RECRUITING

Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors

Conditions

Solid Tumors Neuroblastoma Rhabdomyosarcoma Ewing Sarcoma Hepatoblastoma Medulloblastoma irinotecan pediatric solid tumor recurrent

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

A pilot pharmacokinetic trial to determine the safety and efficacy of a flavored, orally administered irinotecan VAL-413 (Orotecan®) given with temozolomide for treatment of recurrent pediatric solid tumors including but not limited to neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, hepatoblastoma and medulloblastoma

Official Title

Pilot Pharmacokinetic Study of VAL-413 (Orotecan®) in Patients With Recurrent Pediatric Solid Tumors

Quick Facts

Study Start:2021-10-25

Study Completion:2025-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04337177

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.

Ages Eligible for Study:1 Year to 30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
1. Patients must be 1 year of age to ≤ 30 years of age at the time of study entry. 2. Patients must have had histologic verification of a solid tumor or CNS tumor at either original diagnosis or relapse. 3. Measurable or evaluable disease is not required for enrollment on this safety/feasibility study. 4. Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life or for which irinotecan and/or temozolomide are acceptable therapeutic options based on existing standard of care available. 5. Karnofsky Performance Status ≥ 50% for patients \> 16 years of age and Lansky Performance Status ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 6. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraception method during and for 30 days after study treatment. (Abstinence is considered an acceptable method of effective contraception.) 7. Prior treatment with temozolomide, vincristine or irinotecan is allowed, although patients must not have had disease progression while receiving either irinotecan, vincristine or temozolomide. 8. Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, as described below: 1. Myelosuppressive chemotherapy: patients must not have received myelosuppressive chemotherapy within 21 days of first study treatment, but nitrosourea within 8 weeks (42 days) of first study treatment 2. Anti-cancer agents not known to be myelosuppressive (e.g., not associated with drops in platelet or neutrophil count): must not have received these therapies within 7 days of first study treatment, or at least 5 half-lives of the agent (whichever is longer) 3. Antibody therapy: At least 4 weeks must have elapsed since last antibody dose prior to first study treatment 4. Radiation therapy: At least two weeks must have elapsed since last local palliative radiation (small port) prior to first study treatment. At least 6 weeks must have elapsed if more substantial radiation was administered (e.g., \>50% pelvis, craniospinal, whole body), or therapeutic radiolabeled 131I MIBG or other radiopharmaceutical therapy. 5. High-Dose Chemotherapy with Autologous Stem Cell Transplant/Rescue: At least two months must have elapsed since receiving autologous hematopoietic stem cells prior to first study treatment. Patients who have had allogeneic transplants are ineligible. 6. Hematopoietic growth factors: must not have been received in the 14 days prior to first study treatment for a long-acting growth factor (e.g., pegfilgrastim), or 7 days prior to first study treatment for short-acting growth factor. 9. Peripheral absolute neutrophil count (ANC) ≥ 1,000/µL 10. Platelet count ≥100,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to first study treatment) 11. Hemoglobin ≥ 8.0 gm/dL (may receive RBC transfusions) NOTE: Patients with metastatic tumor in the bone marrow ARE eligible provided the above hematologic criteria are met. 12. Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m2 or Serum creatinine based on age/gender as follows: 13. Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age 14. SGPT (ALT) ≤ 5 x upper limit of normal (ULN) for age 15. Serum albumin ≥ 2 g/dL	1. Patients with a history of severe allergic reaction (e.g., more than simple rash) to dacarbazine or third-generation cephalosporins are ineligible. 2. Pregnant or breast-feeding women will not be entered on this study due to potential risks of fetal and teratogenic adverse events. A pregnancy test must be obtained prior to starting chemotherapy in post-menarchal female patients. 3. Patients who are currently receiving investigational drugs, or who have received an investigational drug within the last 7 days prior to first study treatment, are ineligible. 4. Patients who are currently receiving other anti-cancer agents are ineligible. 5. Patients taking strong inducers of CYP3A4, including but not limited to phenobarbital, phenytoin, carbamazepine, oxcarbazepine (Trileptal), rifampin, voriconazole, itraconazole, ketoconazole or other systemically-administered azole antifungal drugs, aprepitant (Emend) or St. John's Wort, in the 2 weeks prior to first study treatment are ineligible. 6. Patients taking strong inhibitors of CYP3A4 or UGT1A1 in the 1 week prior to first study treatment are ineligible. 7. Patients must not be receiving medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase activity. Medicines in this class are excluded, with the exception of acetaminophen. 8. Patients who have uncontrolled infections, require IV antibiotics at time of enrollment, or who are currently receiving treatment for Clostridium difficile infection are excluded. 9. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Inclusion Criteria

