Authorised Phase I and Phase II (Integrated)- Other Advanced solid tumors

Phase 1/2 Open Label solid tumour Safety and Tolerability study in Pediatric and Young Adult subjects.

EU CTIS ID: 2023-506464-14-00

What this study is testing

Phase 2 Study Determine the antitumor activity of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring ROS1 or NTRK1-3 alterations.

  • Phase I and Phase II (Integrated)- Other

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • For Phase 2: EU will not enroll subjects in Cohort 1. Cohort 2: Subjects with NTRK+ advanced solid tumors (including primary CNS tumors), TRK TKI-pretreated. Nonresponse, disease progression or intolerability to at least 1 but no more than 2 prior TRK TKIs. Any prior lines are allowed. Subjects must have prospectively confirmed measurable disease by BICR prior to enrollment. Cohort 3: the EU: (1) will only enroll subjects with ROS1 gene fusions. •Documented genetic ROS1 or NTRK1-3 alteration as identified by local testing in a CLIA laboratory in the US or equivalent. •For subjects enrolled per tissue-based test, adequate tumor tissue should be sent prior to enrollment to the central lab. If archived tumor tissue is not available, a fresh biopsy should be obtained. For subjects enrolled by liquid biopsy test; blood samples should be sent prior to enrollment to the central lab.
  • Screening Local laboratory values: ANC≥1.5 × 109/L, ≥0.75 × 109L, if known bone marrow involvement PLT ≥100 × 109/L independent of platelets transfusion support for at least 7 days prior to dosing, ≥50 × 109/L, if known bone marrow involvement Hemoglobin≥ 8.0 g/dL independent of red blood cell transfusion support for at least 7 days prior to dosing, unless bone marrow involvement identified at enrollment Serum creatinine or creatinine clearance* Within normal limits per age or creatinine clearance or nuclear GFR>40 mL/min Total serum bilirubin < 1.5 × ULN AST/ALT<2.5 × ULN; <5 × ULN if liver metastases are present ALP <2.5 × ULN; <5 × ULN if liver and/or bone metastasis are present. Serum calcium, magnesium, and potassium: Normal or ≤CTCAE grade 1 with or without supplementation. •Serum Creatinine by Age Age < 6 years - Maximum Serum Creatinine (mg/dL) – Male: 0,8 - Female: 0,8 / Maximum Serum Creatinine (μmol/L) – Male: 71 Female: 71 Age 6 to < 10 years - Maximum Serum Creatinine (mg/dL) – Male: 1 - Female: 1 / Maximum Serum Creatinine (μmol/L) – Male: 88 - Female: 88 Age 10 to < 13 years - Maximum Serum Creatinine (mg/dL) – Male: 1.2 - Female: 1.2 / Maximum Serum Creatinine (μmol/L) – Male: 106 - Female: 106 Age 13 to < 16 years - Maximum Serum Creatinine (mg/dL) – Male: 1,5 - Female: 1,4 / Maximum Serum Creatinine (μmol/L) – Male: 132 - Female: 124 Age ≥ 16 years - Maximum Serum Creatinine (mg/dL) – Male: 1,7 - Female: 1,4 / Maximum Serum Creatinine (μmol/L) – Male: 150 - Female: 124
  • Reproductive Status: For female and male participants, see Protocol Section 5.1 for the full list of criteria.
  • The subject, parent or guardian must voluntarily sign and date an informed consent approved (in addition to pediatric assent, if required) by an IEC, prior to the initiation of any study specific procedures.
  • Age:  Phase 1: Age < 12 years (age at Cycle 1 Day 1)  Phase 2: Up to age 25 years (age at Cycle 1 Day 1). While the Phase 1 dose escalation is ongoing, subjects 12 years of age and above may be enrolled directly in the Phase 2 part of the study. Subjects age < 12 years of age will be enrolled in the Phase 2 part after determination of the pediatric RP2D in Phase 1.
  • Ability to comply with outpatient visits, laboratory testing, and study procedures during study participation.

You likely can't join if

  • Concurrent participation in another therapeutic clinical trial.
  • Subjects being treated with or anticipating the need for treatment with strong cytochrome P450 (CYP)3A4 inhibitors or inducers as listed in Appendix 4.
  • Any potential allergies to repotrectinib and/or its excipients
  • Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
  • Major surgery within 14 days (2 weeks) prior to Cycle 1 Day 1. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
  • Subjects who are pregnant or breast feeding.
See the full eligibility criteria
Who can join
  • For Phase 2: EU will not enroll subjects in Cohort 1. Cohort 2: Subjects with NTRK+ advanced solid tumors (including primary CNS tumors), TRK TKI-pretreated. Nonresponse, disease progression or intolerability to at least 1 but no more than 2 prior TRK TKIs. Any prior lines are allowed. Subjects must have prospectively confirmed measurable disease by BICR prior to enrollment. Cohort 3: the EU: (1) will only enroll subjects with ROS1 gene fusions. •Documented genetic ROS1 or NTRK1-3 alteration as identified by local testing in a CLIA laboratory in the US or equivalent. •For subjects enrolled per tissue-based test, adequate tumor tissue should be sent prior to enrollment to the central lab. If archived tumor tissue is not available, a fresh biopsy should be obtained. For subjects enrolled by liquid biopsy test; blood samples should be sent prior to enrollment to the central lab.
  • Screening Local laboratory values: ANC≥1.5 × 109/L, ≥0.75 × 109L, if known bone marrow involvement PLT ≥100 × 109/L independent of platelets transfusion support for at least 7 days prior to dosing, ≥50 × 109/L, if known bone marrow involvement Hemoglobin≥ 8.0 g/dL independent of red blood cell transfusion support for at least 7 days prior to dosing, unless bone marrow involvement identified at enrollment Serum creatinine or creatinine clearance* Within normal limits per age or creatinine clearance or nuclear GFR>40 mL/min Total serum bilirubin < 1.5 × ULN AST/ALT<2.5 × ULN; <5 × ULN if liver metastases are present ALP <2.5 × ULN; <5 × ULN if liver and/or bone metastasis are present. Serum calcium, magnesium, and potassium: Normal or ≤CTCAE grade 1 with or without supplementation. •Serum Creatinine by Age Age < 6 years - Maximum Serum Creatinine (mg/dL) – Male: 0,8 - Female: 0,8 / Maximum Serum Creatinine (μmol/L) – Male: 71 Female: 71 Age 6 to < 10 years - Maximum Serum Creatinine (mg/dL) – Male: 1 - Female: 1 / Maximum Serum Creatinine (μmol/L) – Male: 88 - Female: 88 Age 10 to < 13 years - Maximum Serum Creatinine (mg/dL) – Male: 1.2 - Female: 1.2 / Maximum Serum Creatinine (μmol/L) – Male: 106 - Female: 106 Age 13 to < 16 years - Maximum Serum Creatinine (mg/dL) – Male: 1,5 - Female: 1,4 / Maximum Serum Creatinine (μmol/L) – Male: 132 - Female: 124 Age ≥ 16 years - Maximum Serum Creatinine (mg/dL) – Male: 1,7 - Female: 1,4 / Maximum Serum Creatinine (μmol/L) – Male: 150 - Female: 124
  • Reproductive Status: For female and male participants, see Protocol Section 5.1 for the full list of criteria.
  • The subject, parent or guardian must voluntarily sign and date an informed consent approved (in addition to pediatric assent, if required) by an IEC, prior to the initiation of any study specific procedures.
  • Age:  Phase 1: Age < 12 years (age at Cycle 1 Day 1)  Phase 2: Up to age 25 years (age at Cycle 1 Day 1). While the Phase 1 dose escalation is ongoing, subjects 12 years of age and above may be enrolled directly in the Phase 2 part of the study. Subjects age < 12 years of age will be enrolled in the Phase 2 part after determination of the pediatric RP2D in Phase 1.
  • Ability to comply with outpatient visits, laboratory testing, and study procedures during study participation.
  • Subjects must have recovered from the acute toxic effects of all previous therapies prior to study enrollment to CTCAE v4.03 criteria ≤ grade 1, with the exception of alopecia. Subjects must not have received the therapies indicated below for the specified time period: •Chemotherapy: Last dose given at least 14 days or 5 half-lives (whichever is shorter) before the start date for repotrectinib. •Monoclonal antibodies (not including IO therapeutic antibodies): Last dose given at least 21 days prior to the start date for repotrectinib. •Immunotherapy (eg, IO therapeutic antibodies or tumor vaccine): Subject is eligible after 28 days of completion prior to first dose of repotrectinib. Steroids are not considered immunotherapy. •Radiation therapy: Subjects must not have received radiation for a minimum of 2 weeks prior to study enrollment. If extensive bone marrow radiation, at least 42 days must have elapsed. •HSCT: Subjects are eligible 12 weeks after infusion following myeloablative therapy (timed from first day of repotrectinib). Subjects who have received an infusion to support nonmyeloablative therapy (such as 131I MIBG) are eligible at any time as long as they meet the other criteria. •131I-MIBG therapy: A minimum of 6 weeks must have elapsed after 131I-MIBG therapy prior to start of repotrectinib. •Growth factors: Subjects are eligible 14 days after last dose of longacting growth factor or 7 days after short-acting growth factor. •Any investigational agent or anticancer therapy other than chemotherapy and not otherwise noted: At least 14 days or 5 half-lives (whichever is shorter) must have elapsed prior to the planned start of repotrectinib treatment. •Any prior treatment with a TKI of ROS1 or NTRK does NOT exclude subject from study.
  • All subjects must have measurable disease by RECIST v1.1 or RANO criteria at time of enrollment. For Phase 2 subjects in Cohort 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. •Exception: Neuroblastoma subjects are permitted to have evaluable disease only.
  • Subjects with Primary CNS Tumors or metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
  • Subjects must have a Lansky (<16 years) or Karnofsky (≥16 years) score ≥50. Subjects who are unable to walk because of paralysis or tumor pain, but who are upright in a wheelchair, will be considered ambulatory for the performance status.
  • Life expectancy ≥12 weeks.
What rules you out
  • Concurrent participation in another therapeutic clinical trial.
  • Subjects being treated with or anticipating the need for treatment with strong cytochrome P450 (CYP)3A4 inhibitors or inducers as listed in Appendix 4.
  • Any potential allergies to repotrectinib and/or its excipients
  • Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
  • Major surgery within 14 days (2 weeks) prior to Cycle 1 Day 1. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
  • Subjects who are pregnant or breast feeding.
  • Subjects with known active infections requiring ongoing treatment (bacterial, fungal, or viral, including HIV).
  • Subjects with gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
  • Any of the following cardiac criteria: • Mean resting corrected QT interval (electrocardiogram [ECG] interval measured from the onset of the QRS complex to the end of the T wave) for heart rate > 480 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec) • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval (Appendix 5)
  • Subjects with peripheral neuropathy with CTCAE grade ≥ 2.
  • Subjects with other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that, per the judgement of the Investigator or Sponsor, may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of study results, or make the subject inappropriate for entry into the study, or could compromise protocol objectives.

The study team makes the final eligibility decision.

Where it's taking place

  • Taiwan
  • Singapore
  • United States
  • Korea, Republic of
  • Canada
  • Australia

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, 0-17 years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Taiwan; Singapore; United States; Korea, Republic of; Canada; Australia. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.