For Children and Adolescents With Relapsed or Refractory Malignant Brain Cancer, Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma

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Trial Summary

Official Title

A Phase 1, Open-Label, Dose Escalation Study of CLR 131 in Children and Adolescents With Select Solid Tumors, Lymphoma, and Malignant Brain Tumors

Status

Not yet recruiting

Condition

Pediatric Solid Tumor, Pediatric Lymphoma, Pediatric Brain Tumor

Actual Start Date

July 2018

Estimated Primary Completion Date

September 2020

About the Trial

Dose Escalation Study of CLR 131 in Children and Adolescents with Relapsed or Refractory Malignant Brain Cancer, Neuroblastoma, Rhabdomyosarcoma, Ewing’s Sarcoma, and Osteosarcoma

Even with standard, highly toxic multimodality therapies and salvage regimen, most pediatric patients with primary metastatic or relapsed solid tumors are confronted with a poor prognosis. For these patients there is currently no accepted successful treatment regimen. There is a need for new drugs, including targeted radiopharmaceuticals, preferably with cancer-specific uptake and broad applicability for these rare pediatric malignancies.

CLR 131 is a radio iodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound (CLR1404) is radiolabeled with the isotope iodine-131 (I-131). CLR 131 has demonstrated tumor selective uptake across numerous adult and pediatric cancer cell types. Therapeutic efficacy has been demonstrated in various pediatric and adult-type cancer xenograft models, confirming the ability of CLR 131 to target tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in relapsed pediatric cancers and initial preclinical and clinical experience with radio iodinated CLR1404, Cellectar Biosciences has chosen to assess CLR 131 in a phase 1 pediatric trial.

Detailed Info

Brief Summary

The study evaluates CLR 131 in children and adolescents with relapsed or refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain tumors for which there are no standard treatment options with curative potential.

Study Phase

Phase 1

Estimated Enrollment

30

Estimated Primary Completion Date

September 2020

Study Type

Interventional

Interventions
  • Drug: CLR 131
Sponsor

Cellectar Biosciences, Inc.

Eligibility

Gender

Male & Female

2+

Age

2 years to 21 years

60+

Karnofsky score The Karnofsky score allows patients to be classified as to their functional impairment. Scores run from 100 to 0; the lower the Karnofsky score, the worse the survival rate for most serious illnesses. This score allows physicians to evaluate a patient's ability to survive chemotherapy for cancer.

Higher or Equal to 60%

Inclusion Criteria

All Patients

  • Previously confirmed (histological or cytological) pediatric solid tumor (e.g., neuroblastoma, sarcoma), lymphoma (including Hodgkin's lymphoma), or malignant brain tumors that are clinically or radiographically suspected to be relapsed, refractory, or recurrent for which there are no standard treatment options with curative potential
  • ≥ 2 years of age and ≤ 21 years of age at time of consent/assent
  • If ≥ age 16, Karnofsky performance status of ≥ 60. If < age 16, Lansky performance status ≥ 60
  • Platelets ≥ 75,000/µL (last transfusion, if any, must be at least one week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
  • Absolute neutrophil count ≥ 750/µL
  • Hemoglobin ≥ 10 g/dL (last transfusion must be at least one week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
  • Using the bedside Schwartz formula, age-based serum creatinine within 2 x upper limit of normal (ULN)
  • Alanine aminotransferase < 3 × ULN
  • Bilirubin < 2 × ULN

Patients who have undergone autologous bone marrow transplant must be at least 3 months from transplant.

  • Patients enrolling at dose levels > 30 millicurie (mCi)/m2 must have availability or ability to collect an autologous stem cell back-up product prior to CLR 131 administration. At minimum, 2 x 10^6/kg cryopreserved CD34+ cells/kg must be available.
  • Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol.
  • Patient or his or her legal representative has the ability to read, understand, and provide written informed consent for the initiation of any study-related procedures.
  • Female patients of childbearing potential must have a negative pregnancy test at screening and within 24 hours of dosing. It is recommended that female caregivers of childbearing potential have a negative pregnancy test within one week of dosing.
  • Patients of childbearing potential must practice an effective method of birth control while participating on this study to avoid possible damage to the fetus.

Patients with Pediatric Solid Tumor or Lymphoma

  • At least one measurable lesion with longest diameter of at least 15 mm. Patients with a lesion(s) that are determined to be Metaiodobenzylguanidine (MIBG) or positron emission tomography (PET) positive may be enrolled at the investigator's discretion, even if not associated with a measurable lesion of at least 15 mm.
  • Patients with known brain metastases must have completed any radiotherapy or systemic treatments for brain metastases prior to enrollment; by investigator assessment be considered stable with no new signs or symptoms for at least one month, and on a stable dose of steroids (unchanged for three weeks prior to screening).

