← Back to Search

Alkylating agents

Oral Irinotecan + Temozolomide for Pediatric Solid Cancers

Phase 1
Recruiting
Led By Kyle Jackson, M.D.
Research Sponsored by Valent Technologies, Inc.
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
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.
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.
Must not have
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 who have uncontrolled infections, require IV antibiotics at time of enrollment, or who are currently receiving treatment for Clostridium difficile infection are excluded
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 17 months
Awards & highlights

Summary

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.

Who is the study for?
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.
What is being tested?
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.
What are the potential side effects?
Possible side effects include digestive issues such as diarrhea, nausea, vomiting; lowered blood counts leading to increased infection risk; fatigue; liver problems indicated by altered blood tests; hair loss; and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
Select...
I am over 16 and can do most activities, or if under 16, I can do many activities without help.
Select...
My kidney function is within the required range for my age and gender.
Select...
I am between 1 and 30 years old.
Select...
My cancer was confirmed by a tissue test at diagnosis or relapse.
Select...
My liver enzyme ALT levels are within 5 times the normal limit.
Select...
My kidney function is within the normal range.
Select...
My cancer was confirmed by a tissue test at diagnosis or relapse.
Select...
My bilirubin levels are within the normal range for my age.
Select...
I haven't taken any cancer drugs that lower blood counts in the last 7 days or 5 half-lives.
Select...
I am between 1 and 30 years old.
Select...
It has been over 4 weeks since my last antibody therapy dose.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
Select...
I have not taken strong medication inducers like phenobarbital or St. John's Wort in the last 2 weeks.
Select...
I do not have an uncontrolled infection or need IV antibiotics.
Select...
I have never had a severe allergic reaction to dacarbazine or certain antibiotics.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~17 months
This trial's timeline: 3 weeks for screening, Varies for treatment, and 17 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Recommended Phase II Dose (RP2D)
Secondary study objectives
AUCinf
AUClast
Adverse Events
+9 more

