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

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ClinicalTrials.gov Identifier: NCT04525014
Recruitment Status : Not yet recruiting
First Posted : August 24, 2020
Last Update Posted : July 21, 2021
Sponsor:
Collaborator:
Texas Children's Cancer Center
Information provided by (Responsible Party):
EpicentRx, Inc.

Tracking Information
First Submitted Date  ICMJE August 20, 2020
First Posted Date  ICMJE August 24, 2020
Last Update Posted Date July 21, 2021
Estimated Study Start Date  ICMJE August 1, 2021
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2020)
Recommended phase 2 dose [ Time Frame: 18 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: August 21, 2020)
  • Grade 3 or higher CTCAE version 5.0 adverse event terms [ Time Frame: 18 months ]
    Describe the toxicities of RRx-001 in combination with irinotecan and temozolomide administered on this schedule in this population.
  • Progression-free survival (PFS) [ Time Frame: 15 months ]
    Describe the anti-tumor effects of RRx-001 in combination with irinotecan and temozolomide administered on this schedule in this population in the context of a Phase 1 trial.
  • Overall survival (OS) [ Time Frame: 15 months ]
    Describe the anti-tumor effects of RRx-001 in combination with irinotecan and temozolomide administered on this schedule in this population in the context of a Phase 1 trial.
  • Summarize tumor response rates [ Time Frame: 15 months ]
    Imaging-based evaluation is preferred to evaluation by clinical examination unless the lesion(s) being followed cannot be imaged but are assessable by clinical exam.
  • Change in tumor perfusion [ Time Frame: 15 months ]
    Measure treatment-induced change in tumor perfusion
  • Response correlation for change in tumor perfusion [ Time Frame: 15 months ]
    Correlation of change in tumor perfusion to matched patient's best treatment response
  • Change in cellularity [ Time Frame: 15 months ]
    Measure treatment-induced change in cellularity
  • Response correlation for change in cellularity [ Time Frame: 15 months ]
    Correlation of change in cellularity to matched patient's best treatment response
  • Ratio of M1 to M2 peripheral blood circulating monocytes [ Time Frame: 5 months ]
    Assess for change in the ratio of M1 to M2 peripheral blood circulating monocytes over the first 5 cycles of therapy.
  • Response correlation for ratio of M1 to M2 peripheral blood circulating monocytes [ Time Frame: 5 months ]
    Correlation of change in the ratio of M1 to M2 peripheral blood circulating monocytes over the first 5 cycles of therapy to matched patient's best treatment response.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE RRx-001 Given With Irinotecan and Temozolomide for Pediatric Patients With Recurrent or Progressive Malignant Solid and Central Nervous System Tumors
Official Title  ICMJE 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
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.
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Tumor, Recurrent
  • Brain Tumor, Pediatric
  • Central Nervous System Neoplasms
  • Unspecified Childhood Solid Tumor, Protocol Specific
Intervention  ICMJE
  • Drug: RRx-001
    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).
  • Drug: Temozolomide
    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
  • Drug: Irinotecan
    90 mg/m2 taken orally daily for 5 days administered 1 hour after temozolomide
Study Arms  ICMJE Experimental: RRx-001, Temozolomide and Irinotecan
Interventions:
  • Drug: RRx-001
  • Drug: Temozolomide
  • Drug: Irinotecan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 21, 2020)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Daniela Westerhold (832) 824-4552 diwester@texaschildrens.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04525014
Other Study ID Numbers  ICMJE H-45787
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party EpicentRx, Inc.
Study Sponsor  ICMJE EpicentRx, Inc.
Collaborators  ICMJE Texas Children's Cancer Center
Investigators  ICMJE
Study Director: Bryan Oronsky, MD EpicentRx, Inc.
Principal Investigator: Holly Lindsay, MD, MS Texas Children's Cancer Center
PRS Account EpicentRx, Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP