Solid Tumors Clinical Trial
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
Status | Recruiting |
Enrollment | 20 |
Est. completion date | June 2024 |
Est. primary completion date | June 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 1 Year to 30 Years |
Eligibility | Inclusion 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: 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. 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 Exclusion Criteria: 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. |
Country | Name | City | State |
---|---|---|---|
United States | University of North Carolina at Chapel Hill - North Carolina Cancer Hospital | Chapel Hill | North Carolina |
United States | Atrium Health Levine Children's Hospital - Carolinas Medical Center | Charlotte | North Carolina |
United States | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio |
United States | Duke University Children's Hospital and Health Center | Durham | North Carolina |
United States | Indiana University School of Medicine, Riley Hospital for Children | Indianapolis | Indiana |
United States | Sarah Cannon Research Institute, Pediatric Hematology & Oncology | Nashville | Tennessee |
United States | UCSF, Mission Bay - Benioff Children's Hospital | San Francisco | California |
United States | Children's National Research Institute - Children's National Hospital | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
Valent Technologies, LLC |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Cmax | Maximum observed concentration of VAL-413 (Orotecan®) on Day 1 | 1 day | |
Secondary | Tmax | Time of observed VAL-413 (Orotecan®) Cmax on Day 1 | 1 day | |
Secondary | 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 | 1 day | |
Secondary | AUCinf | Area under the concentration-time curve for VAL-413 (Orotecan®) extrapolated to infinity on Day 1 | 1 day | |
Secondary | CL/F | Total oral body clearance at steady state calculated as VAL-413 (Orotecan®) dose/AUC on Day 1 | 1 day | |
Secondary | MRT | Mean Residence Time for VAL-413 (Orotecan®) calculated as AUMC/AUC where AUMC is Area under the Moment Curve | 1 day | |
Secondary | Vz | The apparent volume of distribution for VAL-413 (Orotecan®) during the terminal phase | 1 day | |
Secondary | 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 | 1 day | |
Secondary | T1/2 | Terminal elimination half-life of VAL-413 (Orotecan®) on Day 1 determined from 0.693/Lambda z | 1 day | |
Secondary | 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 | 1 month | |
Secondary | Adverse Events | To assess the toxicity profile of this combination therapy using NCI CTCAE guidelines | 17 months | |
Secondary | 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 | 17 months |
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