Targeted Therapy Clinical Trials in Progress

Breast Cancer

Chemotherapy With or Without Trastuzumab After Surgery for Invasive Breast Cancer

This phase III study is comparing chemotherapy alone to chemotherapy plus trastuzumab in women with node-positive or high-risk, node-negative HER2-low invasive breast cancer. The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination. The chemotherapy regimen includes six cycles of docetaxel plus cyclophosphamide or four cycles of doxorubicin plus cyclophosphamide followed by weekly paclitaxel. The primary outcome measure is invasive disease-free survival. Secondary outcome measures include the following: disease-free survival; breast cancer-free survival; recurrence-free interval; overall survival; occurrence and frequency of adverse events; change in HER2 mRNA level; and Fcγ receptor polymorphism. The study has a target enrollment of 3260 women and with an estimated primary completion date of January 2017.

Sponsor: National Cancer Institute

ClinicalTrials.gov Identifier: NCT01275677

Chemotherapy Plus Lapatinib or Trastuzumab for HER2/Neu-Positive Metastatic Breast Cancer

This phase III study will evaluate the use of taxanebased chemotherapy with lapatinib or trastuzumab as first-line therapy for women with HER2/neu-positive metastatic breast cancer. The primary outcome measure is progression-free survival. Secondary outcome measures include overall survival, time to central nervous system (CNS) metastases at the time of first progression, incidence rates of CNS metastases at the time of progression, overall objective response rate, clinical benefit response rate, adverse-event profile, quality of life as measured by the EORTC Quality of Life Questionnaire Core 30 and a Trial Specific Checklist, clinical outcomes as measured by biomarker changes in biological samples, and economic evaluation, including health utilities, as measured by the EuroQuality of Life five-dimension questionnaire, and healthcare utilization. The estimated completion date for the 652-patient study is January 2014.

Sponsor: National Cancer Institute of Canada Clinical Trials Group Collaborator: GlaxoSmithKline

Prostate Cancer

ClinicalTrials.gov Identifier: NCT00667251Cabozantinib vs Prednisone for Metastatic Prostate Cancer

This phase III study will assess the effect of cabozantinib compared with prednisone on overall survival in men with previously treated metastatic castrationresistant prostate cancer with bone-dominant disease who have experienced disease progression on docetaxel-containing chemotherapy and abiraterone or MDV3100. The primary outcome measure is overall survival. The sole secondary outcome measure is bone scan response, which is being evaluated by an independent radiology facility. In order to be eligible, patients must have bone metastasis related to prostate cancer. Subjects will be randomized in a 2:1 ratio to receive cabozantinib or prednisone; each arm will also receive placebo in order to account for the once-daily versus twice-daily dosing regimens of cabozantinib and prednisone. The 960-patient trial is under way at 270 sites worldwide and has an estimated primary completion date of March 2014. In preclinical studies, cabozantinib has shown powerful tumoricidal, antimetastatic, and antiangiogenic effects, including extensive apoptosis of malignant cells, decreased tumor invasiveness and metastasis, decreased tumor and endothelial cell proliferation, blockade of metastatic bone lesion progression, and disruption of tumor vasculature.

Sponsor: Exelixis

ClinicalTrials.gov Identifier: NCT01605227

BIND-014 as First-Line Therapy for Metastatic Prostate Cancer

This phase II study is assessing the efficacy of BIND- 014 as measured by radiographic progression-free survival in roughly 40 patients with chemotherapynaïve, metastatic castration-resistant prostate cancer. The investigators will also examine safety and tolerability. The study is being conducted at six US sites and has an estimated primary completion date of August 2014. BIND-014 is a docetaxel-containing nanoparticle that targets prostate-specific membrane antigen, a target expressed on prostate cancer cells and the blood vessels of many types of non-prostate solid tumors, and contains the widely used chemotherapy drug docetaxel.

Sponsor: BIND Therapeutics

Brain Cancer

ClinicalTrials.gov Identifier: NCT01812746Dendritic Cell Immunotherapy for Brain Cancer

This phase III study is evaluating the use of DCVax®-L, autologous dendritic cells pulsed with tumor lysate antigen for the treatment of newly diagnosed unilateral glioblastoma multiforme in patients for whom surgery, radiation, and concurrent chemotherapy are indicated. All tests and eligibility criteria must be completed within 4 weeks of the completion of radiation and chemotherapy, following surgery. Patients must also have no evidence of disease progression after completion of radiotherapy. The primary outcome measure is progression-free survival. Secondary outcome measures include overall survival, safety, and the induction of immune responses. Target enrollment is 300 patients recruited from about 50 sites in the United States and internationally, and the estimated primary completion date is September 2014.

Sponsor: Northwest Biotherapeutics

ClinicalTrials.gov Identifier: NCT00045968

Bevacizumab With or Without Routine Care for Glioblastoma

This phase III study will evaluate the efficacy and safety of standard of care with or without continuous bevacizumab treatment following disease progression after first-line treatment in patients with glioblastoma. Newly diagnosed patients with glioblastoma will receive first-line treatment with radiotherapy, temozolomide, and bevacizumab (5 mg/kg/ week intravenously every 2 or 3 weeks). At disease progression, eligible patients will be randomized to receive a standard-of-care agent plus either bevacizumab (5 mg/kg/week given intravenously every 2 or 3 weeks) or placebo for second- and third-line treatment. The primary outcome measure is overall survival. Secondary outcome measures include second- line progression-free survival (PFS), third-line PFS, response rates, disease control rates, duration of response, safety, health-related quality of life, neurocognitive function tests, and resource utilization. The target recruitment is about 510 patients.

Sponsor: Hoffmann-La Roche

Renal Cancer

ClinicalTrials.gov Identifier: NCT01860638Dendritic Cell Immunotherapy for Advanced Renal Cancer

This phase III study will test the use of autologous dendritic cell immunotherapy (AGS-003) plus standard treatment in patients with advanced renal cell carcinoma (RCC). The primary outcome measure is overall survival. Secondary outcome measures include progression-free survival, tumor response, and treatment-emergent adverse events. Subjects must have advanced disease that is histologically assessed as RCC, with a component of clear-cell histology and measurable metastatic disease that can be monitored throughout the study by RECIST 1.1. Exclusion criteria include prior systemic therapy (including adjuvant or neoadjuvant) of any kind for RCC, including immunotherapy, chemotherapy, hormonal, or investigational therapy as well as individuals with a prior history of malignancy other than RCC within the preceding three years, except for adequately treated in situ carcinomas or nonmelanoma skin cancer. The investigators aim to recruit approximately 450 patients at 93 sites in the United States, Canada, and Israel.

Sponsor: Argos Therapeutics

ClinicalTrials.gov Identifier: NCT01582672

Bevacizumab Added to Interferon Alfa-2b for Advanced Renal Cell Cancer

This phase III trial is comparing interferon alfa-2b and bevacizumab versus interferon alfa-2b alone for the treatment of advanced renal cell carcinoma (RCC). After stratification by prior nephrectomy (yes vs no) and the number of risk factors for disease progression (0 vs 1-2 vs 3 or more), patients are randomized to one of two treatment arms. Individuals in Arm 1 will receive interferon alfa-2b subcutaneously three times a week, while those in Arm 2 will receive interferon alfa-2b plus intravenous bevacizumab over 30-90 minutes on days 1 and 15. In both arms, courses are repeated every 28 days in the absence of disease progression or unacceptable toxicity. Study participants are followed every 3 months for 2 years, and then annually for up to 10 years. The study includes about 700 patients.

Sponsor: Cancer and Leukemia Group B

Collaborators: National Cancer Institute, NCIC Clinical Trials Group, Eastern Cooperative Oncology Group

Gastrointestinal Cancer

ClinicalTrials.gov Identifier: NCT00072046Immunotherapy for Pancreatic Cancer

This phase III study will evaluate treatment with standard of care FOLFIRINOX with or without algenpantucel- L immunotherapy in patients with borderline resectable or locally advanced unresectable pancreatic cancer. The primary outcome measure is overall survival. Secondary outcome measures include progression-free survival, frequency and grade of adverse events, safety, and immune response. The researchers aim to recruit about 280 patients from eight US sites, with an estimated primary completion date of September 2015.

Sponsor: NewLink Genetics Corporation

ClinicalTrials.gov Identifier: NCT01836432

Adjuvant Erlotinib and Chemoradiation for Resected Pancreatic Cancer

This phase III study will compare gemcitabine with or without erlotinib followed by the same chemotherapy regimen with or without radiation therapy and capecitabine or fluorouracil for treating patients with resected pancreatic cancer. The primary outcome measure is overall survival. Secondary outcome measures include disease-free survival, adverse events assessed according to NCI Common Terminology Criteria for Adverse Events version 4.0, and the frequency of objective criteria of resectability as measured by preoperative imaging. About 950 patients will be enrolled. The target completion date is August 2020.

Sponsor: National Cancer Institute

Multiple Myeloma

ClinicalTrials.gov Identifier: NCT01013649Aplidin-Dexamethasone in Relapsed/Refractory Myeloma (ADMYRE)

This randomized, multicenter, open-label, phase III study will evaluate plitidepsin in combination with dexamethasone vs dexamethasone alone in patients with relapsed/refractory multiple myeloma. Plitidepsin, which induces cell death through various cellular pathways, was originally isolated from a marine organism known as a sea squirt. The primary outcome measure is progression-free survival as per intention-to-treat (ITT). Secondary outcome measures include response rate, duration of response, and overall survival. Approximately 250 patients will be enrolled. The target completion date is June 2014.

Sponsor: PharmaMar

ClinicalTrials.gov Identifier: NCT01102426

Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Newly Diagnosed, Previously Untreated Multiple Myeloma (ELOQUENT-1)

This phase III, randomized, open-label trial will compare lenalidomide/dexamethasone with or without elotuzumab in subjects with previously untreated multiple myeloma. Elotuzumab is a humanized monoclonal antibody that binds to the cell surface glycoprotein CA1. The cell surface protein is found primarily on myeloma cells (not on normal bone marrow cells). The primary outcome measure is progression- free survival. Secondary outcome measures include objective response rate and overall survival. Approximately 750 patients will be enrolled. The target completion date (final data collection date for primary outcome measure) is May 2016.

Sponsor: Bristol-Myers Squibb

ClinicalTrials.gov Identifier: NCT01335399