Clinical Trials /

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

NCT04525014

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: RRx-001 Given With Irinotecan and Temozolomide for Pediatric Patients With Recurrent or Progressive Malignant Solid and Central Nervous System Tumors
  • Official Title: A Phase 1 Trial of RRx-001 in Combination With Irinotecan and Temozolomide for Pediatric Patients With Recurrent or Progressive Malignant Solid and Central Nervous System Tumors

Clinical Trial IDs

  • ORG STUDY ID: H-45787
  • NCT ID: NCT04525014

Conditions

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

Interventions

DrugSynonymsArms
RRx-001RRx-001, Temozolomide and Irinotecan
TemozolomideRRx-001, Temozolomide and Irinotecan
IrinotecanRRx-001, Temozolomide and Irinotecan

Purpose

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.

Detailed Description

      The goals of the PIRATE study are:

        -  Determine if the adult dose of RRx-001 is safe when given together with 2 chemotherapy
           drugs called irinotecan and temozolomide in children and young adults with
           previously-treated cancerous tumors

        -  Determine the side effects of RRx-001 in children and young adults when given together
           with irinotecan and temozolomide

        -  Understand if the combination of RRx-001, irinotecan, and temozolomide is helpful for
           children and young adults with previously-treated cancerous tumors

        -  In patients with brain tumors, measure if RRx-001 causes changes in the tumor on
           Magnetic Resonance Imaging (MRI)

        -  Determine if RRx-001 causes changes in the immune system which may help the body
           naturally fight the tumor
    

Trial Arms

NameTypeDescriptionInterventions
RRx-001, Temozolomide and IrinotecanExperimental
  • RRx-001
  • Temozolomide
  • Irinotecan

Eligibility Criteria

        Inclusion Criteria:

          1. Recurrent or progressive malignant (World Health Organization (WHO) grade 3 or 4
             tumors) primary brain or spinal cord tumors and solid tumors (excluding lymphomas)

          2. 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.

          3. Patients must have a Karnofsky score of ≥50% if >16 years old or a Lansky score of ≥50
             if ≤16 years old

          4. 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.

          5. 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.

          6. 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.

          7. 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.

          8. 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.

          9. Peripheral absolute neutrophil count ≥1000/mm3

         10. Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥50 mL/min/1.73
             m2 or a serum creatinine based on age and sex

         11. Conjugated bilirubin ≤1.5 times the institutional laboratory's upper limit of normal

         12. Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) ≤3 times
             the institutional laboratory's upper limit of normal

         13. Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) ≤3 times
             the institutional laboratory's upper limit of normal

         14. Adequate pulmonary function defined as:

         15. Oxygen saturation as measured by pulse oximetry > 93% on room air

         16. No evidence of dyspnea at rest

         17. Left ventricular ejection fraction > 50%

         18. Patients of child-bearing potential of both genders must utilize contraception
             including but not limited to hormonal contraception, barrier method, or abstinence for
             the duration of the study and 28 days after completion of study.

         19. Patients must have a central line in place prior to administration of the first dose
             of RRx-001. Patients must have fully recovered from all acute effects of central line
             placement prior to initiation of study treatment.

         20. The patient or parent/legally authorized representative is able to understand the
             consent and is willing to sign a written informed consent document according to
             institutional guidelines. Assent, when appropriate, will be obtained according to
             institutional guidelines.

         21. Patients must be able to safely take oral medications either as liquid or tablet.

        Exclusion Criteria:

          1. Pregnant or breast feeding females

          2. 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.

          3. Patients taking concurrent anti-cancer or investigational drug therapies are not
             eligible for study enrollment.

          4. 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.

          5. While on study, concomitant use of clozapine, echinacea, leflunomide, natalizumab, and
             tofacitinib are prohibited due to potential for increased temozolomide toxicity.

          6. Patients who have received drugs that are strong inducers of CYP3A4 within 14 days
             prior to study enrollment are not eligible.

          7. 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.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended phase 2 dose
Time Frame:18 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:EpicentRx, Inc.

Trial Keywords

  • Brain cancer
  • Pediatric cancer
  • Spinal cord tumor
  • Solid tumor

Last Updated

August 21, 2020