October 2012: Trials in Progress

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.

Ovarian Cancer

Solo ipilimumab for recurrent platinum-sensitive ovarian cancer

This phase II study will examine the use of ipilimumab monotherapy after completion of chemotherapy in recurrent platinum-sensitive ovarian cancer patients with an ECOG performance status of 0 or 1 and residual measurable disease. The primary outcome measure is the incidence of drug-related adverse events of grade 3 or higher during the induction period of ipilimumab. An intravenous solution of 10 mg/kg of ipilimumab will be administered once every 3 weeks for 4 doses, and then once every 12 weeks starting at week 24 until the onset of disease progression or unacceptable toxicity. The estimated enrollment is 40 patients. Women who have platinum-refractory ovarian cancer or who have had more than four lines of prior therapy are ineligible.

Sponsor: Bristol-Myers Squibb

ClinicalTrials.gov Identifier: NCT01611558

MM-121 plus paclitaxel in platinum-resistant/refractory advanced ovarian cancer

This phase II study will compare MM-121 combined with paclitaxel versus paclitaxel alone in patients with locally advanced/ metastatic or recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have received at least one prior platinum-based chemotherapy regimen and are platinum-resistant/refractory. For inclusion, patients must also be eligible for weekly paclitaxel. MM-121 is an investigational fully human monoclonal antibody that targets the ErbB3 receptor. The primary outcome measure is progression-free survival (PFS). The investigators aim to recruit about 210 women and hope to complete their study by April 2015.

Sponsor: Merrimack Pharmaceuticals

ClinicalTrials.gov Identifier: NCT01447706

Skin Cancer

T-VEC versus GM-CSF for advanced melanoma

This phase III study will compare talimogene laherparepvec (T-VEC) versus subcutaneous GM-CSF for the treatment of patients with unresectable stage IIIb, IIIc, and IV melanoma stratified by typical prognostic factors. T-VEC is an oncolytic HSV1 that selectively replicates in tumors with a proposed mechanism of action involving lytic destruction of injected tumors and induction of a systemic antitumor immune response enhanced by local GM-CSF expression. Patients will be randomized in a 2:1 ratio to T-VEC (priming dose of up to 4 x 106 pfu intratumorally, then 3 weeks later by up to 4 x 108 pfu every 2 weeks) or GM-CSF subcutaneously 125 μg/m2 daily for 14 days every 28 days. Study participants must have ECOG status of 0-1 and at least one injectable cutaneous, subcutaneous, or nodal tumor. The primary endpoint is durable response rate, defined as a complete or partial response continuously maintained for at least 6 months that started within 12 months of treatment initiation. The sole secondary endpoint is overall survival (OS).

Sponsor: Amgen

ClinicalTrials.gov Identifier: NCT00769704

Sulforaphane for atypical nevi precursor lesions

This study will evaluate sulforaphane as a possible nutritional chemopreventive agent for modulating key steps in melanoma progression and the expression of signal transducer and activator of transcription proteins in melanocytic and stromal elements of atypical nevi. Sulforaphanes are bioactive cruciferous compounds rich in the Brassica family, especially broccoli sprouts; topical broccoli sprout extracts reduce ultraviolet radiation (UVR) erythema response in human skin, and may protect against UVR DNA damage. Melanoma patients with more than two atypical nevi will receive oral broccoli sprout extract rich in sulforaphane at dosages of 50 μmol, 100 μmol, or 200 μmol daily for 28 days. Subjects must avoid dietary glucosinolates and isothiocyanates throughout the study and maintain food diaries. Blood samples, photography of index atypical nevi, and biopsies of selected atypical nevi and normal skin will be analyzed for changes in atypia, sulforaphane localization histopathology, and STAT 1/3 expression in the nevi and skin harvested at baseline and at study completion.