Side effects data

From 2016 Phase 2 trial • 175 Patients • NCT01055314
36%
Febrile neutropenia
31%
Death NOS
30%
Diarrhea
22%
Pain
21%
Hyperglycemia
16%
Anorexia
16%
Infections and infestations - Other, specify
16%
Alanine aminotransferase increased
14%
Hypokalemia
13%
Nausea
11%
Hyponatremia
10%
Weight loss
9%
Mucositis oral
9%
Anemia
9%
Vomiting
9%
Aspartate aminotransferase increased
9%
Constipation
9%
Dehydration
9%
Hypophosphatemia
8%
Platelet count decreased
8%
Sepsis
7%
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
7%
Catheter related infection
7%
Colitis
7%
Abdominal pain
6%
Hypotension
6%
White blood cell decreased
6%
GGT increased
6%
Hypocalcemia
6%
Urinary retention
6%
Hypoalbuminemia
6%
Fever
5%
Typhlitis
5%
Anxiety
5%
Neutrophil count decreased
5%
Urinary tract infection
4%
Peripheral motor neuropathy
4%
Enterocolitis
4%
Lipase increased
4%
Pleural effusion
4%
Serum amylase increased
4%
Skin infection
4%
Epistaxis
4%
Urinary tract obstruction
3%
Blood bilirubin increased
3%
Lymphocyte count decreased
3%
Syncope
3%
Wound infection
3%
Dermatitis radiation
3%
Hypertension
3%
Sinus tachycardia
3%
Edema limbs
3%
Bone pain
3%
Dyspnea
3%
Hematuria
3%
Hypercalcemia
2%
Vulval infection
2%
Upper gastrointestinal hemorrhage
2%
Depressed level of consciousness
2%
Thromboembolic event
2%
Stridor
2%
Allergic reaction
2%
Back pain
2%
Lung infection
2%
Urticaria
2%
Acute kidney injury
2%
Muscle weakness lower limb
2%
Musculoskeletal and connective tissue disorder - Other, specify
2%
Pain in extremity
2%
Peripheral sensory neuropathy
2%
Proctitis
2%
Skin ulceration
2%
Apnea
2%
Stoma site infection
2%
Tumor pain
2%
Left ventricular systolic dysfunction
2%
Pancreatitis
2%
Portal hypertension
2%
Rectal hemorrhage
2%
Creatinine increased
2%
Enterocolitis infectious
2%
Hyperkalemia
2%
Investigations - Other, specify
2%
Abdominal distension
1%
Heart failure
1%
Penile pain
1%
Anal hemorrhage
1%
Ascites
1%
Bone marrow hypocellular
1%
Vasovagal reaction
1%
Hepatobiliary disorders - Other, specify
1%
Gastrointestinal disorders - Other, specify
1%
Soft tissue infection
1%
Delirium
1%
Tracheitis
1%
Seizure
1%
Esophageal pain
1%
Anal mucositis
1%
Menorrhagia
1%
Sore throat
1%
Anaphylaxis
1%
Vascular disorders - Other, specify
1%
Fracture
1%
Hydrocephalus
1%
Device related infection
1%
Tooth infection
1%
Gastric ulcer
1%
Sinusitis
1%
Skin and subcutaneous tissue disorders - Other, specify
1%
Pharyngitis
1%
Pyramidal tract syndrome
1%
Anal ulcer
1%
Depression
1%
Ejection fraction decreased
1%
Rash maculo-papular
1%
Pruritus
1%
Myositis
1%
Nail infection
1%
Pain of skin
1%
Pleuritic pain
1%
Pneumonitis
1%
Pneumothorax
1%
Postoperative hemorrhage
1%
Renal and urinary disorders - Other, specify
1%
Respiratory, thoracic and mediastinal disorders - Other, specify
1%
Salivary duct inflammation
1%
Small intestine infection
1%
Alkaline phosphatase increased
1%
Appendicitis
1%
Spinal fracture
1%
Disseminated intravascular coagulation
1%
Ear and labyrinth disorders - Other, specify
1%
Endocrine disorders - Other, specify
1%
Esophageal stenosis
1%
Esophagitis
1%
Gastric hemorrhage
1%
Gum infection
1%
Tumor lysis syndrome
1%
Upper respiratory infection
1%
Hypertriglyceridemia
1%
Hypoxia
1%
Ileus
1%
INR increased
1%
Laryngeal edema
1%
Multi-organ failure
1%
Myelodysplastic syndrome
1%
Oral hemorrhage
1%
Oral pain
1%
Pulmonary edema
1%
Rectal fistula
1%
Rectal pain
1%
Respiratory failure
1%
Bladder spasm
1%
Chest wall pain
1%
Confusion
1%
Congenital, familial and genetic disorders - Other, specify
1%
CPK increased
1%
Dizziness
1%
Encephalopathy
1%
Eye disorders - Other, specify
1%
Generalized muscle weakness
1%
Hoarseness
1%
Hypernatremia
1%
Hypoglycemia
1%
Hypomagnesemia
1%
Insomnia
1%
Irregular menstruation
1%
Irritability
1%
Joint range of motion decreased cervical spine
1%
Kyphosis
1%
Lethargy
1%
Headache
1%
Laryngeal mucositis
1%
Pelvic pain
1%
Esophageal infection
1%
Abdominal infection
1%
Acidosis
1%
Anal fistula
1%
Fall
1%
Fatigue
1%
Gait disturbance
100%
80%
60%
40%
20%
0%
Study treatment Arm
Group 1 (Chemotherapy, Radiation Therapy, Cixutumumab)
Group 2 (Chemotherapy, Radiation Therapy, Temozolomide)

Trial Design

3Treatment groups
Experimental Treatment
Group I: 90 mg/m2/day VAL-413 (Orotecan®)Experimental Treatment2 Interventions
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.
Group II: 75 mg/m2/day VAL-413 (Orotecan®)Experimental Treatment2 Interventions
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.
Group III: 110 mg/m2/day VAL-413 (Orotecan®)Experimental Treatment2 Interventions
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.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Temozolomide
2010
Completed Phase 3
~1880

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Irinotecan, a topoisomerase I inhibitor, works by preventing the relaxation of DNA supercoiling, which is necessary for DNA replication and transcription. This leads to DNA damage and cell death, particularly in rapidly dividing cancer cells like those in neuroblastoma. Temozolomide, an alkylating agent, adds alkyl groups to DNA, causing DNA cross-linking and strand breaks, which also result in cell death. These mechanisms are crucial for neuroblastoma patients because they target the cancer cells' ability to proliferate, thereby reducing tumor growth and potentially improving patient outcomes.
Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26.

Find a Location

Who is running the clinical trial?

Valent Technologies, Inc.Lead Sponsor
Valent Technologies, LLCLead Sponsor
Kyle Jackson, M.D.Principal InvestigatorIndiana University School of Medicine, Riley Hospital for Children

Media Library

Temozolomide (Alkylating agents) Clinical Trial Eligibility Overview. Trial Name: NCT04337177 — Phase 1
Neuroblastoma Research Study Groups: 75 mg/m2/day VAL-413 (Orotecan®), 110 mg/m2/day VAL-413 (Orotecan®), 90 mg/m2/day VAL-413 (Orotecan®)
Neuroblastoma Clinical Trial 2023: Temozolomide Highlights & Side Effects. Trial Name: NCT04337177 — Phase 1
Temozolomide (Alkylating agents) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04337177 — Phase 1
~5 spots leftby Oct 2025