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

NCT04337177 | Recruiting Phase 1 FDA Drug

• 1 other identifier: VAL-10-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 8

Brief Summary

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

Conditions

Solid Tumors; Neuroblastoma; Rhabdomyosarcoma; Ewing Sarcoma; Hepatoblastoma; Medulloblastoma

Keywords

irinotecan; pediatric; solid tumor; neuroblastoma; rhabdomyosarcoma; Ewing sarcoma; hepatoblastoma; medulloblastoma; recurrent

Outcome Measures

Primary Outcomes (1)

• Recommended Phase II Dose (RP2D)

  To establish the recommended Phase II dose of a flavored preparation of orally administered irinotecan VAL-413 (Orotecan®) when given in combination with temozolomide for 5 consecutive days

  17 months

Secondary Outcomes (12)

• Cmax

  1 day

• Tmax

  1 day

• AUClast

  1 day

• AUCinf

  1 day

• CL/F

  1 day

Study Arms (3)

90 mg/m2/day VAL-413 (Orotecan®)

EXPERIMENTAL

Orotecan® at 90 mg/m2/day administered with Temozolomide at 100 mg/m2/day orally for 5 consecutive days at the beginning of every 21-day cycle. A single dose of the intravenous preparation of irinotecan taken orally (IRN-IVPO) will be substituted at the same dosage as Orotecan® for during Cycle 1.

Drug: VAL-413; Drug: Temozolomide

110 mg/m2/day VAL-413 (Orotecan®)

EXPERIMENTAL

Orotecan® at 110 mg/m2/day administered with Temozolomide at 100 mg/m2/day orally for 5 consecutive days at the beginning of every 21-day cycle. A single dose of the intravenous preparation of irinotecan taken orally (IRN-IVPO) will be substituted at the same dosage as Orotecan® for during Cycle 1.

Drug: VAL-413; Drug: Temozolomide

75 mg/m2/day VAL-413 (Orotecan®)

EXPERIMENTAL

In the event the 90 mg/m2/day starting dose is not tolerable due to toxicity, a lower starting dose of 75 mg/m2/day may be implemented. Orotecan® at 75 mg/m2/day administered with Temozolomide at 100 mg/m2/day orally for 5 consecutive days at the beginning of every 21-day cycle. A single dose of the intravenous preparation of irinotecan taken orally (IRN-IVPO) will be substituted at the same dosage as Orotecan® for during Cycle 1.

Drug: VAL-413; Drug: Temozolomide

Interventions

VAL-413 DRUG

a flavored preparation of orally administered irinotecan

Also known as: Orotecan®

110 mg/m2/day VAL-413 (Orotecan®); 75 mg/m2/day VAL-413 (Orotecan®); 90 mg/m2/day VAL-413 (Orotecan®)

Temozolomide DRUG

alkylating oral chemotherapy agent used to treatment brain cancers

Also known as: Temodar, Temodal, Temcad, TMZ

110 mg/m2/day VAL-413 (Orotecan®); 75 mg/m2/day VAL-413 (Orotecan®); 90 mg/m2/day VAL-413 (Orotecan®)

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be 1 year of age to ≤ 30 years of age at the time of study entry.
• Patients must have had histologic verification of a solid tumor or CNS tumor at either original diagnosis or relapse.
• Measurable or evaluable disease is not required for enrollment on this safety/feasibility study.
• 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.
• 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.
• 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.)
• Prior treatment with temozolomide, vincristine or irinotecan is allowed, although patients must not have had disease progression while receiving either irinotecan, vincristine or temozolomide.
• Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, as described below:
• 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
• 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)
• Antibody therapy: At least 4 weeks must have elapsed since last antibody dose prior to first study treatment
• 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.
• 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.
• 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.
• Peripheral absolute neutrophil count (ANC) ≥ 1,000/µL

You may not qualify if:

• Patients with a history of severe allergic reaction (e.g., more than simple rash) to dacarbazine or third-generation cephalosporins are ineligible.
• 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.
• 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.
• Patients who are currently receiving other anti-cancer agents are ineligible.
• 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.
• Patients taking strong inhibitors of CYP3A4 or UGT1A1 in the 1 week prior to first study treatment are ineligible.
• 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.
• Patients who have uncontrolled infections, require IV antibiotics at time of enrollment, or who are currently receiving treatment for Clostridium difficile infection are excluded.
• 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.

Sponsors & Collaborators

• Valent Technologies, LLC: lead

Study Sites (8)

UCSF, Mission Bay - Benioff Children's Hospital

San Francisco, California, 94143, United States

RECRUITING

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

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Indiana University School of Medicine, Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

RECRUITING

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

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Atrium Health Levine Children's Hospital - Carolinas Medical Center

Charlotte, North Carolina, 28204, United States

RECRUITING

Duke University Children's Hospital and Health Center

Durham, North Carolina, 27710, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

RECRUITING

Sarah Cannon Research Institute, Pediatric Hematology & Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Rhabdomyosarcoma; Sarcoma, Ewing; Hepatoblastoma; Medulloblastoma; Recurrence

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Complex and Mixed; Glioma; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Lars Wagner, M.D.

  Duke University Children's Hospital & Health Center

  PRINCIPAL INVESTIGATOR

• James Geller, M.D.

  Cincinnati Children's Hospital Medical Center (CCHMC)

  PRINCIPAL INVESTIGATOR

• Meghann McManus, D.O.

  Sarah Cannon Research Institute, Pediatric Hematology & Oncology

  PRINCIPAL INVESTIGATOR

• Javier Oesterheld, M.D.

  Atrium Health Levine Children's Hospital - Carolinas Medical Center

  PRINCIPAL INVESTIGATOR

• Patrick Thompson, M.D.

  UNC Chapel Hill - North Carolina Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Aerang Kim, M.D.

  Children's National Hospital - Washington, DC

  PRINCIPAL INVESTIGATOR

• Kieuhoa Vo, M.D.

  UCSF - Mission Bay, Benioff Children's Hospital

  PRINCIPAL INVESTIGATOR

• Kyle Jackson, M.D.

  Indiana University School of Medicine, Riley Hospital for Children

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Neil Sankar, M.D.

CONTACT

(408) 215-1578; nsankar@valenttech.com

Lorena Lopez, B.S.

CONTACT

(925) 292-8360; llopez@solsentinel.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two different dose levels of VAL-413 (Orotecan®) will be studied in combination with fixed-dose temozolomide using a standard 3 + 3 phase I design. The first three patients will receive temozolomide in combination with Orotecan® at 90 mg/m2/day, which is the standard dose of irinotecan. If no dose-limiting toxicity (DLT) occurs during Cycle 1 in these patients, then subsequent patients will start Cycle 1 using a Orotecan® dose of 110 mg/m2/day. In the event the starting dose of 90 mg/m2/day is not tolerable due to toxicity, a lower starting dose of 75 mg/m2/day may be implemented.

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 7, 2020
• Study Start: October 25, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)