Instructions and Call for Patient Participation in The University of Michigan Judith Tam ALK Lung Cancer Research Initiative
The University of Michigan Judith Tam ALK Lung Cancer Research Initiative is recruiting ALK positive NSCLC patients for extensive and sustained studies of the course of each individual’s disease. Their research is enabled by the continuing donation of patients’ blood samples, tumor tissue samples, and/or malignant fluids, as each may be available over time for individual patients.
The following steps are required for a patient to participate in the study. This process is likely to vary by patient at the discretion of the patient’s oncologist, the UMichigan team, and of course the patient’s circumstances. The initial process will take some time, so please start working with UMichigan long before you may have a biopsy sample available.
Dr. Sofia Merajver and a student at the Rogel Cancer Center at the University of Michigan look up at cells in medium in the lab.
1) To start, the patient contacts the UMichigan study team via email at ALK-Initiative@med.umich.edu and provides a brief introduction.
2) The patient coordinator at UMichigan provides an intake questionnaire.
3) The patient answers the questionnaire and returns it to the patient coordinator at UMichigan.
4) The patient’s information is forwarded to Dr. Angel Qin and/or Dr. Sofia Merajver, co-leads of the Initiative, for review.
4) The coordinator connects with the patient and explains the study, reviews eligibility, and answers any questions.
5) The patient reviews and signs the Informed Consent form.
6) The patient introduces his/her oncologist to the UMichigan study and/or chooses to go to UMichigan him/herself for consultation.
7) The UMichigan team offers an introductory Zoom meeting with the patient’s oncologist to discuss the study participation and answer questions.
8) A Material Transfer Agreement (MTA) between the University of Michigan and the patient’s treating hospital/institution is required to be signed by an officer of both institutions, unless the patient has their treatment at UMichigan, or at an institution with an MTA already in place.
9) If the patient is having his/her biopsy at his/her home institution, then, upon recurrence, a biopsy or fluid extraction is performed with appropriate quantities obtained for both commercial testing and research purposes if possible.
10) If there is enough tissue available, the patient’s treating institution sends a portion of the biopsy material out for NGS and other testing, as required, and the remainder to UMichigan for research.
11) The research portions of the patient’s blood, fluid, and/or tissue samples from a biopsy, as requested and/or as they may become available, are shipped overnight within twenty-four hours in the study-provided cooler boxes at four degrees Celsius.
12) If the biopsy is performed at UMichigan, then the patient’s oncologist informs UMichigan which commercial tests and laboratories are to be used. UMichigan prioritizes biopsy samples for the patients’ clinical and approved tests ordered by their oncologist, including commercial NGS testing, and any remaining biopsy samples are utilized by UMichigan researchers to advance their studies. UMichigan then provides the patient’s oncologist with the results of testing as soon as they are available.
13) Any remaining biopsy samples are utilized by UMichigan researchers to advance their studies.
Tumor biopsy material and/or malignant fluids will be used in the lab to attempt to grow organoids, which are 3-dimensional masses of tissue that are similar to the tumor itself. A panel of FDA-approved and yet-to-be approved drugs will be tested on these organoids to determine whether they effectively kill the cultured cells of that particular patient. The selected drugs will be individualized to a patient’s treatment history and sequencing data. Tumor samples of a centimeter or more that have been removed by surgical resection or excision will also be used for studies of cancer development in mice that have been engrafted with the human immune system. When implanted with tiny fragments of human cancer material, these mouse models allow the UMichigan researchers to study the course of ALK-positive lung cancer development at the cellular level from its very inception and through various stages of progression and mutation.
The purpose of testing an array of drugs against biopsy material and malignant fluid-derived organoids is to understand how well these drugs work to kill the cancer cells for that specific patient’s disease and how the cancer resists them. Organoids are studied to identify vulnerabilities they may have to varying therapies and how they change molecularly over time. As this project evolves, the number of patient samples tested will continue to grow, the research knowledge base will expand, and certain regulatory requirements will be met. It is hoped that these studies will eventually allow the provision of predictive information to a patient’s oncologist about standard of care alternatives and about other novel treatments that might otherwise not be considered. The motivation to provide utility to patients as soon as possible is primary to the Initiative.
Larger tumor samples are also used for organoid development and drug testing. Fragments of these tumor samples are additionally implanted within mice with humanized immune systems to discover the very earliest cellular and molecular changes in lung tissue that cause ALK+ NSCLC. Techniques are being developed to capture the entire spectrum of changes from normal lung tissue cells to advanced tumor cells in mouse models and to understand the genetic factors involved in tumor initiation. In the longer term, these insights will hopefully be used to guide strategies for early detection, intervention, disruption of cancer progression, and ultimately to cure ALK+ lung cancer.
A series of patients’ blood samples drawn over an extended period will be used to track the amount and mutational character of circulating tumor cells (CTCs). These are cells that are shed from the primary tumor and travel through the lymph or blood systems, potentially enabling metastasis. CTCs are easier and less harmful to access than tumor cells, enabling tumor profiling at multiple time points. They are important for monitoring a patient’s prognosis, as they are potential metastatic seeds for tumor migration. They serve as blood-born biomarkers that can dynamically provide significant mutational information. Measuring the number of CTCs in the patient’s blood can be useful for monitoring treatment; a tumor size decrease or lack thereof may mean that the treatment is working, while an increase may predict that disease recurrence or advancement is impending or ongoing. The UMichigan ALK Initiative team is developing advanced methods for detecting, isolating, and studying CTCs from a series of ALK patients’ blood samples over time. The ultimate goal is to significantly improve the diagnostic treatment of ALK-positive NSCLC by providing a non-invasive real-time method of molecular profiling and monitoring disease status.
