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Clinical Trials Monthly - April 2012

Clinical Trials Monthly presents new and important trials that may benefit your patients. This month we’ve included trials for leukemia, bladder cancer, breast cancer, lymphoma, melanoma, multiple myeloma, and prostate cancer. Each study summary has a link to specific details about the trial in our online Clinical Trials Database. The complete list of all trials recruiting participants at Seattle Cancer Care Alliance can be found at www.seattlecca.org/clinicaltrials.

This Month’s Featured Clinical Studies

Acute Myeloid Leukemia

  • PLX3397 for adult relapsed/refractory acute myeloid leukemia (NCT01349049)
  • Tosedostat with cytarabine or decitabine for newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome (NCT01567059)

Bladder Cancer

  • OGX427 and chemotherapy for metastatic bladder cancer (NCT01454089

Breast Cancer

  • Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer (NCT01419197)
  • Combination of high-dose methotrexate and intrathecal liposomal cytarabine for leptomeningeal metastases with/ without parenchymal brain involvement for breast cancer brain metastasis (NCT00992602)

Lymphoma

  • Bendamustine, dexamethasone, plus filgrastim for peripheral stem cell mobilization for refractory or recurrent lymphoma or multiple myeloma (NCT01110135)

Melanoma

  • Ipilimumab in two doses for previously treated or untreated unresectable or metastatic melanoma (NCT01515189)

Multiple Myeloma

  • Lenalidomide, bortezomib, dexamethasone vs. high-dose treatment with transplant for multiple myeloma patients up to age 65 (NCT01208662)
  • Lenalidomide/dexamethasone with or without elotuzumab for newly diagnosed multiple myeloma (NCT01335399)

Non-Hodgkin’s Lymphoma

  • DCDS4501A for non-Hodgkin’s lymphoma and chronic lymphocytic leukemia (NCT01290549)

Ovarian Cancer

  • Vaccine therapy for stage III-IV ovarian cancer (NCT01322802)

Prostate Cancer

  • ARN-509 for castration-resistant prostate cancer (NCT01171898)
  • OGX-427 for castration-resistant prostate cancer (NCT01120470)
  • OGX-011 with docetaxel/prednisone for metastatic prostate cancer (NCT01188187)

Acute Myeloid Leukemia

Phase I/II Safety and Efficacy of PLX3397 in Adults with Relapsed or Refractory Acute Myeloid Leukemia (AML) (NCT01349049)

AML patients with internal tandem duplication (ITD) of the Flt 3 gene have a poor prognosis. PLX3397 inhibits the abnormal tyrosine kinase formed as a consequence of this product of this abnormal gene in relapsed AML and Flt 3 ITD.

The purpose of this study is to evaluate the safety of PLX3397 at three dose levels and explore the efficacy in patients with relapsed or refractory AML.

Investigator: John M. Pagel, MD, PhD

Tosedostat with Cytarabine or Decitabine for Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome (NCT01567059)

This study will examine a new oral chemotherapy drug called tosedostat given in combination with cytarabine or decitabine for older, newly diagnosed patients with acute myeloid leukemia or highrisk myelodysplastic syndrome. The median survival for these patients is approximately one year. The goal of this study is to improve that outcome. Cytarabine and decitabine are standard drugs. Tosedostat is an experimental drug thought to work by decreasing the availability of amino acids in cells. It has been shown in early studies to have activity against a variety of cancers, including relapsed leukemias.

InvestigatorJohn M. Pagel, MD, PhD

Bladder Cancer

A Phase II Study Comparing Chemotherapy in Combination with OGX-427 or Placebo in Patients with Bladder Cancer (NCT01454089)

Transitional cell cancer (TCC), the most common histological type of bladder cancer, can often be managed surgically with a good prognosis. However, about 25 percent of patients with TCC will present with advanced or metastatic disease—and a significant proportion of those who do have radical cystectomy will recur and evolve to metastatic disease within five years. Systemic chemotherapy has been the treatment of choice for inoperable, locally advanced, or metastatic TCC. This randomized doubleblind study evaluates the safety and efficacy of the standard chemotherapy for bladder cancer (gemcitabine and cisplatin) in combination with either OGX-427 (at 600 mg or 1000 mg) or placebo in patients with advanced TCC who have not previously received chemotherapy for metastatic disease and are not candidates for potential curative surgery or radiotherapy. OGX-427 is an experimental antisense drug that inhibits expression of heat shock protein 27 (Hsp27), a cell survival protein that is overproduced by cancer cells in response to chemotherapy.

Investigator: Evan Ya-Wen Yu, MD

Breast Cancer

A Phase III Randomized, Multi-Center, Two-Arm, Open-Label Trial to Evaluate the Efficacy of T-DM1 Compared with Treatment of Physician’s Choice in Patients with HER2-Positive Metastatic Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-Directed Therapy (NCT01419197)

This randomized, multi-center, two-arm, open-label study will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1), an HER-2 monoclonal antibody, in comparison with treatment of the physician’s choice in patients with metastatic or unresectable locally advanced/recurrent HER2-positive breast cancer. Eligible patients will be randomized to receive either T-DM1 (3.6 mg/kg intravenously) every 21 days or treatment with the physician’s choice. Patients will stay on the study until disease progression or unacceptable toxicity occurs.

Investigator: V.K. Gadi, MD, PhD

Phase II Study of the Combination of High-Dose Methotrexate and Intrathecal Liposomal Cytarabine in Patients with Leptomeningeal Metastases with or without Parenchymal Brain Involvement (NCT00992602)

This multi-center study will examine intravenous high-dose methotrexate given in combination with liposomal cytarabine (also called Depocyt) administered directly into the cerebrospinal fluid to treat breast cancer that has metastasized to the thin tissues that cover the brain and spinal cord. Current standards for treating leptomeningeal metastases are uncertain and complications from intrathecal therapy can be serious. The goal of this study is to determine the effects of the combination therapy on patient survival, toxicities, presence of malignant cells in the CSF, and patient quality of life.

Methotrexate is approved by the Food and Drug Administration (FDA) to treat cancer, including breast cancer. Depocyt is approved by the FDA to treat cancer that has spread into the spinal fluid. Neither of the drugs is experimental but the combination of these two drugs has never been tested in metastatic breast cancer.

Investigator: Maciej Mrugala, MD, PhD, MPH

Lymphoma

A Phase II Study of Bendamustine, Dexamethasone, and G-CSF for Peripheral Blood Hematopoietic Stem Cell Mobilization (NCT01110135)

Chemotherapy, such as etoposide, cyclophosphamide, and dexamethasone, given before a peripheral stem cell transplant, can stop the growth of cancer cells by preventing their division or killing them. These agents can also be used to stimulate the bone marrow to produce more stem cells which can then be collected and stored for stem cell transplant. Giving colony stimulating factors, such as G-CSF (filgrastim) either alone, or after chemotherapy, helps blood stem cells move from the bone marrow into the bloodstream. Once circulating, the stem cells can be collected and stored for transplantation. Bendamustine hydrochloride is another chemotherapy drug that has recently demonstrated efficacy in the treatment of patients with lymphoma and multiple myeloma. This Phase II trial is studying how well giving bendamustine hydrochloride in combination with etoposide, dexamethasone, and subcutaneous filgrastim, works in achieving full peripheral blood stem cell mobilization as measured by harvest of an adequate number of stem cells by leukapheresis. Patients enrolled in this study will be transplant-eligible with refractory or recurrent lymphoma (e.g., B-cell, T-cell, Hodgkin’s lymphoma) or multiple myeloma.

Investigators: Damian J. Green, MD and Ajay K. Gopal, MD

Melanoma

A Randomized Double-Blind Phase III Study of Ipilimumab Administered at 3 mg/kg vs at 10 mg/kg in Subjects with Previously Treated or Untreated Unresectable or Metastatic Melanoma (NCT01515189)

Ipilimumab (Yervoy) is an antibody that blocks human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Approved in 2011 for the treatment of unresectable or metastatic melanoma at a dose of 3 mg/kg, the agent increases median overall survival but has the potential to cause serious immune-related side effects due to T cell activation and proliferation. The purpose of this study is to see if there is a difference in survival in patients who receive the approved dose (3 mg/kg) versus patients who receive an investigational dose (10 mg/kg).

Eligible patients must have metastatic melanoma, and may have had any number of prior treatments for melanoma, except for B-Raf inhibitors (such as vemurafenib), and other CTLA-4 or PD-1/PD-L1 antagonists or CD137 agonists. PatientsThey may not have a history of autoimmune disease (like rheumatoid arthritis or lupus).

Eligible patients are assigned randomly to receive either 3 mg/kg of ipilimumab or 10 mg/kg of ipilimumab. This study is blinded; neither the patient nor the doctor will know which dose the patient is receiving.

Investigator: Kim A. Margolin, MD

Multiple Myeloma

Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone with or without High-Dose Treatment with SCT in Multiple Myeloma Patients up to Age 65 (NCT01208662)

This study compares the value of high dose melphalan and stem cell transplant (HDT) when lenalidomide, bortezomib, and dexamethasone (VRD) are used for initial therapy. All patients receive VRD induction but the comparison is eight cycles of VRD alone to five cycles of VRD with HDT.

In the era of novel drugs, the need for high-dose therapy (HDT) in the initial management of multiple myeloma in younger patients has been questioned. In this study, HDT would be considered superior to conventional dose treatment if it prolongs progression-free survival by at least nine months or more.

Lenalidomide, bortezomib, and dexamethasone are FDA-approved drugs but have not been approved in combination for multiple myeloma or any other type of cancer. Bortezomib is currently approved for the treatment of multiple myeloma. Lenalidomide is approved for use with dexamethasone for patients with multiple myeloma who have received at least one prior therapy and for the treatment of certain types of myelodysplastic syndrome. Dexamethasone is commonly used alone or with other drugs to treat multiple myeloma. Melphalan and cyclophosphamide, are FDA-approved and used during stem cell collection and transplantation. Both are already used to treat multiple myeloma. Testing suggests that this combination may help treat newly diagnosed multiple myeloma.

Investigator: William I. Bensinger, MD

A Phase III, Randomized, Open-Label Trial of Lenalidomide/Dexamethasone with or without Elotuzumab in Subjects with Previously Untreated Multiple Myeloma (NCT01335399)

The purpose of the study is to determine whether the addition of elotuzumab to lenalidomide/low-dose dexamethasone treatment will increase the progression-free survival (PFS) in newly diagnosed, symptomatic multiple myeloma. Elotuzumab is a humanized monoclonal antibody to cell surface glycoprotein 1 (CS1), which is highly expressed on myeloma cells. Eligible patients will have not received any prior systemic anti-myeloma therapy and have measurable disease but are not candidates for HDT plus stem cell transplantation because of age (≥?65 years) or coexisting conditions.

Investigator: William I. Bensinger, MD

Non-Hodgkin’s Lymphoma

An Open-Label, Multi-Center, Phase I Trial of the Safety and Pharmacokinetics of Escalating Doses of DCDS4501A in Patients with Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia (NCT01290549)

Study Update: Only 26 patients have been treated on this trial so far, but preliminary results are encouraging. Ten patients were discontinued early due to disease progression, but all of these patients had been on the lower doses used earlier in the trial. We are now treating all patients at higher doses, currently 1.8 or 2.4 mg/kg, and these patients are seeing measureable reduction of tumor with minimal side effects. Three patients at our center have been scanned so far. One showed a 13 percent reduction after seven cycles (this patient was treated at a lower dose earlier in the study but has now been dose-escalated). The other two patients at our center both experienced 33 percent reductions after four cycles.

None of our patients have experienced disease progression on this dose-escalation study. The study drug is being well-tolerated. The most common side effect is neutropenia, which can be supported after the first two cycles.

Investigator: Oliver W. Press, MD, PhD

Ovarian Cancer

A Phase I Trial of the Safety and Immunogenicity of a DNA Plasmid Based Vaccine Encoding the Amino Acids 1-163 of Insulin-Like Growth Factor Binding Protein-2 (IGFBP-2) in Patients with Advanced Ovarian Cancer (NCT01322802)

This Phase I trial is studying the side effects of vaccine therapy in treating patients with stage III-IV ovarian cancer. IGFBP-2 is a protein found in the blood and tumor cells of most women who have been diagnosed with ovarian cancer. High levels of IGFBP-2 have been associated with more invasive disease. One strategy for reducing IGFBP-2 on tumor cells is to generate an immune response against the tumor cells expressing IGFBP-2. Immunizing patients with a vaccine against IGFBP-2 may do this.

The vaccine is made up of DNA isolated from a bacteria into which a portion of the IGFBP-2 protein code (DNA) is inserted. In this trial, we are studying the safety of the vaccine (monthly intradermal injections for three months). In addition, we will measure immune response to help determine how effective the vaccine is in stimulating the immune system to recognize IGFBP-2.

Patients with advanced stage ovarian cancer (stages III or IV) who have been treated to complete remission with standard therapies may be eligible for this trial.

Investigator: Mary (Nora) L. Disis, MD

Prostate Cancer

Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 in Castration-Resistant Prostate Cancer (CRPC) (NCT01171898)

This is a Phase I/II study to assess the safety and activity of ARN-509, a second-generation anti-androgen, in men with advanced castration-resistant prostate cancer. Patients will first be enrolled into Phase I of the study to identify a tolerable dose for the Phase II portion of the study. In Phase II, patients will be enrolled to evaluate the safety and activity of ARN-509. This study is open to three different groups of patients, including those with nonmetastatic CRPC, those with metastatic CRPC who are treatment-naïve, and those with metastatic CRPC who post-abiraterone. This study is not open to patients with distant metastases; prior treatment with MDV3100, abiraterone, or ketoconazole; nor with concurrent treatment with medications known to have seizure potential.

Investigator: Celestia S. Higano, MD

Comparison of Docetaxel/Prednisone to Docetaxel/Prednisone in Combination with OGX-011 in Men with Prostate Cancer (NCT01188187)

This Phase III study hopes to confirm that adding OGX-011 (custirsen) to standard first-line docetaxel/prednisone treatment can slow tumor progression and enhance survival outcomes compared to standard first-line docetaxel/prednisone treatment alone. This will be a randomized, open-label, multi-center, international trial.

Treatment will consist of docetaxel/prednisone/custirsen vs. docetaxel/prednisone. A total of at least 1,000 patients will be randomized. Those eligible have either progressive measurable disease, bone scan progression, or increasing serum PSA level. OGX-011 is an antisense oligonucleotide that inhibits expression of clusterin, a chaperone protein that promotes cancer cell survival and treatment resistance.

Investigator: Celestia S. Higano, MD

OGX-427 in Castration-Resistant Prostate Cancer Patients (NCT01120470)

This Phase II study will evaluate the anti-tumor effects of OGX-427 plus low-dose prednisone versus low-dose prednisone alone in men with castration-resistant (also known as hormone-refractory) prostate cancer who have not previously received chemotherapy for metastatic or locally recurrent disease. The purpose is to determine whether OGX-427 is able to slow the progression of prostate cancer and limit the symptoms of disease. OGX-427 is an inhibitor of heat shock protein 27, which is overexpressed in various tumor cells and has been associated with treatment resistance and negative clinical outcomes.

Investigator: Evan Ya-Wen Yu, MD

Referral or Consultation

To discuss your patients’ treatment options with an SCCA physician, please call our intake office at (206) 288-SCCA (7222) or (800) 804-8824. To read the full description of each trial or enroll your patients online, please visit www.seattlecca.org/clinicaltrials.

 


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