20 Participants Needed

Oral Irinotecan + Temozolomide for Pediatric Solid Cancers

Recruiting at 8 trial locations
LL
NS
Overseen ByNeil Sankar, M.D.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new flavored oral medicine called Orotecan® combined with temozolomide to treat children and young adults with recurring solid tumors. The treatment works by damaging the DNA of cancer cells to stop their growth. Temozolomide has been used in various trials for treating different types of tumors, including gliomas and medulloblastomas.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as strong inducers or inhibitors of specific enzymes (CYP3A4 and UGT1A1), and medications that affect platelet function. If you're on these, you may need to stop them 1-2 weeks before the trial.

Is the combination of oral Irinotecan and Temozolomide safe for pediatric solid cancers?

The combination of oral Irinotecan and Temozolomide has been studied in children with solid tumors, and some side effects have been noted, including diarrhea, low white blood cell counts (neutropenia), and low platelet counts (thrombocytopenia). These side effects can be serious, and the doses are being adjusted to find a safer balance.12345

What makes the drug combination of oral irinotecan and temozolomide unique for pediatric solid cancers?

This drug combination is unique because it uses oral administration of irinotecan, which is more convenient and less costly than intravenous methods, and it has shown effectiveness in treating difficult cases of pediatric solid tumors like neuroblastoma, Ewing's sarcoma, and rhabdomyosarcoma, where no standard treatment exists.13678

What data supports the effectiveness of the drug combination of oral irinotecan and temozolomide for pediatric solid cancers?

Research shows that the combination of irinotecan and temozolomide has been effective in treating refractory or relapsed pediatric solid tumors, including Ewing's sarcoma, neuroblastoma, and rhabdomyosarcoma. This combination has shown activity against these difficult-to-treat cancers, providing hope for improved outcomes.13679

Who Is on the Research Team?

Lars M. Wagner, MD | Pediatric ...

Lars Wagner, MD

Principal Investigator

Duke University Children's Hospital & Health Center

James Geller - Professor of Pediatrics ...

James Geller, MD

Principal Investigator

Cincinnati Children's Hospital Medical Center (CCHMC)

Javier E. Oesterheld, MD | Levine ...

Javier Oesterheld, M.D.

Principal Investigator

Atrium Health Levine Children's Hospital - Carolinas Medical Center

Patrick Thompson, MD | Department of ...

Patrick Thompson, M.D.

Principal Investigator

UNC Chapel Hill - North Carolina Cancer Hospital

AeRang Kim, MD, PHD - at Children's ...

AeRang Kim, MD, PhD

Principal Investigator

Children's National Hospital - Washington, DC

Dr. Kieuhoa T. Vo | UCSF Benioff ...

Kieuhoa T. Vo

Principal Investigator

UCSF - Mission Bay, Benioff Children's Hospital

MM

Meghann McManus, D.O.

Principal Investigator

Sarah Cannon Research Institute, Pediatric Hematology & Oncology

KJ

Kyle Jackson, M.D.

Principal Investigator

Indiana University School of Medicine, Riley Hospital for Children

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 to 30 with recurrent solid tumors like neuroblastoma or Ewing sarcoma. They must have a certain level of physical ability, no uncontrolled infections, not be pregnant, and agree to use contraception. Participants need normal organ function and can't join if they've had severe allergic reactions to specific drugs or are on certain medications.

Inclusion Criteria

My current cancer treatment options do not include a cure or significantly extend life with good quality.
I don't need to have measurable disease to join this study.
Peripheral absolute neutrophil count (ANC) ≥ 1,000/µL
See 23 more

Exclusion Criteria

I am not taking any medication that affects blood clotting, except for acetaminophen.
I have not taken strong medication inducers like phenobarbital or St. John's Wort in the last 2 weeks.
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.
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VAL-413 (Orotecan®) with Temozolomide for 5 consecutive days every 21-day cycle, up to 17 cycles

