- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04525014
RRx-001 Given With Irinotecan and Temozolomide for Pediatric Patients With Recurrent or Progressive Malignant Solid and Central Nervous System Tumors (PIRATE)
March 22, 2024 updated by: EpicentRx, Inc.
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
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Estimated)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Daniela Westerhold
- Phone Number: (832) 824-4552
- Email: diwester@texaschildrens.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Texas Children's Cancer Center
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year to 21 years (Child, Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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
- No evidence of dyspnea at rest
- Left ventricular ejection fraction > 50%
- 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.
- 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.
- 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.
- Patients must be able to safely take oral medications either as liquid or tablet.
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: RRx-001, Temozolomide and Irinotecan
|
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).
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
90 mg/m2 taken orally daily for 5 days administered 1 hour after temozolomide
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
18 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
18 months
|
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.
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15 months
|
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.
|
15 months
|
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.
|
15 months
|
Change in tumor perfusion
Time Frame: 15 months
|
Measure treatment-induced change in tumor perfusion
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15 months
|
Response correlation for change in tumor perfusion
Time Frame: 15 months
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Correlation of change in tumor perfusion to matched patient's best treatment response
|
15 months
|
Change in cellularity
Time Frame: 15 months
|
Measure treatment-induced change in cellularity
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15 months
|
Response correlation for change in cellularity
Time Frame: 15 months
|
Correlation of change in cellularity to matched patient's best treatment response
|
15 months
|
Ratio of M1 to M2 peripheral blood circulating monocytes
Time Frame: 5 months
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Assess for change in the ratio of M1 to M2 peripheral blood circulating monocytes over the first 5 cycles of therapy.
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5 months
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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.
|
5 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Bryan Oronsky, MD, EpicentRx, Inc.
- Principal Investigator: Stephanie Fetzko, MD, Texas Children's Cancer Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 26, 2023
Primary Completion (Estimated)
December 31, 2024
Study Completion (Estimated)
December 31, 2024
Study Registration Dates
First Submitted
August 20, 2020
First Submitted That Met QC Criteria
August 21, 2020
First Posted (Actual)
August 24, 2020
Study Record Updates
Last Update Posted (Actual)
March 26, 2024
Last Update Submitted That Met QC Criteria
March 22, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms by Site
- Disease Attributes
- Neoplasms
- Recurrence
- Brain Neoplasms
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Temozolomide
- Irinotecan
Other Study ID Numbers
- H-45787
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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