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Solid TumorsPhase 1NCT04337177

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

A Phase 1 study testing VAL-413 and Temozolomide in people with Solid Tumors and Neuroblastoma, run by Valent Technologies, LLC at 11 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 1 year to 30 years
Conditions the study is for
Solid Tumors, Neuroblastoma, Rhabdomyosarcoma
What is being tested?
VAL-413 and Temozolomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
11 sitesUnited States
Study dates
25 Oct 2021to Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.)
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  • 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
  • Platelet count ≥100,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to first study treatment)
  • 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.
  • Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m2 or Serum creatinine based on age/gender as follows:
  • Age Maximum Serum Creatinine (mg/dL) Male Female 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
  • ≥ 16 years 1.7 1.4
  • The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • SGPT (ALT) ≤ 5 x upper limit of normal (ULN) for age
  • Serum albumin ≥ 2 g/dL

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Children's Healthcare of Atlanta - Arthur M. Blank Hospital

    Atlanta, Georgia, 30329

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

    Chapel Hill, North Carolina, 27514

  • Atrium Health Levine Children's Hospital - Carolinas Medical Center

    Charlotte, North Carolina, 28204

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Duke University Children's Hospital and Health Center

    Durham, North Carolina, 27710

  • Indiana University School of Medicine, Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Sarah Cannon Research Institute, Pediatric Hematology & Oncology

    Nashville, Tennessee, 37203

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • UCSF, Mission Bay - Benioff Children's Hospital

    San Francisco, California, 94143

  • Washington University - St. Louis

    St Louis, Missouri, 63110

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

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

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

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

Read the detailed description

Up to 20 patients ≥ 1 year of age or ≤ 30 years of age with recurrent pediatric solid tumors will be enrolled. During the first cycle of treatment, each patient will receive 4 daily doses of VAL-413 (Orotecan®) and one daily dose of the intravenous preparation of irinotecan taken orally (IRN-IVPO), together with 5 days of concurrent temozolomide. During all subsequent cycles, only Orotecan® will be given with temozolomide in 5 day courses administered every 21 days as tolerated.

The dosing regimen in this study will be Temozolomide at 100 mg/m2/day with Orotecan® at either 90 or 110mg/m2/day, administered orally for 5 consecutive days at the beginning of every 21-day cycle. A single dose of IRN-IVPO will be substituted at the same dosage as Orotecan® during Cycle 1. Up to 17 cycles of treatment may be administered on this study.

Data collected from this study will allow for an assessment of Orotecan® safety and efficacy. Interval medical histories, targeted physical exams, complete blood counts, and other laboratory and safety assessments will be performed at Day 1 of each treatment cycle for all study subjects. At baseline and during study, disease status will be assessed by appropriate clinical and imaging evaluation (CT, MRI, or PET) and using Response Evaluation Criteria in Solid Tumors (RECIST), International Neuroblastoma Response Criteria (INRC) for patients with neuroblastoma, or the Children's Oncology Group Response Criteria for CNS tumors. In addition, a single-response taste survey will be conducted on Day 1 and Day 4 of the first cycle, which will allow patients to evaluate the taste of Orotecan®. Serum samples will be collected at various time points on Days 1 and 4 during Cycle 1 to characterize and compare the pharmacokinetic profiles of Orotecan® and conventional irinotecan given orally.

Assessment of first-cycle toxicity will be used to identify the recommended phase II dose for Orotecan®. Toxicity will be evaluated and documented using NCI CTCAE guidelines. The recommended Phase II dose will be identified as the highest dose at which no more than 1 of 6 patients experiences a first cycle dose limiting toxicity (DLT). Additional study subjects may be enrolled at the recommended Phase II dose to ensure balanced safety and pharmacokinetic data is obtained for at least 3 patients < 12 years old and at least 3 patients > 12 years old.

Being tested
VAL-413, Temozolomide
Keywords
irinotecan, pediatric, solid tumor, neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, hepatoblastoma, medulloblastoma, recurrent
Medical subject headings
Neuroblastoma, Rhabdomyosarcoma, Sarcoma, Ewing, Hepatoblastoma, Medulloblastoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VAL-413Drug

    Also called Orotecan®

    a flavored preparation of orally administered irinotecan

  • TemozolomideDrug

    Also called Temodar, Temodal, Temcad, TMZ

    alkylating oral chemotherapy agent used to treatment brain cancers

Study groups in NCT04337177
Study groupRoleWhat they receive
90 mg/m2/day VAL-413 (Orotecan®)ExperimentalOrotecan® 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.
Receives: Drug: VAL-413; Drug: Temozolomide
110 mg/m2/day VAL-413 (Orotecan®)ExperimentalOrotecan® 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.
Receives: Drug: VAL-413; Drug: Temozolomide
75 mg/m2/day VAL-413 (Orotecan®)ExperimentalIn 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.
Receives: Drug: VAL-413; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 17 months

Secondary outcomes (12)

  1. Cmax

    Maximum observed concentration of VAL-413 (Orotecan®) on Day 1

    Measured: 1 day

  2. Tmax

    Time of observed VAL-413 (Orotecan®) Cmax on Day 1

    Measured: 1 day

  3. AUClast

    Area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable VAL-413 (Orotecan®) concentration on Day 1

    Measured: 1 day

  4. AUCinf

    Area under the concentration-time curve for VAL-413 (Orotecan®) extrapolated to infinity on Day 1

    Measured: 1 day

  5. CL/F

    Total oral body clearance at steady state calculated as VAL-413 (Orotecan®) dose/AUC on Day 1

    Measured: 1 day

  6. MRT

    Mean Residence Time for VAL-413 (Orotecan®) calculated as AUMC/AUC where AUMC is Area under the Moment Curve

    Measured: 1 day

  7. Vz

    The apparent volume of distribution for VAL-413 (Orotecan®) during the terminal phase

    Measured: 1 day

  8. Lambda z

    The terminal elimination rate constant determined by selection of at least three decreasing data points on the terminal phase of the concentration time curve for VAL-413 (Orotecan®) on Day 1

    Measured: 1 day

  9. T1/2

    Terminal elimination half-life of VAL-413 (Orotecan®) on Day 1 determined from 0.693/Lambda z

    Measured: 1 day

  10. Palatability

    To evaluate the palatability of VAL-413 (Orotecan®) using a proprietary Valent Taste Survey which allows pediatric patients or their parents to rate how agreeable they find the flavor of VAL-413 (Orotecan®), on scale from 7, Like Very Much down to 1, Dislike Very Much

    Measured: 1 month

  11. Adverse Events

    To assess the toxicity profile of this combination therapy using NCI CTCAE guidelines

    Measured: 17 months

  12. Treatment Response

    To assess treatment response using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline, or for patients with neuroblastoma, the International Neuroblastoma Response Criteria (INRC) guideline

    Measured: 17 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2020
  2. Study start25 Oct 2021
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04337177
Sponsor's protocol ID
VAL-10-001
Status last verified
Jul 2026
First submitted
30 Mar 2020
Last updated
30 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing VAL-413 and Temozolomide in people with Solid Tumors and Neuroblastoma, run by Valent Technologies, LLC at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended Phase II Dose (RP2D) (time frame: 17 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04337177.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.

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