Patients with Recurrent or Refractory Brain Tumors

  • At least one measurable lesion with longest diameter of at least 10 mm on any imaging sequence.
  • Patients with neurological deficits must be clinically stable at time of enrollment and able to complete all study related procedures. Patients with documented or newly diagnosed neurological deficits will be enrolled at the investigator's discretion.
  • Patients must be on a stable dose of steroids (unchanged for three weeks prior to screening)

Exclusion Criteria

  • Patients receiving active treatment for brain metastases or those that are likely to require active treatment during anticipated participation in this trial.
  • Central nervous system involvement unless previously treated with surgery, systemic therapy, or radiotherapy with the patient neurologically stable.
  • Antitumor therapy or investigational therapy, within 2 weeks of registration. For certain types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to skull-based metastases is not considered craniospinal radiation for the purposes of this study]), at least 3 months must have elapsed.
  • Patients previously treated with iodine-131 (131I)-MIBG who have already received a cumulative I-131 dose > 54 mCi/kg or who would exceed 54 mCi/kg by participating in this trial, are not eligible.
  • History of hypersensitivity to iodine
  • Any other concomitant serious illness or organ system dysfunction (including cardiac and pulmonary dysfunction) that in the opinion of the Investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
  • Major surgery within 6 weeks of enrollment
  • Known history of human immunodeficiency virus or uncontrolled, serious, active infection
  • Pregnancy or breast-feeding

Enrollment

For more information on enrollment into the current CLR 131 trial, please contact us or visit clinicaltrials.gov for location information.

Contact Us Visit ClinicalTrials.gov

Frequently Asked Questions

Clinical trials are research studies that involve people. Through clinical trials, doctors find new ways to improve treatments and the quality of life for people with disease.

Researchers design cancer clinical trials to test new ways to:

  • Treat cancer
  • Find and diagnose cancer
  • Prevent cancer
  • Manage symptoms of cancer and side effects from its treatment

Clinical trials are the final step in a long process that begins with research in a lab. Before any new treatment is used with people in clinical trials, researchers work for many years to understand its effects on cancer cells in the lab and in animals. They also try to figure out the side effects it may cause.

Any time you or a loved one needs treatment for cancer, clinical trials are an option to think about. Trials are available for all stages of cancer. It is a myth that they are only for people who have advanced cancer that is not responding to treatment.

Every trial has a person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the trial, called a protocol. The protocol explains what will be done during the trial. It also contains information that helps the doctor decide if this treatment is right for you. The protocol includes information about:

  • The reason for doing the trial
  • Who can join the trial (called “eligibility criteria”)
  • How many people are needed for the trial
  • Any drugs or other treatments that will be given, how they will be given, the dose, and how often
  • What medical tests will be done and how often
  • What types of information will be collected about the people taking part3

Clinical Trial Phases and Their Purpose(s)

Phase 1

  • Find a safe dose
  • Decide how the treatment/medicine should be administered
  • Determine how the new treatment may impact the people who take it

Phase 2

  • Determine if the treatment has an effect on certain cancers or cancer types
  • Determine how the new treatment may impact the people who take it

Phase 3

  • Compare and contrast the treatment with the current standard treatment

Phase 4

  • Monitor and further asses the long-term safety and efficacy of the treatment
  • According to the National Cancer Institute, clinical trials are finding and creating new ways of treating, diagnosing and even preventing cancer so that ultimately, care and quality of life for people with cancer can improve.1
  • In addition to testing new ways of treating and diagnosing cancer, clinical trials are also used to determine the best uses and combinations of existing therapies to combat cancer and to improve patient care and quality of life for cancer patients both during and after their treatments.1
  • Ultimately, thousands of people have volunteered over the years for clinical trials and it is because of those patients, and dedicated medical and research personnel that we now have so many breakthroughs in disease and cancer prevention within the last 50 years.2

Myth #1: Patients who are involved in clinical trials are treated like guinea pigs

FACT: Clinical trial patients often report that they have been treated with the utmost care, compassion and respect during their clinical trial treatment(s). Also, clinical trials are highly regulated and many safeguards have been put into place to protect patients and their best interest.6


Myth #2: Some patients receive placebos and some receive the real treatments

FACT: All patients who enroll in a clinical trial will receive the best treatment available to treat their type and stage of cancer. Placebos are very rarely used in cancer clinical trials and if they are, they are given in addition to the current standard of care and the patient is told that it is happening.4


Myth #3: Clinical trials are unaffordable and/or not covered by insurance

FACT: Volunteers for clinical trials rarely have to pay any costs related to participating in the trial. There are two types of costs associated with a clinical trial: research costs and patient care costs. Research costs are those associated with conducting the trial, such as data collection and management, research physician and nurse time, analysis of results, and tests performed purely for research purposes. These costs are usually covered by the sponsoring organization, such as the biopharmaceutical company, and are not the patient's responsibility. Patient care costs are costs that are not covered by the research sponsors doing the clinical trial, such as the costs for routine care including doctor visits, hospital stays, clinical laboratory tests, x-rays and other clinical trial-related activities that would be done even if you were not in the trial. Many health insurance carriers will cover patient care costs, but you should ask the clinical trial research team which costs will be your responsibility and also check with your health insurance carrier about the coverage they provide for clinical trial participants before making the decision about participating in a clinical trial.6


Myth #4: Clinical trials are only for people who have tried all other treatments and have run out of options.

