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New treatment option for Advanced Cancer
Official title A Study of Repotrectinib in Combination With Chemotherapy in Children and Young Adults With Solid Tumor Cancer
ClinicalTrials.gov ID: NCT05004116
What this study is testing
What is Repotrectinib?
Repotrectinib is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for advanced cancer.
Also referred to as TPX-0005.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This study will test the safety of the study drug, repotrectinib, in combination with chemotherapy (irinotecan and temozolomide) in children and young adults who have advanced or metastatic solid tumors. We researchers will try to find the highest dose of the study drug that causes few or mild side effects in study participants.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 1 to 25
You may be able to join if
- (ALL Patients) :
- Prior Therapy: Patients must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy prior to...
- Myelosuppressive chemotherapy: Last dose was given at least 21 days before the start date for protocol therapy.
- Biologic (anti-neoplastic agent including retinoids): Last dose given at least 7 days prior to the start date for protocol therapy.
- Monoclonal antibodies: Last dose of any monoclonal antibodies must have received at least 7 days or 3 half-lives, whichever is longer, prior to the...
You likely can't join if
- Phase 1- patients with known bone marrow disease
- Concurrent participation in another therapeutic clinical trial
- Major surgery within 14 days (2 weeks) prior to C1D1. Central venous access (Broviac, MediPort) placement does not meet criteria for major surgery.
- Pregnancy or lactation
- Known active systemic infections requiring ongoing treatment (bacterial, fungal, viral including human immunodeficiency virus positivity). Skin or...
- Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) or other malabsorption syndromes that would impact on drug...
See the full eligibility criteria
Who can join
- (ALL Patients) :
- Prior Therapy: Patients must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy prior to study enrollment. Patients must not have received the therapies...
- Myelosuppressive chemotherapy: Last dose was given at least 21 days before the start date for protocol therapy.
- Biologic (anti-neoplastic agent including retinoids): Last dose given at least 7 days prior to the start date for protocol therapy.
- Monoclonal antibodies: Last dose of any monoclonal antibodies must have received at least 7 days or 3 half-lives, whichever is longer, prior to the start date for protocol therapy.
- Other immunotherapy (ex: tumor vaccine): Patient is eligible after 42 days of completion. Steroids are excluded from inclusion in immunotherapy.
- Radiation Therapy: Patients must not have received radiation for a minimum of two weeks prior to first dose of the drug for small port. If extensive bone marrow radiation, at least 42 days must have elapsed.
- Palliative radiotherapy on study is permitted for the treatment of painful bony lesions providing the lesions were known at the time of study entry and the Investigator clearly indicates that the need for palliative...
- Hematopoietic Stem Cell Transplant (HSCT): Patients are eligible 12 weeks after date of autologous hematopoietic stem cell infusion following myeloablative therapy (timed from first day of this protocol therapy)...
- \^131 I-MIBG therapy: A minimum of 6 weeks must have elapsed after \^131 I-MIBG therapy prior to start of protocol therapy.
- Growth factors: Patients are eligible 14 days after last dose of long-acting growth factor (ex: peg-GCSF) or 7 days after short acting growth factor.
- Any investigational agent or anticancer therapy other than chemotherapy and not otherwise noted: Not within 2 weeks prior to planned start of TPX-0005 (Repotrectinib) or 5 half-lives, whichever is shorter. Full recovery...
- Any prior treatment with a tyrosine kinase inhibitor (TKI) of ALK/ROS/NTRK does NOT exclude patient from study (Patients are eligible for study at least 7 days or 5 half-lives, whichever is shorter, after last dose)
- Disease Status
- Patients must have relapsed or refractory disease despite standard therapy.
- Phase 1: Patients must have evaluable or measurable disease
- Phase 2: All patients must have measurable disease (per Appendices 1-3) at time of enrollment
- Exception: Patients with DIPG must have recurrent and/or progressive disease after upfront radiation therapy. Any number of prior recurrences is permitted.
- Biopsy Requirement °Archived tissue must be available for analysis, but no fresh biopsy is required (exception: patients with DIPG do not require archived tissue). If no archival tissue is available, waiver may be...
- Patients with Primary CNS Tumors:
- Patients with primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 14 days prior to enrollment
- Archived tissue and histologic verification requirement are waived for patients with diffuse intrinsic pontine glioma (DIPG)
- Performance Score: Patients must have a Lansky (\< 16 years age) or Karnofsky (≥ 16 years age) score of at least 50. Patients who are unable to walk because of paralysis or tumor pain, but who are up in a wheelchair...
