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NCT03107988 · CITED IN SOURCE DOCUMENTS

NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE1
Status at capture
COMPLETED
Registry last update
2025-09-15

Lorlatinib is a novel inhibitor across ALK variants, including those resistant to crizotinib. In this first pediatric phase 1 trial of lorlatinib, the drug will be utilized as a single agent and in combination with chemotherapy in patients with relapsed/refractory neuroblastoma. The dose escalation phase of this study (Cohort A1) uses a traditional Phase I 3+3 design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 6 patients (Cohort B1), within which ALKi naïve patients will be prioritized, will be initiated. Parallel cohorts will be initiated in adults or patients with large BSA (Cohort A2) and in combination with chemotherapy upon establishing RP2D (Cohort B2).

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

MTD/RP2D Determination A1

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outcome · POSTED

MTD/RP2D Determination A2

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outcome · POSTED

MTD/RP2D Determination B2

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outcome · POSTED

Describe Non-Hematological Toxicities (A1 and B1)

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outcome · POSTED

Describe Hematological Toxicities (A1 and B1)

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outcome · POSTED

Describe Non-Hematological Toxicities (A2)

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outcome · POSTED

Describe Hematological Toxicities (A2)

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outcome · POSTED

Describe Non-Hematological Toxicities (B2)

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outcome · POSTED

Describe Hematological Toxicities (B2)