Exclusion Criteria

1. Patients must be 1 year of age to ≤ 30 years of age at the time of study entry.
2. Patients must have had histologic verification of a solid tumor or CNS tumor at either original diagnosis or relapse.
3. Measurable or evaluable disease is not required for enrollment on this safety/feasibility study.
4. Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life or for which irinotecan and/or temozolomide are acceptable therapeutic options based on existing standard of care available.
5. Karnofsky Performance Status ≥ 50% for patients \> 16 years of age and Lansky Performance Status ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
6. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraception method during and for 30 days after study treatment. (Abstinence is considered an acceptable method of effective contraception.)
7. Prior treatment with temozolomide, vincristine or irinotecan is allowed, although patients must not have had disease progression while receiving either irinotecan, vincristine or temozolomide.
8. Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, as described below:
1. Myelosuppressive chemotherapy: patients must not have received myelosuppressive chemotherapy within 21 days of first study treatment, but nitrosourea within 8 weeks (42 days) of first study treatment
2. Anti-cancer agents not known to be myelosuppressive (e.g., not associated with drops in platelet or neutrophil count): must not have received these therapies within 7 days of first study treatment, or at least 5 half-lives of the agent (whichever is longer)
3. Antibody therapy: At least 4 weeks must have elapsed since last antibody dose prior to first study treatment
4. Radiation therapy: At least two weeks must have elapsed since last local palliative radiation (small port) prior to first study treatment. At least 6 weeks must have elapsed if more substantial radiation was administered (e.g., \>50% pelvis, craniospinal, whole body), or therapeutic radiolabeled 131I MIBG or other radiopharmaceutical therapy.
5. High-Dose Chemotherapy with Autologous Stem Cell Transplant/Rescue: At least two months must have elapsed since receiving autologous hematopoietic stem cells prior to first study treatment. Patients who have had allogeneic transplants are ineligible.
6. Hematopoietic growth factors: must not have been received in the 14 days prior to first study treatment for a long-acting growth factor (e.g., pegfilgrastim), or 7 days prior to first study treatment for short-acting growth factor.
9. Peripheral absolute neutrophil count (ANC) ≥ 1,000/µL
10. Platelet count ≥100,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to first study treatment)
11. Hemoglobin ≥ 8.0 gm/dL (may receive RBC transfusions) NOTE: Patients with metastatic tumor in the bone marrow ARE eligible provided the above hematologic criteria are met.
12. Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m2 or Serum creatinine based on age/gender as follows:
13. Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
14. SGPT (ALT) ≤ 5 x upper limit of normal (ULN) for age
15. Serum albumin ≥ 2 g/dL

1. Patients with a history of severe allergic reaction (e.g., more than simple rash) to dacarbazine or third-generation cephalosporins are ineligible.
2. Pregnant or breast-feeding women will not be entered on this study due to potential risks of fetal and teratogenic adverse events. A pregnancy test must be obtained prior to starting chemotherapy in post-menarchal female patients.
3. Patients who are currently receiving investigational drugs, or who have received an investigational drug within the last 7 days prior to first study treatment, are ineligible.
4. Patients who are currently receiving other anti-cancer agents are ineligible.
5. Patients taking strong inducers of CYP3A4, including but not limited to phenobarbital, phenytoin, carbamazepine, oxcarbazepine (Trileptal), rifampin, voriconazole, itraconazole, ketoconazole or other systemically-administered azole antifungal drugs, aprepitant (Emend) or St. John's Wort, in the 2 weeks prior to first study treatment are ineligible.
6. Patients taking strong inhibitors of CYP3A4 or UGT1A1 in the 1 week prior to first study treatment are ineligible.
7. Patients must not be receiving medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase activity. Medicines in this class are excluded, with the exception of acetaminophen.
8. Patients who have uncontrolled infections, require IV antibiotics at time of enrollment, or who are currently receiving treatment for Clostridium difficile infection are excluded.
9. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Contacts and Locations

Study Contact

Neil Sankar, M.D.