- No bone marrow involvement
- Absolute Neutrophil Count ≥1000/mm\^3 (1 x 10\^9/L)
- Platelet Count ≥100,000/mm \^3 (100 x 10\^9/L); transfusions allowed
- Hemoglobin ≥ 8.0 g/dL, transfusions are allowed
- Known bone marrow involvement (applicable for phase 2 only)
- Absolute Neutrophil Count ≥750/mm 3 (0.75 x 10\^9/L)
- Platelet Count ≥50,000/mm\^3 (100 x 10\^9/L), transfusions allowed
- Hemoglobin ≥ 8.0 g/dL, transfusions are allowed
- Serum Creatinine or Creatinine Clearance\ Creatinine within normal limits for age/gender (see table below) or creatinine clearance or nuclear GFR ≥ 60 mL/min/1.73m\^2
- Total Serum Bilirubin \<2.5 x ULN for age/gender
- Liver Transaminases (AST/ALT) \<2.5 x ULN for age/gender; \< 5 x ULN for age/gender if liver metastasis is present
- Serum calcium, magnesium and potassium Normal for age/gender or ≤ CTCAE Grade 1 with or without supplementation.
- Cardiac Function Echocardiogram with left ventricular shortening fraction \>25% and QTc Friderica (QTcF) \</= 470ms on screening electrocardiogram
- AST/ALT = aspartate aminotransferase/alanine aminotransferase, ULN = upper limit of normal
- Adequate Renal Function using the Schwartz formula for estimating GFR Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
- Females of Childbearing potential: Must have negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation. Females of childbearing potential...
- Ability to comply with outpatient visits, laboratory testing, and study procedures during study participation
- The patient, parent or guardian must voluntarily sign and date an informed consent approved (in addition to pediatric assent, if required) by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior...
- Age:
- Phase 1 (Part A): ≤ 30 years old (age at C1D1)
- Phase 1 (Part B): \< 12 years old (age at C1D1)
- Phase 2: ≤ 30 years old (age at C1D1)
- Disease:
- Phase 1: Pediatric patients with relapsed/refractory solid tumors (including primary CNS tumors). Patients with ALK, ROS1, or NTRK1/2/3 fusions are permitted to enroll in this cohort if progressed on prior targeted...
- Phase 2
- Cohort 1: Patients with molecularly defined desmoplastic small round cell tumor (DSRCT)
- Cohort 2: Exploratory cohort of patients with relapsed or refractory solid tumors including CNS tumors (no requirement of ALK, ROS1, NTRK1-3 aberrations). Patients with ALK, ROS1, or NTRK1/2/3 fusions are permitted to...
- Cohort 3: Patients with recurrent or progressive DIPG. Patients with typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons on at least 1 axial T2-weighted image...
- Patients treated in Phase 1 at RP2D will be evaluable in the Phase 2 cohort if they meet all other for the specified cohort. Patients receiving oral capsule OR oral suspension can be included in Phase 2 cohort...
- Tissue Analysis
- Phase 1: All patients must have archived tissue available for analysis (exception: DIPG patients), but ALK/ROS/NTRK status verification is not required prior to enrollment. If no archival tissue is available, waiver may...
- Phase 2: Prior to enrollment, all patients must have ALK/ROS/NTRK status evaluated in CLIA lab or equivalent by any nucleic acid-based diagnostic testing method (e.g., next-generation sequencing [NGS], Sanger...
What rules you out
- Phase 1- patients with known bone marrow disease
- Concurrent participation in another therapeutic clinical trial
- Major surgery within 14 days (2 weeks) prior to C1D1. Central venous access (Broviac, MediPort) placement does not meet criteria for major surgery.
- Pregnancy or lactation
- Known active systemic infections requiring ongoing treatment (bacterial, fungal, viral including human immunodeficiency virus positivity). Skin or other superficial infections requiring topical treatment only are not an...
- Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
- Peripheral neuropathy CTCAE grade ≥ 3.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or that may interfere with the...
- Current use or anticipated need for drugs that are known to be strong CYP3A4 inhibitors or inducers
- Disease progression while on treatment with irinotecan/temozolomide.
- Gilbert Syndrome or Crigler-Najjar
- Prolonged QTc: 450m/s for male patients and 470ms for female patients.
The study team makes the final eligibility decision.
Where it's taking place
- New York, New York, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 1 year to 25 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include New York, New York, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.