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outcome · POSTED

Pharmacokinetics A1 and B1-Steady State AUC

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outcome · POSTED

Pharmacokinetics A2-Steady State AUC

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outcome · POSTED

Pharmacokinetics B2-Steady State AUC

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outcome · POSTED

Overall Response A1 and B1

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outcome · POSTED

Overall Response A2

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outcome · POSTED

Overall Response B2

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outcome · POSTED

Pharmacokinetics A1 and B1-Cmax

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outcome · POSTED

Pharmacokinetics A2-Cmax

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outcome · POSTED

Pharmacokinetics B2-Cmax

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: 1\) Patients are required to have an activating ALK aberration in their tumor detected by certified assay (i.e. CLIA in the US.) prior to registration. The report from this test is required to be submitted for eligibility. Patients with at least one of the following genetic features in their tumor will be considered to have an activating ALK aberration: 1\. An ALK activating mutation; 2. ALK amplification (\> 10 signals of the ALK gene); 3. Presence of any ALK fusion protein that arises from a chromosomal translocation 2) Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines. 3\) Patients must have a history of high-risk neuroblastoma according to COG risk classification at the time of study registration. Patients who were initially considered low or intermediate-risk, but then reclassified as high-risk are also eligible. 4\) All patients must have at least one of the following a) Recurrent/progressive disease: after the diagnosis of high risk neuroblastoma at any time prior to enrollment regardless of response to frontline therapy b) No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma b1) Refractory disease- a best overall response of no response/stable disease since diagnosis of high risk neuroblastoma and at least 4 cycles of induction therapy. No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma. b2) Persistent disease- a best overall response of no partial response since diagnosis of high risk neuroblastoma and at least 4 cycles of induction therapy. No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma. 5\) Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below): 1. For recurrent/progressive or refractory disease, at least one MIBG avid bone site. 2. For persistent disease, if a patient has 3 or more MIBG avid lesions, then no biopsy is required. If a patients has only 1 or 2 MIBG avid bone lesion sites then biopsy confirmation of neuroblastoma or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment is required to be obtained at any time point prior to enrollment. 3. For MIBG non-avid tumors, patients must have at least one FDG avid site and a biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma at any time prior to enrollment from at least one FDG-avid site. 6\) Any amount of neuroblastoma tumor cells in the bone marrow done at the time of study enrollment based on routine morphology with or without immunocytochemistry in at least one sample from bilateral aspirates and biopsies. 7\) At least one soft tissue lesion that meets criteria for a TARGET lesion as defined by: <!-- --> 1. SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm, or for lymph nodes ≥ 15 mm on short axis. Lesions meeting size criteria will be considered measurable. 2. In addition to size, a lesion needs to meet one of the following criteria except for patients with parenchymal CNS lesions which only need to meet size criteria: b1) MIBG avid. For patients with recurrent/progressive or refractory disease, no biopsy is required. For patients with persistent disease only: If a patient has only 1 or 2 MIBG avid lesions sites, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at time of enrollment is required to be obtained. If a patient has 3 or more MIBG avid lesions, then no biopsy is required. b2) MIBG non avid tumors: Patients must have at least one FDG avid site and biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one FDG-PET avid site present at the time of enrollment. 8\) At least one non-target soft tissue lesion that is not measurable, but had a biopsy positive for neuroblastoma and/or ganglioneuroblastoma or is MIBG avid at any time prior to enrollment. 9\) Patients must have a life expectancy of at least 12 weeks and a Lansky (≤16 years) or Karnofsky (\>16 years) score of at least 50. 10\) Prior Therapy 1. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study registration. 2. Patients must not have received the therapies indicated below after disease evaluation or within the specified time period prior to registration on this study as follows: 1\. Myelosuppressive chemotherapy: must not have received within 2 weeks prior to registration. 