Nanotechnology in Clinical Trials
As successful as the Alliance has been in using nanotechnology to address and solve many important questions in the laboratory, the ultimate measure of the programís success lies in the translation of research discoveries to the clinic. Currently, several nanotechnology-enabled diagnostic and therapeutic agents developed by Alliance investigators are in clinical trials, and many more are nearing that goal.
A few examples of promising new Alliance-developed diagnostics and therapies based on nanotechnology are listed below:
- Drs. Caius Radu, Owen Witte and Michael Phelps at the Nanosystems Biology Cancer Center (Caltech/UCLA CCNE) have developed a series of positron emission tomography (PET) imaging agents. These agents, known as the [18F]-FAC family of PET imaging agents, are being tested for use in assigning patients for chemotherapy with drugs such as gemcitabine, cytarabine, fludarabine, and others that are used to treat cancers including metastatic breast, non-small cell lung, ovarian, and pancreatic, as well as leukemia and lymphomas. Tumors that are responsive to these drugs show up as bright images in PET scans when patients are first dosed with [18F]-FAC. Biodistribution studies have been conducted in eight healthy volunteers. Clinical development is being conducted by Sofie Biosciences.
- At the Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer (NANO-TUMOR) (University of California, San Diego CCNE), Dr. Thomas Kipps has developed a chemically engineered adenovirus nanoparticle to deliver a molecule that stimulates the immune system. Phase I clinical trials, being run jointly by Memgen and the Leukemia & Lymphoma Society, are underway in patients with chronic lymphocytic leukemia (CLL). An ongoing Phase I dose escalation study is evaluating patients who received direct intranodal injection of the chemically-engineered virus. Systemic clinical effects have been observed following a single intranodal injection with significant reductions in leukemia cell counts and reductions in the size of all lymph nodes and spleen. Injections were well tolerated with grade 2 or less toxicity, generally lasting less than 48 hours after injection. One patient treated went into complete remission.
- Calando Pharmaceuticals, founded by Dr. Mark Davis at the Caltech/UCLA CCNE, is conducting clinical trials with a cyclodextrin-based nanoparticle that safely encapsulates a small-interfering RNA (siRNA) agent that shuts down a key enzyme in cancer cells. This open-label, dose-escalating trial of CALAA-01 is testing the safety of this drug in patients who have become resistant to other chemotherapies.
- Cerulean Pharma, Inc. is conducting clinical trials of a cyclodextrin-based polymer conjugated to camptothecin. This trial is also an open-label, dose-escalation study of CRLX101 (formerly named IT-101) administered in patients with solid tumor malignancies. Calando Pharmaceuticals, founded by Dr. Mark Davis at the Caltech/UCLA CCNE, initiated the development of and retains the rights to CRLX101.
- At the Siteman Center of Cancer Nanotechnology Excellence (Washington University CCNE), Drs. Gregory Lanza and Samuel Wickline have developed a nanoparticle magnetic resonance imaging (MRI) contrast agent that binds to the αvβ3-intregrin found on the surface of the newly developing blood vessels associated with early tumor development. Kereos, which was founded by Alliance investigators, is conducting Phase I clinical trials with this agent to assess its utility in the early detection of cancer.
- Diagnostic company Nanosphere, founded by Dr. Chad Mirkin to commercialize technology developed at the Nanomaterials for Cancer Diagnostic and Therapeutics Center (Northwestern University CCNE) has already received FDA approval for a nanosensor test for the drug Coumadin. This same technology can be easily adapted to detect important cancer biomarkers, such as prostate specific antigen (PSA) or to measure blood levels of anticancer agents. In fact, a joint project between Nanosphere, the Northwestern CCNE, and the Robert H. Lurie Comprehensive Cancer Center is conducting a clinical study using human tissue samples to monitor very low levels of PSA to determine if such measurements, which are well beyond the sensivity of conventional PSA assays, can provide early warnings of disease recurrence.
- Dr. Ralph Weissleder, an investigator at the MIT-Harvard Center for Cancer Nanotechnology Excellence, is leading a clinical trial to determine if lymphotrophic superparamagnetic nanoparticles developed at the CCNE can be used to identify small and otherwise undetectable lymph node metastases.
- The Integrated Blood Barcode (IBBC) chip, developed by Dr. James Heath at the Caltech/UCLA CCNE, is now undergoing validation tests to measure the levels of approximately 800 miRNAs from 21 melanoma patients before and after therapy.
- Clinical trials are scheduled to begin later this year on a new type of CT scanner, developed by Dr. Otto Zhou at the Carolina Center of Cancer Nanotechnology Excellence (University of North Carolina CCNE) that uses carbon nanotubes as the x-ray source. This new scanner, developed through a joint venture with Xintek, founded by CCNE members, and Siemens, a leader in medical imaging, contains 52 nanotube x-ray sources and detectors arranged in a ring, a configuration that eliminates the need to move the x-ray source and increases the precision and speed of CT scanning, which in turn, could make CT scanning a prefered method for detecting small tumors.
- Discussions have begun with the FDA to start clinical trials using carbon nanotubes to improve colorectal cancer imaging. This imaging agent and associated is being developed by Dr. Sanjiv Sam Gambhir from the Center for Cancer Nanotechnology Excellence Focused on Therapy Response (Stanford University CCNE).
- BIND Biosciences, founded by Drs. Robert Langer and Omid Farokhzad of the MIT-Harvard CCNE, initiated a Phase 1 Clinical Study of its lead compound - BIND-014. BINDís targeted nanoparticles consist of a polymer matrix, therapeutic payloads, functional surface moieties, and targeting ligands which allow for particle optimization (i.e., accumulation in target tissue, avoidance of being cleared by immune system, and delivery of drug with desired release profile). The Phase 1 study has an ascending, intravenous dose design to assess the safety, tolerability, and pharmacokinetics of BIND-014 in patients with solid tumors. The primary objective of the study is to determine the maximum tolerated dose of BIND-014 and to assess preliminary evidence of antitumor activity. Patients are currently being screened for eligibility in this clinical trial, which is being conducted at the Virginia G. Piper Cancer Center at Scottsdale Healthcare in Scottsdale, Arizona in collaboration with the Translational Genomics Research Institute (TGen) and the Scottsdale Healthcare Research Institute.