Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Patients will receive 12-week induction Lorlatinib followed by radical surgery or local radiotherapy or continue Lorlatinib through MDT and optional consolidation lorlatinib for up to 2 years.

Patients were assigned to receive oral lorlatinib at a dose of 100 mg daily in a course of treatment that was measured in cycles of 28 days. 3 cycles of induction treatment will be required for the study.

Lorlatinib

Wen-Zhao Zhong, MD.

Chao Zhang, MD.

Ben-Yuan Jiang, MD.

A prospective, single-arm, open-label phase 2 study that evaluates the efficacy and safety of induction Lorlatinib in stage III non-small cell lung cancer and explores the clinical feasibility of dynamic ctDNA and multidisciplinary assessment in guiding local treatments.

Simon two-stage was applied to estimate the required sample size for the study. Overall an estimated 43 patients were required and at least 12 patients achieved pathological complete response would be deemed as positive result. Patients will be provided 3 cycles induction Lorlatinib 100mg and then assessed whether patients would be eligible for radical surgery or local radiotherapy through multidisciplinary evaluation. After local intervention, patients could choose consolidation treatment of Lorlatinib for up to 2 years or adjuvant doublet chemotherapy for up to 4 cycles. Dynamic blood samples will be collected before and after induction Lorlatinib as well as consolidation treatment. The primary endpoints is pCR for patients who received radical surgery.

A Simon two-stage design was applied. Primary endpoint for this study was pCR. The unacceptable response rate for pCR was less than 20% and desirable response rate was 40%. The error rate for alpha was set as 0.05 and 0.2 for beta. The Optimal assay was chosen and 43 patients were to be enrolled to meet adequate statical power. 13 patients would be enrolled in stage I and at least 3 patients achieved pCR were required to proceed stage II enrollment. Overall, if 12 patients achieved pCR, the study would be determined as positive. 10% drop-off rate should be considered and at least 48 patients should be enrolled.

Induction Lorlatinib in Stage III Non-small Cell Lung Cancer

Induction Lorlatinib for ALK Fusion Locally Advanced Non-small Cell Lung Cancer: A Prospective, Single Arm, Open-label Phase 2 Study

Partial clinicopathological data of participants will be presented in the corresponding manuscript.

The pathological complete response is defined as the absence of residual tumor in both lung and regional lymph nodes after induction treatment and radical surgery.

The period after initiation of induction treatment till the time of disease progress or any cause of death.

ORR is the number of participants with a Complete Response (CR) and Partial Response (PR) divided by the total number of enrolled participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared to baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions.

The period after radical surgery till the time of disease relapse with either local recurrence or distant metastasis.

The exploratory ctDNA alteration will be stratified into three parts. 1) Induction period: overall ctDNA clearance rate (before and after induction treatment); 2) Posttreatment period: ctDNA clearance rate after local treatment; 3) Consolidation period: 1-year and 2-year ctDNA positive rate during consolidation treatment.

OS was assessed from initiation of treatment to death as a result of any cause.

Incidence of AE/SAE which has been confirmed correlation with Lorlatinib or local treatment.

Guangdong Provincial People's Hospital

Head of Pulmonary Surgery

Nervous System Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Glioma

Diffuse Intrinsic Pontine Glioma

Glioblastoma

Astrocytoma

Lymphoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Brain Stem Neoplasms

Infratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Lymphosarcoma

Anaplastic Astrocytoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Amino Acids

Carboplatin

Cyclophosphamide

Methotrexate

Vincristine

Cisplatin

Tyrosine

Lorlatinib administered as monotherapy by PO (per os) or NG (nasogastric) for two 28-day cycles at 115 mg/m2/day (or maximum 200mg/dose), after which disease evaluation by Magnetic Resonance Imaging (MRI) imaging will be performed.

Lorlatinib monotherapy x2 cycles followed by maintenance therapy with lorlatinib (115 mg/m2/day) and BABY-POG chemotherapy backbone (vincristine, cyclophosphamide, cisplatin) The BABYPOG chemotherapy backbone regimen will consist of six 12-week courses. Each course will consist of cycles A, A2 and B, which will be administered consecutively, in 28-day cycles for a total of 72 weeks

Lorlatinib monotherapy x2 cycles followed by maintenance therapy with lorlatinib (115 mg/m2/day) and HIT-SKK chemotherapy backbone (cyclophosphamide, vincristine, methotrexate, carboplatin, etposide) The recommended HIT-SKK chemotherapy backbone regimen consists of modular chemotherapy cycles, three courses of 4 blocks each (Element IIS, Element IIIS/1, Element IIIS/2, and Element IVS). Each element will be administered consecutively at 2-3-week intervals. Elements IIS and IVS cycles will be repeated twice thereafter. The entire length of treatment for HIT-SKK will be approximately 42 weeks.