2\. Biologic anti-neoplastics- agents not known to be associated with reduced platelet or ANC counts (including retinoids): must not have received within 7 days prior to registration. 3\. Monoclonal antibodies: must have received last dose at least 7 days or 3 half-lives whichever is longer, but no longer than 30 days (with recovery of any associated toxicities), prior to protocol therapy. 4\. Cellular Therapy (e.g. modified T cells, NK cells, dentritic cells etc.): must not have received within 3 weeks and resolution of all toxicities. 5\. Radiation: must not have received small port radiation within 7 days prior to registration. 6\. Hematopoietic Stem Cell Transplant: 7. IVIG 11) All patients must have adequate organ function defined as: \- Hematological Function: 1\. Absolute Phagocyte count (APC= neutrophils and monocytes): ≥ 1000/µL 2\. Absolute Neutrophil count: ≥750/µL 3\. Absolute Lymphocyte count ≥ 500/µL 4\. Platelet count: ≥ 50,000/µL (A1, A2, and B1); ≥ 75,000/µL (B2), transfusion independent (no platelet transfusions within 1 week) 5\. Hemoglobin ≥ 10 g/dL (may transfuse) 6\. Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria above. \- Renal Function: Age-adjusted serum creatinine ≤ to 1.5 x normal for age/gender OR creatinine clearance or GFR greater than or equal to 60 cc/min/1.73m2 \- Liver Function: Total bilirubin ≤ 1.5 x normal for age, AND SGPT (ALT) 135 and SGOT (AST) ≤ 3 x upper limit of normal. Sinusoidal obstruction syndrome (SOS) if present, must be stable or improving clinically \- Cardiac Function: Normal ejection fraction documented by either echocardiogram or radionuclide MUGA evaluation OR Normal fractional shortening documented by echocardiogram \- Pulmonary Function: No dyspnea at rest, no oxygen requirement. * Neuropsychological Function: Patients must exhibit ≤ grade 1 as defined by CTCAE V4 of nervous system disorders and psychiatric disorders 12) Reproductive Status: All post-menarchal females must have a negative beta-HCG. Males and females of reproductive age and childbearing potential must use effective contraception for the duration of their participation. 13\) Patients with other ongoing serious medical issues must be approved by the study chair prior to registration. 14\) Prior ALK inhibitor treatment- patients must not have been previously treated with lorlatinib. Prior therapy with other ALK inhibitors is allowed. 15\) Concomitant Therapy Restrictions: 1. Patients may not receive any other anti-cancer agents or radiotherapy while on protocol therapy. 2. Patient must not be receiving chronic systemic corticosteroids at doses greater than physiologic dosing (inhaled corticosteroids acceptable) 3. CYP34A inhibitors 4. CYP34A inducers 5. CYP34A substrates Exclusion Criteria: \- Pregnancy, breast feeding, or unwillingness to use effective contraception during the study. * Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. * Patients with disease of any major organ system that would compromise their ability to withstand therapy. * Patients who have received prior allogeneic stem cell transplant * Patients who are on hemodialysis. * Patients with an active or uncontrolled infection. * Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. * Patient with known history of acute or chronic severe psychiatric disorders * Patient with current history of suicidal ideation and history of suicide attempt in their lifetime * Patient declines participation in NANT 2004-05, the NANT Biology Study
healthy Volunteers
false
maximum Age
99 Years
minimum Age
1 Year
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    label
    Cohort A1 DL1
    type
    EXPERIMENTAL
  2. description
    Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    label
    Cohort A2 DL 3A
    type
    EXPERIMENTAL
  3. description
    Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    2. Drug: Cyclophosphamide
    3. Drug: Topotecan
    4. Drug: Filgrastim/pegfilgrastim
    label
    Cohort B2 DL4B
    type
    EXPERIMENTAL
  4. description
    Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    label
    Cohort A1 DL2
    type
    EXPERIMENTAL
  5. description
    Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    label
    Cohort A1 DL3
    type
    EXPERIMENTAL
  6. description
    Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    label
    Cohort A1 DL4
    type
    EXPERIMENTAL
  7. description
    Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    label
    Cohort A1 DL5
    type
    EXPERIMENTAL
  8. description
    Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    label
    Cohort A2 DL4A
    type
    EXPERIMENTAL
  9. description
    Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    2. Drug: Cyclophosphamide
    3. Drug: Topotecan
    4. Drug: Filgrastim/pegfilgrastim
    label
    Cohort B2 DL5B
    type
    EXPERIMENTAL
  10. description
    Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    2. Drug: Cyclophosphamide
    3. Drug: Topotecan
    4. Drug: Filgrastim/pegfilgrastim
    label