All this research depends upon ALK-positive NSCLC patients generously donating their blood, tissue, and fluids in collaboration with their oncologists, their own clinical institutions, and the UMichigan team. It begins by the patient contacting the study team at ALK-Initiative@med.umich.edu and connecting with its patient coordinator, who will provide an intake questionnaire to gather more information. This patient information will be forwarded to Dr. Angel Qin and/or Dr. Sofia Merajver, co-leads of the Initiative. The coordinator will explain the study, review eligibility, and answer any questions. A process of compassionate conversation leading to a realistic review and understanding of the Informed Consent form is undertaken. The required Informed Consent form can then be signed if the patient is interested in participating in the study. UMichigan is seeking to collect patient samples at various timepoints of tissue, fluid, and blood, so cancer progression is not a requirement to become involved in the research study. Concurrent blood and tissue/fluid samples are preferred where possible. There are no exclusions based on sample size, but a tissue biopsy of at least one centimeter in size is preferred. All remotely collected samples need to be shipped overnight within twenty-four hours in the cooler boxes provided by the study at four degrees Celsius.
A Material Transfer Agreement (MTA) between the University of Michigan and the patient’s treating hospital/institution is required to be signed by an officer of both institutions. The patient’s treating hospital/institution is wherever the biopsy, fluid draw, or blood draw takes place (to be defined during the intake process). A patient-identified physician sponsor is essential to the process of getting the agreement through. This sponsorship is to be initiated and driven by the patient, starting with an introductory email from the patient to both the physician and the UMichigan team. An introductory Zoom meeting with the identified physician to discuss the study participation and answer questions is offered by the UMichigan doctors. Established MTA locations are evolving but currently include University of Colorado, Dana-Farber Cancer Institute, UCSF, and Tom Baker Cancer Center. In-process locations include Mayo Clinic, Henry Ford Health Systems, and MD Anderson (subject to change). Patients are encouraged to reach out to UMichigan as soon as possible and not wait for a disease event, so that an MTA can be established proactively.
If UMichigan is receiving a chunk of biopsy tissue or needle biopsy-derived tissue from the patient’s outside institution through the MTA, then the patient’s treating physician will be the one sending out biopsy material for commercial testing, and UMichigan will only receive the additional tissue/passes for research. The operating room surgeon/pathologist would determine how to split the sample and decide if there is enough material to delegate for research purposes. In all cases the surgery or needle biopsy will be at the surgeon/provider’s discretion based on patient safety. UMichigan does not require a certain amount of tissue or number of passes to be performed.
The option may be available for a patient to participate by going to UMichigan for a second opinion and consulting appointment with Dr. Qin, if the patient has consented and there is a clinical indication for a biopsy and/or blood donation. This can be discussed between the patient and the UMichigan study team prior to scheduling the appointment. For patients who are getting their biopsies performed at UMichigan, all patients’ blood, fluid, and tissue samples provided to the Initiative will be prioritized for appropriate clinical and approved tests first, including commercial NGS testing, with the remainder of the collected specimens used for the UMichigan ALK Initiative studies. If requested, the patient’s oncologist will be given the opportunity to define the desired commercial tests, select laboratories, and be promptly provided with the results of such testing as they become available.
The University of Michigan Judith Tam ALK Lung Cancer Research Initiative was made possible by a $7.6M gift from the Judith and Richard Tam Foundation. The gift is intended to accelerate progress in discoveries related to the pathogenesis, progression, treatment, and prevention of ALK-driven lung cancers. The overarching purpose is to foster rapid adoption of key discoveries that directly enhance the quality and length of patients’ lives. UMichigan has assembled a team of clinical and scientific experts in cancer metastasis, thoracic oncology, thoracic surgery, genetics, molecular pharmacology, cell biology, pathology, organoid development, data science, biomedical engineering, and more. Since its inception in late 2021, the UMichigan ALK Initiative team has made extraordinary progress in achieving its objectives, assembling a talented staff, establishing strong platforms, developing a solid strategic plan, and advancing the science beyond previous limits. The next phase of research acceleration will involve a synergistic collaboration with the ALK Positive, Inc. medical committees, as supported by the 3,000+ patients that participate in the ALK Positive support group on Facebook, and the much larger community of ALK+ patients and caregivers worldwide.
ALK Positive, Inc. is a 501(c)3 not-for-profit organization with the mission to improve the life expectancy and the quality of life for ALK-positive patients worldwide.
Edited by: Jeffrey M. Sturm, BS, MA, MBA
Research Acceleration Committee Member
Clinical Trials Committee Member
Board Member
ALK Positive, Inc. www.alkpositive.org
Advisory Board Member, UofMichigan ALK NSCLC Research Initiative
8-year ALK Positive NSCLC Survivor