Lorlatinib monotherapy x2 cycles followed by Radiation Therapy and continue lorlatnib maintenance monotherapy (115 mg/m2/day) 28 days post completion of RT for 12 cycles

Continue maintenance monotherapy for total 12 cycles

Continue lorlatinib with BABY-POG chemotherapy backbone for 72 weeks

Lorlatinib with chemotherapy1

Continue lorlatinib with HIT-SKK chemotherapy backbone for 42 weeks

Lorlatinib with chemotherapy 2

Continue lorlatinib monotherapy 28 days post completion of radiation therapy for 12 cycles

Lorlatinib post Radiation

Leonie Mikael, PhD

Kathleen Dorris, MD

Eugene Hwang

Ashley Plant, MD

Susan Chi

David Ashley, MD

Peter de Blank, MD

Maryam Fouladi, MD, MSc

Michael J Fisher, MD

Patricia Baxter, MD

Sarah Leary

David Ziegler, MD

Tim Hassall, MD

Nicholas G Gottardo, MBChB

Eric Bouffet

Genevieve Legault, MD

Olaf Witt, MD

Jasper van der Lugt

Hamza Gorsi, MD

Susan Chi, MD

Maryam Fouladi, MD

The goal of this study is to determine the response of the study drug loratinib in treating children who are newly diagnosed high-grade glioma with a fusion in ALK or ROS1. It will also evaluate the safety of lorlatinib when given with chemotherapy or after radiation therapy.

This is a multi-institutional clinical trial of lorlatinib in children newly diagnosed with High Grade Glioma (HGG) harboring ROS1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) or ALK (anaplastic lymphoma kinase) fusions. In this pilot study, investigators will assess the disease control rate (Continued Complete Response (CCR), Complete Response (CR), Partial Response (PR), and Stable Disease (SD)) of lorlatinib, and feasibility and safety of lorlatinib administration in combination with standard chemotherapy in children with newly diagnosed HGG with ROS or ALK fusions who receive 2 cycles of lorlatinib administered orally, once daily, at 115 mg/m2/day (or maximum of 200mg/dose) continuously. Secondary objectives include overall survival (OS) and progression free survival (PFS) lorlatinib as a single agent and in combination with standard chemotherapy used in children ≤ 48 months with HGG, or post focal radiotherapy in children \> 48 months of age. Children with HGG who have a CCR or CR after 2 cycles of therapy will continue to receive single agent lorlatinib for a total of 12xs 28-day cycles. Continuation of treatment beyond 12 cycles, and up to maximum 26 cycles, may be considered for patients on lorlatinib monotherapy if they are receiving clinical benefit from the study, at the discretion of the treating physician. Patients with PR or SD after 2 cycles of lorlatinib monotherapy will go on to receive lorlatinib either in combination with standard backbone chemotherapy (BABYPOG or HIT-SKK, investigator's choice) or post standard radiotherapy, based on the patient's age. Patients with PD after 2 cycles will be taken off protocol therapy.

Based on recent trials conducted in this patient population, investigators conservatively estimate that 1 child with newly diagnosed DIPG or HGG with either ROS1 or ALK fusion will be enrolled every 2 months on this study. Patients will start at the recommended phase 2 dose of 115 mg/m2/day, continuously for 28 days, and one dose de-de-escalations will be allowed. A maximum of 15 eligible patients will be enrolled, anticipated over 2.5 years.

Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion

A Pilot Study of Lorlatinib for Treatment of Children With Newly Diagnosed High-Grade Glioma With ROS-1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) or ALK (Anaplastic Lymphoma Kinase) Fusion

To assess the disease control rate (Complete Response \[CR\], Continued Complete Response \[CCR\], Partial Response \[PR\] and Stable Disease \[SD\]) of lorlatinib in young children with newly diagnosed high-grade glioma with ALK or ROS1 fusion after 2 cycles of lorlatinib monotherapy.

Assess and further characterize the safety and toxicity of lorlatinib in pediatric patients newly diagnosed with HGG with a fusion in ALK or ROS. This will be achieved by calculating the number of participants with, as well as frequency and severity of, lorlatinib-related Adverse Events as assessed by CTCAE v5.0

To assess the objective response rate (ORR) (Complete Response \[CR\] and Partial Response \[PR\]) of lorlatinib in children with newly diagnosed high-grade glioma with ALK or ROS1 fusion after 2 cycles of lorlatinib monotherapy.

To assess overall (OS) of children with high-grade gliomas treated with a lorlatinib-containing regimen at 1, 3 and 5 years and compare it to historical data from BABYPOG and HIT-SKK.

To assess progression-free survival (PFS) of children with high-grade gliomas treated with a lorlatinib-containing regimen at 1, 3 and 5 years and compare it to historical data from BABYPOG and HIT-SKK.

