligible for study enrollment.
• Patients taking anti-oxidants including alpha lipoic acid, vitamin E, N- acetylcysteine, and omega 3 fatty acid supplements are not eligible for study enrollment. Patients must be off these drugs for a minimum of 7 days prior to study enrollment and must remain off anti-oxidant medications for the duration of study treatment.
• While on study, concomitant use of clozapine, echinacea, leflunomide, natalizumab, and tofacitinib are prohibited due to potential for increased temozolomide toxicity.
• Patients who have received drugs that are strong inducers of CYP3A4 within 14 days prior to study enrollment are not eligible.
• Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to drug administration plan, other study procedures, and study restrictions are not eligible for study enrollment.

Sponsors & Collaborators

• EpicentRx, Inc.: lead
• Texas Children's Cancer Center: collaborator

Study Sites (1)

Texas Children's Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Central Nervous System Neoplasms; Neoplasms; Spinal Cord Neoplasms

Interventions

RRx-001; Temozolomide; Irinotecan

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Study Officials

• Bryan Oronsky, MD

  EpicentRx, Inc.

  STUDY DIRECTOR

• Stephanie Fetzko, MD

  Texas Children's Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: August 24, 2020
• Study Start: January 26, 2023
• Primary Completion: July 29, 2024
• Study Completion: July 29, 2024
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)