FACT: Understanding the phases described above can help to answer this question. In some cases the answer may be yes – if nothing else is working a Phase 1 trial may help you further research for others with your disease (and has a small chance of making a difference for you as well.) But usually, people participate in clinical trials for other reasons. Cancer clinical trials are available for people at all stages of their disease.5


Myth #5: Once a patient agrees to be involved in a clinical trial, they are required to follow through to the end.

FACT: Clinical trials rely on voluntary participation. You are free to leave a clinical trial at any time, even after you have signed an informed consent and received the investigational drug or placebo. However, you should always let the clinical trial team know before you decide to leave the trial because some medicines cannot be stopped safely without a doctor’s help.6


Myth #6: If there is a clinical trial available that might help me, my doctor will definitely tell me about it.

FACT: Your doctor may not know about all available clinical trials that might benefit you. The National Institutes of Health has an online database that you, your family or doctor can search to find appropriate trials: www.clinicaltrials.gov. Alternatively, it’s often worth making contact with a patient advocacy organization to help you navigate the process. Many of them have tailored services that can help you with your search and help you understand the options.

 If you are thinking about participating in a clinical trial and have additional questions, you should talk to your doctor or a patient advocacy organization for your disease or condition.6

National and international regulations and policies have been developed to help ensure that research involving people is conducted according to strict scientific and ethical principles. In these regulations and policies, people who participate in research are usually referred to as "human subjects."

Clinical trials are reviewed by the country's regulatory department. For example, in the US, clinical trials are reviewed by the U.S. Food and Drug Administration (FDA) and in Canada, that review is done by Health Canada.

In addition, each hospital that conducts a clinical trial must have the study reviewed and approved by an Institutional Review Board (IRB). The IRB reviews all aspects of a clinical trial to make sure that the rights, safety, and well-being of trial participants will be protected. The IRB must also review ongoing trials at least yearly and, based on those reviews, can decide whether the trial should continue as initially planned or if changes should be made to improve participant protection. An IRB can stop a clinical trial if the researchers are not following the protocol or if the trial appears to be causing unexpected harm to the study participants.

An IRB must have at least five members, including one scientist, one person who is not a scientist, and one person who is not affiliated with the institution where the trial is taking place and who is not an immediate family member of someone who is affiliated with that institution. The nonscientist and the nonaffiliated member can be the same person. IRBs can also include doctors, nurses, social workers, chaplains, patient advocates, and other health care or community professionals. All members of an IRB are required to be educated about the IRB's purpose, functions, and responsibilities, as outlined in federal regulations. Trials taking place at multiple locations can involve multiple IRBs.

Clinical trials also may use a Data and Safety Monitoring Board (DSMB) or a safety monitoring committee to monitor the safety and progress of the trials.

A DSMB is a committee of doctors, statisticians, and others who are independent of the people, organizations, and institutions that are sponsoring, organizing, and conducting the clinical trial. Similar to IRBs, DSMBs review the progress of a clinical trial and participant safety, but they also review data on the effectiveness of the trial interventions. DSMB members are experts in clinical research and clinical trials. They ensure that trial data are complete, and they can stop a trial early if safety concerns arise or if an answer to the main research question is obtained earlier than expected. Stopping a trial early because the main research question has been answered may make it possible for people who are not in the trial to get access to an effective intervention sooner. DSMBs have scheduled meetings to review clinical data, and their meeting minutes or recommendations are forwarded to the IRBs.7

References:

  1. "Clinical Trials." National Cancer Institute. National Institutes of Health. http://www.cancer.gov/research/areas/clinical-trials
  2. "The Importance of Clinical Trials - Policy and Medicine." Policy and Medicine. Policy and Medicine Online. http://www.policymed.com/2010/05/the-importance-of-clinical-trials.html
  3. "What Are Clinical Trials?" National Cancer Institute. National Institutes of Health. http://www.cancer.gov/about-cancer/treatment/clinical-trials/what-are-trials
  4. "Placebo." National Cancer Institute. National Institutes of Health. http://www.cancer.gov/about-cancer/treatment/clinical-trials/what-are-trials/placebo
  5. "Top 10 Myths About Clinical Trials for Cancer." https://www.verywell.com/myths-about-clinical-trials-for-cancer-2249004
  6. "Debunking Common Myths About Clinical Trials." Debunking Common Myths About Clinical Trials. Catalyst Pharma. http://catalyst.phrma.org/debunking-common-myths-about-clinical-trials
  7. "Cancer Clinical Trials."National Cancer Institute, National Institutes of Health. http://www.cancer.gov/research/areas/clinical-trials

The safety and efficacy of the investigational use of this product has not been determined. There is no guarantee that the investigational use listed will be filed with and/or approved for marketing by a regulatory agency.