    Cohort B2 DL3A
    type
    EXPERIMENTAL
  11. description
    Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    2. Drug: Cyclophosphamide
    3. Drug: Topotecan
    4. Drug: Filgrastim/pegfilgrastim
    label
    Cohort B2 DL4A
    type
    EXPERIMENTAL
  12. description
    Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
    intervention Names
    1. Drug: Lorlatinib
    label
    Cohort B1 DL5
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Cohort A1 DL1
    2. Cohort A1 DL2
    3. Cohort A1 DL3
    4. Cohort A1 DL4
    5. Cohort A1 DL5
    6. Cohort A2 DL 3A
    7. Cohort A2 DL4A
    8. Cohort A2 DL4A Expansion
    9. Cohort B1 DL5
    10. Cohort B2 DL3A
    11. Cohort B2 DL4A
    12. Cohort B2 DL4B
    description
    Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
    name
    Lorlatinib
    other Names
    1. PF06463922
    type
    DRUG
  2. arm Group Labels
    1. Cohort B2 DL3A
    2. Cohort B2 DL4A
    3. Cohort B2 DL4B
    4. Cohort B2 DL5B
    description
    Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
    name
    Cyclophosphamide
    other Names
    1. Cytoxan
    type
    DRUG
  3. arm Group Labels
    1. Cohort B2 DL3A
    2. Cohort B2 DL4A
    3. Cohort B2 DL4B
    4. Cohort B2 DL5B
    description
    Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
    name
    Topotecan
    other Names
    1. SKF-104864,Hycamtin®
    type
    DRUG
  4. arm Group Labels
    1. Cohort B2 DL3A
    2. Cohort B2 DL4A
    3. Cohort B2 DL4B
    4. Cohort B2 DL5B
    description
    Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC \> 2000/mm\^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy. Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
    name
    Filgrastim/pegfilgrastim
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
65
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Proportion of patients with course 1 DLT and/or course 2 neuropsychological DLT in cohort A1
    measure
    MTD/RP2D Determination A1
    time Frame
    All toxicities from enrollment until completion of course 2 (Day 56)
  2. description
    Proportion of patients with course 1 DLT and/or course 2 neuropsychological DLT in cohort A2
    measure
    MTD/RP2D Determination A2
    time Frame
    All toxicities from enrollment until completion of course 2 (Day 56)
  3. description
    Proportion of patients with course 1 DLT in cohort B2
    measure
    MTD/RP2D Determination B2
    time Frame
    All toxicities from enrollment until completion of course 1 (Day 28)
  4. description
    Proportion of patients with any grade 3 or greater non-hematological toxicities on any course in A1 and B1
    measure
    Describe Non-Hematological Toxicities (A1 and B1)
    time Frame
    All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
  5. description
    Proportion of patients with any grade 3 or greater hematological toxicities on any course in A1 and B1
    measure
    Describe Hematological Toxicities (A1 and B1)
    time Frame
    All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
  6. description
    Proportion of patients with any grade 3 or greater non-hematological toxicities in A2
    measure
    Describe Non-Hematological Toxicities (A2)
    time Frame
    All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
  7. description
    Proportion of patients with any grade 3 or greater hematological toxicities in A2
    measure
    Describe Hematological Toxicities (A2)
    time Frame
    All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
  8. description
    Proportion of patients with any grade 3 or greater non-hematological toxicities in B2
    measure
    Describe Non-Hematological Toxicities (B2)
    time Frame
    All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
  9. description
    Proportion of patients with any grade 3 or greater hematological toxicities in B2
    measure
    Describe Hematological Toxicities (B2)
    time Frame
    All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
secondary Outcomes
  1. description
    Steady State AUC for lorlatinib in patients in cohort A1 and B1
    measure
    Pharmacokinetics A1 and B1-Steady State AUC
    time Frame
    Day 1 through Day 15 (0, 1, 2, 24, 360, 361, 362, 364, 366 hours post-initial dose)
  2. description
    Steady State AUC for lorlatinib in patients in cohort A2
    measure
    Pharmacokinetics A2-Steady State AUC
    time Frame
    Day 1 through Day 15 (0, 1, 2, 24, 360, 361, 362, 364, 366 hours post-initial dose)
  3. description
    Steady State AUC for lorlatinib in patients in cohort B2
    measure
    Pharmacokinetics B2-Steady State AUC
    time Frame
    Day 1 through Day 15 (0, 1, 2, 24, 360, 361, 362, 364, 366 hours post-initial dose)
  4. description
    Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in cohort A1 and B1
    measure
    Overall Response A1 and B1
    time Frame
    From Day 1 of protocol therapy through 30 days following end of protocol therapy, an average of 10 months
  5. description
    Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in cohort A2