CONTACT

(408) 215-1578

nsankar@valenttech.com

Lorena Lopez, B.S.

CONTACT

(925) 292-8360

llopez@solsentinel.com

Principal Investigator

Lars Wagner, M.D.

PRINCIPAL_INVESTIGATOR

Duke University Children's Hospital & Health Center

James Geller, M.D.

PRINCIPAL_INVESTIGATOR

Cincinnati Children's Hospital Medical Center (CCHMC)

Meghann McManus, D.O.

PRINCIPAL_INVESTIGATOR

Sarah Cannon Research Institute, Pediatric Hematology & Oncology

Javier Oesterheld, M.D.

PRINCIPAL_INVESTIGATOR

Atrium Health Levine Children's Hospital - Carolinas Medical Center

Patrick Thompson, M.D.

PRINCIPAL_INVESTIGATOR

UNC Chapel Hill - North Carolina Cancer Hospital

Aerang Kim, M.D.

PRINCIPAL_INVESTIGATOR

Children's National Hospital - Washington, DC

Kieuhoa Vo, M.D.

PRINCIPAL_INVESTIGATOR

UCSF - Mission Bay, Benioff Children's Hospital

Kyle Jackson, M.D.

PRINCIPAL_INVESTIGATOR

Indiana University School of Medicine, Riley Hospital for Children

Study Locations (Sites)

UCSF, Mission Bay - Benioff Children's Hospital

San Francisco, California, 94143

United States

Children's National Research Institute - Children's National Hospital

Washington, District of Columbia, 20010

United States

Indiana University School of Medicine, Riley Hospital for Children

Indianapolis, Indiana, 46202

United States

University of North Carolina at Chapel Hill - North Carolina Cancer Hospital

Chapel Hill, North Carolina, 27514

United States

Atrium Health Levine Children's Hospital - Carolinas Medical Center

Charlotte, North Carolina, 28204

United States

Duke University Children's Hospital and Health Center

Durham, North Carolina, 27710

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039

United States

Sarah Cannon Research Institute, Pediatric Hematology & Oncology

Nashville, Tennessee, 37203

United States

Collaborators and Investigators

Sponsor: Valent Technologies, LLC

Lars Wagner, M.D., PRINCIPAL_INVESTIGATOR, Duke University Children's Hospital & Health Center
James Geller, M.D., PRINCIPAL_INVESTIGATOR, Cincinnati Children's Hospital Medical Center (CCHMC)
Meghann McManus, D.O., PRINCIPAL_INVESTIGATOR, Sarah Cannon Research Institute, Pediatric Hematology & Oncology
Javier Oesterheld, M.D., PRINCIPAL_INVESTIGATOR, Atrium Health Levine Children's Hospital - Carolinas Medical Center
Patrick Thompson, M.D., PRINCIPAL_INVESTIGATOR, UNC Chapel Hill - North Carolina Cancer Hospital
Aerang Kim, M.D., PRINCIPAL_INVESTIGATOR, Children's National Hospital - Washington, DC
Kieuhoa Vo, M.D., PRINCIPAL_INVESTIGATOR, UCSF - Mission Bay, Benioff Children's Hospital
Kyle Jackson, M.D., PRINCIPAL_INVESTIGATOR, Indiana University School of Medicine, Riley Hospital for Children

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 Registration Dates

Study Start Date2021-10-25

Study Completion Date2025-06

Study Record Updates

Study Start Date2021-10-25

Study Completion Date2025-06

Terms related to this study

Keywords Provided by Researchers

irinotecan
pediatric
solid tumor
neuroblastoma
rhabdomyosarcoma
Ewing sarcoma
hepatoblastoma
medulloblastoma
recurrent

Additional Relevant MeSH Terms

Solid Tumors
Neuroblastoma
Rhabdomyosarcoma
Ewing Sarcoma
Hepatoblastoma
Medulloblastoma