Maximum Tolerated Dose, Safety, and Efficacy of Rhenium Nanoliposomes in Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01906385
Recruitment Status : Recruiting
First Posted : July 24, 2013
Last Update Posted : October 26, 2018
Information provided by (Responsible Party):
Andrew Brenner, The University of Texas Health Science Center at San Antonio

Brief Summary:
While radiation is an essential component to the treatment of glioblastoma, it's use is limited due to toxicity when higher doses are attempted. Rhenium is a compund which releases radiation in small particles that are absorbed after only a fraction of an inch. This limited penetration means that high doses potentially can be given without the toxicity of other forms of radiation. In order for the radiaiton to be retained within the tumor, it has been packaged in microscopic fat like particles termed nanoliposomes. These facilitate the uptake of the radiation particles by the tumor. In order to better characterize this form of radiation therapy, it is being administered in patients who have failed other forms of therapy for glioblastoma. The treatment is administered by tubing inserted into the center of the tumor in the operating room. There are two portionms to this study. The first involves progressively increasing doses until the most tolerable dose can be identified. The second portion of the study involves a larger number of patients being treated at the determined most tolerable dose to better evalaute how well the treatment works.

Condition or disease Intervention/treatment Phase
Glioblastoma Astrocytoma Drug: Rhenium Liposome Treatment Phase 1 Phase 2

Detailed Description:

Rhenium-186 (186Re) (half-life 90 hours) is a reactor produced isotope with great potential for medical therapy. It is in the same chemical family as Technetium-99m (99mTc), a radioactive tracer that is the most commonly used isotope for diagnostic scintigraphic imaging in nuclear medicine. Like 99mTc, rhenium is not taken up by bone and is readily cleared by the kidneys. 186Re emits both therapeutic beta particles and every 10 isotope decays is associated with a gamma photon. The average 186Re beta particle path length in tissue of 2mm is ideal for treatment of solid tumors. Additionally, the emitted gamma photons have similar photon energy to those emitted by 99mTc, therefore allowing for imaging of the isotope within the body on standard nuclear imaging machines available in routine medical practice. Therefore, the 186Re isotope has great potential in CED applications of local therapy of solid tumors. However, a carrier is needed to deliver the isotope to the brain and maintain its localization at the desired site, as otherwise it would quickly disperse and be carried away from the site of injection by the circulatory system.

Liposomes are spontaneously forming lipid nanoparticles that have been well studied for over 30 years. Although larger liposomes can be manufactured, the most useful size range for drug carrier applications is 80-100 nm. Liposomes of this size are often referred to as nanoliposomes and have the ability to facilitate retention at the site of injection. A method for the efficient loading of liposomes with the to very high levels of specific activity has been developed. These rhenium-labeled nanoliposomes (186RNL) have shown great promise in preclinical studies 186RNL of glioblastoma that surpassed results typically seen with currently standard treatment modalities such as oral temozolomide or intravenous bevacizumab.

This is a single center, sequential cohort, open-label, dose-escalation study of the safety, tolerability, and distribution of 186RNL given by convection enhanced delivery to patients with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Dual Phase 1/2, Investigator Initiated Study to Determine the Maximum Tolerated Dose, Safety, and Efficacy of Rhenium Nanoliposomes in Recurrent Glioblastoma
Study Start Date : March 2015
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Rhenium Liposome Treatment Drug: Rhenium Liposome Treatment
At the time of stereotactic biopsy a catheter will be placed within the tumor using stereotactic guidance. Once the patient has adequately recovered from the procedure as determined by the neurosurgeon, 186RNL will be infused through the catheter at the predetermined dose. Spectroscopic imaging will then be obtained at predefined time points to visualize the distribution of the 186RNL as well as calculated the actual dose retained within the tumor. Patients will be monitored longitudinally for evidence of toxicity and response by MRI.

Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 90 days ]
    Evaluation of any toxicity associated with research treatment per Common Toxicity Criteria for Adverse Events.

Secondary Outcome Measures :
  1. Dose Distribution [ Time Frame: 3 days ]
    SPECT imaging of the radioacitve materials spread across the tumor and surrounding brain

  2. Response rate [ Time Frame: 90 days ]
    Evaluation of overall response rate by RANO criteria

  3. Survival [ Time Frame: 6 months ]
    Disease specific progression free survival

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Planned stereotactic biopsy as standard of care (ie, for confirmation of disease progression)
  2. At least 18 years of age
  3. Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
  4. Histologically confirmed glioblastoma
  5. Progression following both standard combined modality treatment with radiation and temozolomide chemotherapy, as well as anti-angiogenic therapy (ie, bevacizumab; patients not eligible for or refusing antiangiogenic therapy will also be allowed)
  6. For cohorts 1-3, tumor volumes limited to 1.5cc, as calculated under 4.1 Inclusion criteria.
  7. Recovered from toxicities of prior therapy to grade 0 or 1
  8. ECOG performance status of 0 to 2
  9. Life expectancy of at least 2 months
  10. Acceptable liver function:

    • Bilirubin ≤ 1.5 times upper limit of normal
    • AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN);
  11. Acceptable renal function:

    • Serum creatinine ≤1.5xULN
  12. Acceptable hematologic status (without hematologic support):

    • ANC ≥1000 cells/uL
    • Platelet count ≥75,000/uL
    • Hemoglobin ≥9.0 g/dL
  13. All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose

Exclusion Criteria:

  • The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible.
  • The subject is unable to undergo MRI scan (eg, has pacemaker).
  • The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study drug.
  • The subject is pregnant or breast-feeding.
  • The subject has serious intercurrent illness, such as:

    • hypertension (two or more blood pressure [BP] readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment
    • Non-healing wound, ulcer, or bone fracture
    • Significant cardiac arrhythmias
    • Untreated hypothyroidism
    • Unhealed rectal or peri-rectal abscess
    • Uncontrolled active infection
    • Symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug
  • Myocardial infarction, stroke, transient ischemic attack within 6 months

    • Gastrointestinal perforation, abdominal fistula, intra- abdominal abscess within 1 year
    • History or clinical evidence of pancreatitis within 2 years
  • The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding
  • The subject has received any of the following prior anticancer therapy:

    • Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy (RIT), or intra-operative radiotherapy (IORT) to the target site. SRS is allowed as long as the target lesion for this study has not been the treatment target.
    • Targeted therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 7 days or 5 half-lives, whichever is shorter, prior first dose of study drug
    • Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
    • Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug
    • Prior treatment with carmustine wafers

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01906385

Contact: Epp Goodwin 450-5798
Contact: Ofelia Romero 210-450-1810

United States, Texas
The Cancer Therapy and Research Center at UTHSCSA Recruiting
San Antonio, Texas, United States, 78229
Principal Investigator: Andrew J Brenner, M.D., Ph.D.         
Sub-Investigator: John R Floyd, M.D.         
Sub-Investigator: William T Phillips, M.D.         
Sponsors and Collaborators
Andrew Brenner
Principal Investigator: Andrew J Brenner, MD, PhD The University of Texas Health Science Center at San Antonio

Responsible Party: Andrew Brenner, Assistant Professor, The University of Texas Health Science Center at San Antonio Identifier: NCT01906385     History of Changes
Other Study ID Numbers: CTRC 12-02
14-450X ( Other Identifier: UT Health San Antonio )
First Posted: July 24, 2013    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Andrew Brenner, The University of Texas Health Science Center at San Antonio:
Brain Tumor

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue