Lorlatinib + Standard Therapy for Neuroblastoma

Recruiting at 167 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Disqualifiers: Pregnancy, Bone marrow failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

750 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining lorlatinib (Lorbrena) with standard therapy or using a radioactive drug like iobenguane I-131 can more effectively treat neuroblastoma or ganglioneuroblastoma in younger patients. The researchers aim to determine if these approaches can target and halt tumor cell growth more effectively than standard therapy alone. It suits patients newly diagnosed with high-risk neuroblastoma or ganglioneuroblastoma who have not undergone extensive prior treatment. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both iobenguane I-131 and lorlatinib are safe treatments. Studies found iobenguane I-131 to be safe and well-tolerated in patients with certain cancers, such as neuroblastoma, without major severe side effects.

Regarding lorlatinib, earlier research indicates it is safe for children, even when combined with chemotherapy. No serious lung-related side effects were reported, which can sometimes occur with similar treatments. Both treatments have shown promise in treating high-risk neuroblastoma, with safety data supporting their use in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for neuroblastoma because they bring innovative approaches to targeting cancer cells. Lorlatinib, one of the study treatments, is different from traditional chemotherapy because it specifically inhibits a protein called ALK, which is often mutated in neuroblastoma, potentially leading to more effective targeting of cancerous cells. Iobenguane I-131, another treatment in the study, is a radiopharmaceutical that uniquely delivers targeted radiation directly to tumor cells, sparing more of the surrounding healthy tissue compared to conventional radiation therapy. These cutting-edge treatments offer promising new avenues for tackling a challenging cancer, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for neuroblastoma?

Research has shown that iobenguane I-131, one of the treatments in this trial, can effectively treat high-risk neuroblastoma. In studies, patients experienced reductions in tumor size and markers after treatment. This drug delivers targeted radiation to tumor cells while protecting healthy cells.

Lorlatinib, another treatment option in this trial, has also shown promise, especially for certain types of neuroblastoma. Research found that it can reach the brain, improving responses there. In some cases, it provided lasting benefits, particularly in patients without specific genetic changes. Both treatments are being studied in separate arms of this trial for their potential to improve results when used with standard therapies. ^{2 4 6 7 8}

Who Is on the Research Team?

Steven G DuBois

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients up to 30 years old with high-risk neuroblastoma or ganglioneuroblastoma. They must have certain levels of kidney and liver function, no prior systemic therapy (with some exceptions), and can't be pregnant or breastfeeding. Patients need a confirmed diagnosis and meet specific criteria based on their disease stage and features.

Inclusion Criteria

My cancer is in an advanced stage with a specific genetic change.

I was diagnosed with a certain stage of cancer before it spread, and I haven't had chemotherapy.

I am a child aged 10 to less than 13 years with a specific health measure.

Exclusion Criteria

I have a condition where my bone marrow doesn't produce enough blood cells.

I cannot receive targeted radiopharmaceutical therapy due to my health conditions.

Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive cyclophosphamide, topotecan hydrochloride, and other chemotherapy agents as part of induction therapy

5 cycles (approximately 15 weeks)

Multiple visits for chemotherapy administration

Consolidation Therapy

Patients undergo high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT)

2 cycles (approximately 8 weeks)

Inpatient stay for HSCT

Post-Consolidation Therapy

Patients receive sargramostim, dinutuximab, isotretinoin, and possibly lorlatinib

6 cycles (approximately 6 months)

Regular visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Every 3 months for 18 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Iobenguane I-131
• Lorlatinib

Trial Overview The study tests adding iobenguane I-131 or lorlatinib to standard therapy in treating high-risk neuroblastoma. Iobenguane I-131 delivers radiation directly to cancer cells, while lorlatinib blocks enzymes that help tumor growth. The goal is to see if these additions improve treatment outcomes.

How Is the Trial Designed?

Group I: Arm E (lorlatinib, chemotherapy, HSCT, EBRT) Experimental Treatment 22 Interventions

See Arm E in detailed description.

Group II: Arm D (chemotherapy, HSCT, EBRT) Experimental Treatment 22 Interventions

See Arm D in detailed description.

Group III: Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT) Experimental Treatment 24 Interventions

See Arm C in detailed description. Closed to accrual as of 12/17/20.

Group IV: Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT) Experimental Treatment 24 Interventions

See Arm B in detailed description.

Group V: Arm A (chemotherapy, HSCT, EBRT) Experimental Treatment 22 Interventions

See Arm A in detailed description.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A phase 1 study demonstrated that lorlatinib is both safe and effective for children with treatment-refractory or relapsed ALK-driven neuroblastoma, highlighting its potential as a new treatment option.

These preliminary findings suggest that lorlatinib could provide hope for young patients who have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of lorlatinib against ALK-driven refractory or relapsed neuroblastoma. Suk, Y., Singh, SK.[2023]

In a pilot study involving 68 children with newly diagnosed high-risk neuroblastoma, 86.8% completed induction chemotherapy and received 131 I-MIBG therapy, demonstrating the treatment's feasibility.

The study found that while there were some severe side effects, including sinusoidal obstruction syndrome (SOS), the 15 mCi/kg dose of 131 I-MIBG showed a high feasibility rate of 96.7%, supporting further investigation in a larger randomized trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A safety and feasibility trial of 131 I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study. Weiss, BD., Yanik, G., Naranjo, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6478145/

Iodine‐131‐meta‐iodobenzylguanidine therapy for patients ... Patients with newly diagnosed high‐risk (HR) neuroblastoma (NBL) still have a poor outcome, despite multi‐modality intensive therapy.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00992173?tab=table

Efficacy and Safety of Ultratrace™ Iobenguane I 131 in ... Have high-risk neuroblastoma with relapsed/refractory disease at any time. MIBG avid disease demonstrated by 131I or 123I -MIBG uptake into tumor at ≥ one site ...

3. trial.medpath.com trial.medpath.com/clinical-trial/4789113888a9406c/nct00992173-phase-2b-study-ultracrace-iobenguane-neuroblastoma

Efficacy and Safety of Ultratrace™ Iobenguane I 131 in ... The primary purpose of the study is to determine if Ultratrace iobenguane I 131 can be used to successfully treat high-risk neuroblastoma. The study will also ...

4. ascopubs.org ascopubs.org/doi/10.1200/jco.2008.26.15_suppl.4605

A phase I study of Iobenguane I 131 to evaluate MTD ... Conclusions: Reductions in tumor volume, tumor dimension per RECIST, and tumor markers were observed in all 5 evaluable patients at 3 months ...

5. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/E7080-G000-230

A Study of Therapeutic Iobenguane (131-I) for Relapsed, ... The study will be conducted in male and female subjects, greater than 1 year of age, with iobenguane avid, relapsed, high-risk neuroblastoma.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.4_suppl.388

Pooled safety analysis of high-specific-activity I-131 MIBG ... Conclusions: HSA I-131 MIBG was safe and well-tolerated among subjects with iobenguane scan positive cancers. No trends were discerned between ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4385691/

Iodine-131 Metaiodobenzylguanidine Therapy for ... The 3-year EFS with or without I-131 MIBG therapy was 49% and 33%. The difference was not statistically significant; however these results might indicate the ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT240937

Pooled safety analysis of high-specific-activity I-131 MIBG ... Conclusions: HSA I-131 MIBG was safe and well-tolerated among subjects with iobenguane scan positive cancers. No trends were discerned between baseline ...