The Trials in Progress section is intended to stimulate discussion about ongoing clinical trials and to promote collaboration across the oncology community. Each month, OBTN will present summaries of ongoing research in a broad range of cancer types.

Brain Cancer

Donepezil for neurocognitive symptoms in irradiated brain tumor patients

This phase III study will compare the effects of the reversible acetylcholinesterase inhibitor donepezil versus placebo for improving neurocognitive symptom cluster in patients who have undergone partial- or whole-brain irradiation for brain tumors. Donepezil is approved for the treatment of mild to moderate Alzheimer’s-type dementia. Subjects will be randomized to donepezil or placebo once or twice daily for up to 24 weeks in the absence of unacceptable toxicity. The primary outcome measures are fatigue, subjective confusion, and cognitive performance at 24 weeks. The researchers will also compare the effects of these regimens on mood and quality of life.

Sponsor: Wake Forest University

ClinicalTrials.gov Identifier: NCT00369785

Sarcoma

TH-302 with doxorubicin or solo doxorubicin in soft-tissue sarcoma

This phase III study will determine whether the hypoxiaactivated prodrug TH-302 in combination with doxorubicin is a safe and effective treatment for patients with locally advanced unresectable or metastatic soft-tissue sarcoma who have not received prior chemotherapy. Eligible patients are required to have a pathologically confirmed diagnosis of soft-tissue sarcoma of the following histopathologic types: synovial sarcoma, high-grade fibrosarcoma, undifferentiated sarcoma or sarcoma not otherwise specified, liposarcoma, leiomyosarcoma (excluding gastrointestinal stromal tumor), angiosarcoma (excluding Kaposi’s sarcoma), malignant peripheral nerve sheath tumor, pleomorphic rhabdomyosarcoma, myxofibrosarcoma, epithelioid sarcoma, or undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (including pleomorphic, giant cell, myxoid, and inflammatory forms). Study participants will be randomized to treatment with TH-302 with doxorubicin or doxorubicin alone. The primary outcome measure is overall survival. The study aims to recruit about 450 patients, with a completion date in early 2015.

Sponsor: Threshold Pharmaceuticals

ClinicalTrials.gov Identifier: NCT01440088

Head and Neck Cancer

Efficacy of Reolysin with paclitaxel and carboplatin in platinum-refractory head and neck cancer

This phase III study is comparing intravenous administration of Reolysin (Reovirus Type 3 Dearing) combined with paclitaxel and carboplatin or chemotherapy treattreatment alone in patients with metastatic or recurrent squamous cell carcinoma of the head and neck who have progressed on or after prior platinum-based chemotherapy. Reolysin is an unmodified oncolytic reovirus that selectively replicates in Ras-activated cancer cells while not causing any significant human illness in its wild form. The primary outcome measure is overall survival. Patients will be evaluated clinically after each treatment course and radiologically every 6 weeks during and after treatment. The safety of the paclitaxel and carboplatin with intravenous blinded placebo or intravenous blinded Reolysin will also be assessed. The study aims to recruit 280 patients.

Sponsor: Oncolytics Biotech

ClinicalTrials.gov Identifier: NCT01166542

Management of chronic dry mouth in radiation-treated head and neck cancer

This phase II/III study is comparing acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) versus pilocarpine for treating xerostomia in patients undergoing radiation therapy for head and neck cancer in a cooperative group setting. Subjects are randomized to undergo either electrode placement at several acupuncture points followed by ALTENS to each of these points twice weekly for 20 minutes or oral pilocarpine 3 times daily. Treatment is continued for up to 12 weeks in the absence of disease progression or unacceptable toxicity. The primary outcome measures include successful delivery of ALTENS using the Codetron unit (phase II) and overall xerostomia burden at 9 months after randomization as measured by an established xerostomia-related quality-of-life scale (phase III). Overall, 45 patients will be accrued to the phase II portion and 144 patients to the phase III portion of the study.

Sponsor: Radiation Therapy Oncology Group

ClinicalTrials.gov Identifier: NCT00656513

Hematologic Cancer

Lenalidomide and dexamethasone with or without bortezomib in multiple myeloma

This phase III study will determine the efficacy of lenalidomide and low-dose dexamethasone with or without bortezomib for induction in patients with previously untreated multiple myeloma. Patients are stratified according to the International Staging System and intent to undergo transplantation at relapse. The primary outcome measure is progression-free survival. Secondary outcome measures include response rates, overall survival, and the correlation of genetic polymorphisms with biology and prognosis. In both arms, patients who intend to undergo transplantation at relapse undergo peripheral blood stem cell collection, preferably after course 2. The study has an estimated enrollment of 440 patients.

Sponsor: Southwest Oncology Group

ClinicalTrials.gov Identifier: NCT00644228

Rituximab and combination chemotherapy for diffuse large B-cell non-Hodgkin lymphoma

This phase III study will compare R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in patients with previously untreated, histologically confirmed-de novo diffuse large B-cell non-Hodgkin lymphoma. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years. The primary outcome measure is event-free survival 5 years after completion of study treatment. Secondary outcome measures include R-CHOP and doseadjusted- EPOCH-R molecular predictors of outcome as measured by cDNA microarray 5 years after completion of study treatment. A total of 478 patients will be recruited for the study.

Sponsor: Cancer and Leukemia Group B

ClinicalTrials.gov Identifier: NCT00118209

Prostate Cancer

Zoledronic acid versus standard therapy for preventing bone breaks in prostate cancer

This phase III study will compare treatment with zoledronic acid or calcium and vitamin D alone in men who are receiving radiation therapy and long-term LHRH agonists for high-grade and/or locally advanced prostate cancer. Subjects are maintained on treatment for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity. The primary outcome measure is freedom from any bone fracture. Secondary outcome measures include the percent change in bone mineral density at 3 years, changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General questionnaire, and the usefulness of bisphosphonates as assessed by the European Questionnaire- 5 Dimensional changes in quality-of-life scale questionnaire. The study plans to enroll 1272 patients.

Sponsor: Radiation Therapy Oncology Group

ClinicalTrials.gov Identifier: NCT00329797

Oral MDV3100 in chemotherapy-naïve patients with metastatic prostate cancer

This phase III study will test the efficacy and safety of the novel androgen signaling inhibitor MDV3100 in chemotherapy- naïve patients who have progressive metastatic prostate cancer despite androgen-deprivation therapy (ADT) as defined by rising prostate-specific antigen levels or progressive soft tissue or bony disease. Study participants are asymptomatic or mildly symptomatic from prostate cancer. The primary outcome measures are overall survival and progression-free survival. Secondary outcome measures are time to first skeletal-related event and time to initiation of cytotoxic chemotherapy. An estimated 1680 men will participate in the study, which has a targeted primary completion date of September 2014.

Sponsor: Medivation, Inc

ClinicalTrials.gov Identifier: NCT01212991