Sponsor: John Kirkwood, MD, University of Pittsburgh

ClinicalTrials.gov Identifier: NCT01568996

Breast Cancer

Denosumab as adjuvant treatment for high-risk, early-stage breast cancer

This phase III study will compare denosumab versus placebo as adjuvant treatment for women with stage II or III breast cancer who are at high risk of disease recurrence, and whose hormone and HER2 receptor status is known. Study participants must be scheduled for standard-of-care adjuvant or neoadjuvant chemotherapy, endocrine, or HER2 targeted therapy to be administered alone or in combination. Patients will be randomized to receive 120 mg of denosumab or placebo subcutaneously monthly for 6 months, and then every 3 months, for a total of 5 years of treatment, along with vitamin D and calcium supplementation. The primary endpoint of the study is bone metastasis—free survival. Secondary endpoints include OS and distant recurrence–free survival. Investigators will also examine disease-free survival, as well as safety and tolerability.

Sponsor: Amgen, Daiichi Sankyo

ClinicalTrials.gov Identifier: NCT01077154

Aromatase inhibitor combined with lapatinib or trastuzumab or both for metastatic breast cancer

This phase III study will randomize postmenopausal women with metastatic breast cancer to one of three treatment arms as first-line therapy: lapatinib plus trastuzumab plus an aromatase inhibitor (AI); trastuzumab plus an AI; or lapatinib plus an AI. Study participants must have HER2+/HR+ metastatic breast cancer and have received trastuzumab and endocrine therapy in the neoadjuvant and/or adjuvant setting, but must be ineligible for chemotherapy. The AI can be letrozole, anastrozole, or exemestane, with the choice of treatment made by the investigator. The primary efficacy endpoint is OS for lapatinib/ trastuzumab/AI versus trastuzumab/AI. Secondary efficacy measures include a comparison of OS between trastuzumab/ AI and lapatinib/AI, as well as between trastuzumab/ lapatinib/AI and lapatinib/AI; comparisons of PFS, overall response rate (ORR); time to response; duration of response; and safety and tolerability for all three treatment groups.

Sponsor: GlaxoSmithKline

ClinicalTrials.gov Identifier: NCT01160211

Prostate Cancer

Orteronel for advanced prostate cancer

This phase III study will compare the investigational agent orteronel (TAK-700) plus prednisone versus placebo plus prednisone in patients with mCRPC that has progressed during or following docetaxel-based therapy. Orteronel is a selective inhibitor of 17,20-lyase, a key enzyme in the testosterone synthesis pathway. In order to be eligible, patients must have evidence of disease progression during or after receiving a total of 360 mg/m2 docetaxel or more within a 6-month period. Patients who cannot tolerate docetaxel or who have progressive disease before receiving 360 mg/m2 or more are also eligible if they have received at least 225 mg/m2 of docetaxel within a 6-month period and satisfy the other inclusion criteria, which include radiographically documented metastatic disease and baseline testosterone level lower than 50 ng/dL following surgical or medical castration. The primary endpoint is OS. Secondary endpoints include radiographic PFS, PSA decrease of ≥50% at 12 weeks, pain response at 12 weeks, safety, time to PSA progression, ORR by RECIST, circulating tumor cell and endocrine marker changes, and patient-reported outcomes. Tumor specimens will be analyzed for biomarkers that may predict orteronel antitumor activity.

Sponsor: Millennium Pharmaceuticals

ClinicalTrials.gov Identifier: NCT01193257

Sarcoma

Trabectedin- or doxorubicin-based chemotherapy for translocation-related sarcoma

This phase III study will compare trabectedin versus standard doxorubicin-based chemotherapy as first-line treatment in patients with advanced translocation-related sarcoma (TRS). Trabectedin is the first of a new class of antitumor agents with a transcription-targeted mechanism of action. Patients with confirmed TRS of several subtypes, including myxoid/round-cell liposarcoma, alveolar soft-part sarcoma, angiomatoid fibrous histiocytoma, clear-cell sarcoma, desmoplastic small round-cell tumor, low-grade endometrial stromal sarcoma, low-grade fibromyxoid sarcoma, myxoid chondrosarcoma, and synovial sarcoma, are stratified by performance status and sarcoma subtype and randomized to trabectedin or doxorubicin with or without ifosfamide. Confirmation of the translocation by fluorescence in situ hybridization is required for inclusion in the primary efficacy analysis. The primary outcome measure is PFS. Secondary outcome measures include best objective response, OS, duration of response, and incidence of adverse events.

Sponsor: Johnson & Johnson

ClinicalTrials.gov Identifier: NCT00796120