    measure
    Overall Response A2
    time Frame
    From Day 1 of protocol therapy through 30 days following end of protocol therapy, an average of 10 months
  6. description
    Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in cohort B2
    measure
    Overall Response B2
    time Frame
    From Day 1 of protocol therapy through 30 days following end of protocol therapy, an average of 10 months
  7. description
    Cmax for lorlatinib in patients in cohort A1 and B1
    measure
    Pharmacokinetics A1 and B1-Cmax
    time Frame
    Day 15
  8. description
    Cmax for lorlatinib in patients in cohort A2
    measure
    Pharmacokinetics A2-Cmax
    time Frame
    Day 15
  9. description
    Cmax for lorlatinib in patients in cohort B2
    measure
    Pharmacokinetics B2-Cmax
    time Frame
    Day 15
Full study description
brief Summary
Lorlatinib is a novel inhibitor across ALK variants, including those resistant to crizotinib. In this first pediatric phase 1 trial of lorlatinib, the drug will be utilized as a single agent and in combination with chemotherapy in patients with relapsed/refractory neuroblastoma. The dose escalation phase of this study (Cohort A1) uses a traditional Phase I 3+3 design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 6 patients (Cohort B1), within which ALKi naïve patients will be prioritized, will be initiated. Parallel cohorts will be initiated in adults or patients with large BSA (Cohort A2) and in combination with chemotherapy upon establishing RP2D (Cohort B2).
detailed Description
Lorlatinib is a novel inhibitor across ALK variants, including those resistant to crizotinib. An adult phase 1 study established an RP2D of 100mg QD for lorlatinib. In this first pediatric phase 1 trial of lorlatinib, the drug will be utilized as a single agent and in combination with chemotherapy in patients with relapsed/refractory neuroblastoma. The dose escalation phase of this study (Cohort A1) uses a traditional Phase I 3+3 design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 6 patients (Cohort B1), within which ALKi naïve patients will be prioritized, will be initiated. Parallel cohorts will be initiated in adults or patients with large BSA (Cohort A2) and in combination with chemotherapy upon establishing RP2D (Cohort B2). Lorlatinib will be administered orally via tablets or via oral dispersion if patient is unable to swallow tablets whole All patients will participate in mandatory pharmacokinetic testing.
Source references
references
  1. citation
    Goldsmith KC, Park JR, Kayser K, Malvar J, Chi YY, Groshen SG, Villablanca JG, Krytska K, Lai LM, Acharya PT, Goodarzian F, Pawel B, Shimada H, Ghazarian S, States L, Marshall L, Chesler L, Granger M, Desai AV, Mody R, Morgenstern DA, Shusterman S, Macy ME, Pinto N, Schleiermacher G, Vo K, Thurm HC, Chen J, Liyanage M, Peltz G, Matthay KK, Berko ER, Maris JM, Marachelian A, Mosse YP. Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results. Nat Med. 2023 May;29(5):1092-1102. doi: 10.1038/s41591-023-02297-5. Epub 2023 Apr 3.
    pmid
    37012551
    type
    DERIVED
  2. citation
    Baranowska-Kortylewicz J, Kortylewicz ZP, McIntyre EM, Sharp JG, Coulter DW. Multifarious Functions of Butyrylcholinesterase in Neuroblastoma: Impact of BCHE Deletion on the Neuroblastoma Growth In Vitro and In Vivo. J Pediatr Hematol Oncol. 2022 Aug 1;44(6):293-304. doi: 10.1097/MPH.0000000000002285. Epub 2021 Sep 6.
    pmid
    34486544
    type
    DERIVED
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        inib (added to conventional therapy) are being tested in patients with recurrent <em class="gene-name">ALK</em>-altered neuroblastoma (<a href="/clinicaltrials/NCT03107988">NCT03107988</a>) and in patients with newly diagnosed high-risk neuroblastoma with activated <em class="gene-name">ALK</em> (COG <a href="/clinicaltrials/NCT0
        end
        253398
        exact text
        NCT03107988
        start
        253387
      2. context exact
        o conventional therapy) are being tested in patients with recurrent <em class="gene-name">ALK</em>-altered neuroblastoma (<a href="/clinicaltrials/NCT03107988">NCT03107988</a>) and in patients with newly diagnosed high-risk neuroblastoma with activated <em class="gene-name">ALK</em> (COG <a href="/clinicaltrials/NCT03126916">ANBL
        end
        253411
        exact text
        NCT03107988
        start
        253400
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/d023d406c02e860e22.html
      source file sha256
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      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:09.227808+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      5a0bcb41a33182c1bb316ea92b74ca10701add33aec3077a54a565e6d80cbf53
      source title
      Neuroblastoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 28, 2025
        datetime
        2025-04-28T12:00:00Z
        display
        April 28, 2025

    Preserved source evidence · Independent clinical review pending · Not medical advice