17 months
Visits on Day 1 of each cycle

Pharmacokinetic Assessment

Serum samples collected to characterize pharmacokinetic profiles of Orotecan® and conventional irinotecan

1 month
Samples collected on Days 1 and 4 during Cycle 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Temozolomide
  • VAL-413
Trial Overview The study tests the safety and effectiveness of a flavored oral form of Irinotecan (VAL-413) combined with Temozolomide in treating pediatric solid tumors. It's designed to see how well patients tolerate this new formulation and measure its impact on their cancer.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: 90 mg/m2/day VAL-413 (Orotecan®)Experimental Treatment2 Interventions
Group II: 75 mg/m2/day VAL-413 (Orotecan®)Experimental Treatment2 Interventions
Group III: 110 mg/m2/day VAL-413 (Orotecan®)Experimental Treatment2 Interventions

Temozolomide is already approved in European Union, United States for the following indications:

🇪🇺
Approved in European Union as Temodal for:
🇺🇸
Approved in United States as Temodar for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Valent Technologies, Inc.

Lead Sponsor

Trials
1
Recruited
20+

Valent Technologies, LLC

Lead Sponsor

Trials
1
Recruited
20+

Published Research Related to This Trial

In a study of 34 children with heavily pretreated refractory/relapsed solid tumors, the combination of vincristine, irinotecan, and temozolomide showed a 26.4% objective response rate, with particularly promising results in Ewing sarcoma patients (40% response).
The treatment was generally well tolerated, although diarrhea was a common side effect, with 10% of treatment courses resulting in severe cases (grade 3-4).
Vincristine, irinotecan, and temozolomide treatment for refractory/relapsed pediatric solid tumors: A single center experience.Büyükkapu Bay, S., Kebudi, R., Görgün, O., et al.[2019]
In a study of 32 pediatric patients with refractory or relapsed solid tumors, the combination of irinotecan and temozolomide resulted in a positive response in 33% of evaluable patients, with 2 achieving complete remission and 8 achieving partial remission.
The treatment was well tolerated, with only 28% of the 180 treatment cycles resulting in toxicity, and severe side effects (grade III-IV) occurring in just 8% of cases, indicating a favorable safety profile for this combination therapy.
[Irinotecan plus temozolomide in refractory or relapsed pediatric solid tumors].Hernández-Marqués, C., Lassaletta-Atienza, A., Ruiz Hernández, A., et al.[2018]
The maximum-tolerated dose (MTD) for the combination of temozolomide and irinotecan in pediatric patients with refractory solid tumors was determined to be 100 mg/m²/day of temozolomide and 10 mg/m²/day of irinotecan, with dose-limiting toxicities including severe diarrhea and infection observed at higher doses.
The treatment showed promising efficacy, with one complete response and two partial responses in patients with Ewing's sarcoma and neuroblastoma, particularly in those with low levels of a specific DNA repair protein, suggesting that this combination therapy could be effective for certain tumor types.
Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors.Wagner, LM., Crews, KR., Iacono, LC., et al.[2019]

Citations

Vincristine, irinotecan, and temozolomide treatment for refractory/relapsed pediatric solid tumors: A single center experience. [2019]
[Irinotecan plus temozolomide in refractory or relapsed pediatric solid tumors]. [2018]
Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors. [2019]
Phase I trial of oral irinotecan and temozolomide for children with relapsed high-risk neuroblastoma: a new approach to neuroblastoma therapy consortium study. [2021]
Temozolomide and irinotecan (TEMIRI regimen) as salvage treatment of irinotecan-sensitive advanced colorectal cancer patients bearing MGMT methylation. [2022]
Hematologic adverse events associated with temozolomide. [2018]
Phase I. Trial of irinotecan and temozolomide in patients with solid tumors. [2018]
Role of temozolomide in pediatric brain tumors. [2022]
Phase I trial of two schedules of vincristine, oral irinotecan, and temozolomide (VOIT) for children with relapsed or refractory solid tumors: a Children's Oncology Group phase I consortium study. [2021]
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