Pfizer

Nationwide Children's Hospital

After 7-day lead-in 90mg/day, brigatinib 180mg/day from 4 to 10weeks(optimal duration: 6 weeks)

Brigatinib

Hye Ryun Kim

This study is single arm, open label, phase II trial for resectable ALK+ NSCLC. Eligible patients will receive brigatinib after 7-day lead-in 90mg from 4 to 10 weeks.

The objective of this study is as follows.

* Primary objective: To identify molecular mechanism of DTP causing innate drug resistance to neoadjuvant brigatinib in resectable NSCLC harboring ALK fusion by analyzing single cell RNA-seq.
* Secondary objectives:

  1. To assess the pathologic response rate to neoadjuvant treatment with Brigatinib
  2. To evaluate the clinical efficacy in resectable ALK-positive NSCLC patients treated with brigatinib induction therapy
  3. To evaluate the successful curative resection rate
  4. To evaluate the safety of brigatinib as neoadjuvant treatment in resectable ALK-rearranged NSCLC patients.
  5. To investigate the changes of ALK rearrangement and other hot spot mutations by GUARDANT LUNAR assay of circulating tumor DNA present in blood plasma immediately with serial sampling.
  6. To assess of variant allele frequencies between pre-treatment and post-treatment sampling by GUARDANT LUNAR assay
  7. To explore cell-free biomarkers that may be predictive of response or primary resistance to brigatinib neoadjuvant therapy

This study is single arm, open label, phase II trial for resectable ALK+ NSCLC. Eligible patients will receive brigatinib after 7-day lead-in 90 mg from 4 to 10 weeks. The surgery with curative intent will be performed within 4 - 10 weeks after initiating brigatinib (optimal duration: 6 weeks). The surgery with curative intent represents more than sublobar resection with mediastinal lymph node dissection. Patients take it up to the day before surgery and can be allow stop up to 3 days before surgery by physician's discretion.

Post-operative adjuvant treatment will be conducted based on the treating physician's best medical judgement.

Brigatinib will be administered orally at a dose of 90 mg QD for the first 7 days. Patients who have tolerated the 90 mg starting dose on Days 1 through 7 will be expected to increase their dose to 180 mg QD beginning on Day 8 and continuously every day, with a 28-day study procedure execution cycle. The study drug shall be taken approximately at the same time of the day each day. It may be taken with or without food. Patients shall be instructed to swallow the tablets whole and not crush or chew them. Patients will take the dose with water (recommended 240 mL). If a dose of brigatinib is missed or vomiting occurs after taking a dose, do not administer an additional dose and take the next dose of brigatinib at the scheduled time.

The patient's daily dose of brigatinib should not be increased to 180 mg if any of the following adverse reactions are experienced during treatment at 90 mg QD:

* Interstitial lung disease (ILD)/pneumonitis (any grade).
* Symptomatic bradycardia (Grade 2 or greater).
* Grade 2 or higher visual disturbance.
* Any other Grade 3 or higher adverse reaction.

A Window of Opportunity Study for Investigating Drug Tolerant Persister (DTP) to Preoperative Brigatinib in Resectable Non-small Cell Lung Cancer (NSCLC) Harboring ALK Fusions.

Molecular candidates identified by analyzing scRNA-seq from pre-treatment tumor biopsy specimens and tumor tissue acquired at the time of surgical resection.

absence of (0%) viable tumor present histologically in the resected tumor specimen

≤10% residual viable tumor following neoadjuvant therapy

CR+PR rate based on RECIST ver 1.1 criteria.

It will be recorded as rate of patients initially assessed as surgically resectable, who are subsequently unable to undergo surgical resection due to either treatment-related adverse events (AEs) or disease progression

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Induction Lorlatinib in Stage III Non-small Cell Lung Cancer	NCT05740943	Stage III NSCLC Surgery	Lorlatinib	18 Years - 75 Years	Guangdong Provincial People's Hospital
Induction Lorlatinib in Stage III Non-small Cell Lung Cancer	NCT05740943	Stage III NSCLC Surgery	Lorlatinib	18 Years - 75 Years	Guangdong Provincial People's Hospital
Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion	NCT06333899	High Grade Glio... Diffuse Intrins... Anaplastic Astr... Infant Type Hem... Glioblastoma Glioblastoma Mu... WHO Grade III G... WHO Grade IV Gl... Diffuse Midline...	Lorlatinib Lorlatinib with... Lorlatinib with... Lorlatinib post...	1 Year - 21 Years	Nationwide Children's Hospital
A Window of Opportunity Study for Investigating Drug Tolerant Persister (DTP) to Preoperative Brigatinib in Resectable Non-small Cell Lung Cancer (NSCLC) Harboring ALK Fusions.	NCT05361564	Non-small Cell ...	Brigatinib	20 Years -	Yonsei University

Spots Global Cancer Trial Database for alk fusion

Every month we try and update this database with for alk fusion cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for alk fusion

Every month we try and update this database with for alk fusion cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for alk fusion cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.