Trials in Progress Poster Session

The Trials in Progress Poster Session (TPS) at the ASCO Annual Meeting, now in its third year, is intended to stimulate discussion in the oncology community about ongoing clinical trials and to promote collaboration. The following is a roundup of TPS abstracts covering a broad range of cancer types.

Prostate Cancer

Cabazitaxel versus standard treatment for metastatic castration-resistant prostate cancer

This phase III study will test whether first-line cabazitaxel in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) is superior to docetaxel (D). Both treatment groups will receive concurrent prednisone. Cabazitaxel is a novel taxane active in D-sensitive and D-resistant tumor models. Docetaxel/prednisone as first-line chemotherapy in patients with mCRPC is the current standard of care; however, treatment is not curative, and D-resistant disease typically develops. Patients with ECOG performance status of 0-2, histologically/cytologically confirmed metastatic prostate adenocarcinoma with no prior chemotherapy and with disease progression following medical or surgical castration are eligible. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival (PFS), radiologic PFS, tumor response in measurable disease, prostate-specific antigen (PSA) response and PSA PFS, pain response and pain PFS, time to occurrence of any skeletal-related events, safety profile, and health-related quality of life. Cabazitaxel pharmacokinetics and pharmacogenomics will be assessed in patient subgroups. Abstract TPS4696.

Sponsor: Sanofi

ClinicalTrials.gov Identifier: NCT01308567

Neoadjuvant MDV3100 for prostate cancer

This phase II study will test the effect of neoadjuvant androgen receptor (AR) blockade with AR inhibition alone using MDV3100 or combined with maximal suppression of androgens involving MDV3100 plus leuprolide and dutasteride. MDV3100 is a potent AR-signaling inhibitor that inhibits AR signaling via three mechanisms: inhibition of androgen binding to AR, inhibition of AR nuclear translocation, and inhibition of nuclear AR-DNA binding. The study population includes men with treatment-naïve, localized prostate cancer who are candidates for radical prostatectomy and have either a PSA greater than 10 ng/mL or Gleason score of 7 (4 + 3) or higher with 3 or more cores containing tumor and no evidence of metastatic/nodal disease. All patients receive MDV3100 (160 mg/day orally); those randomized to MDV3100 plus leuprolide and dutasteride therapy also receive leuprolide (22.5 mg IM every 3 months) and dutasteride (0.5 mg/day orally). The primary efficacy endpoint is pathological complete response rate at the time of radical prostatectomy. Abstract TPS4695.

Sponsor: Medivation; Astellas Pharma

ClinicalTrials.gov Identifier: NCT01547299

Brain Cancer

ICT‑107 for glioblastoma multiforme after resection and chemoradiation

This phase II study will test the efficacy and safety of ICT-107 in patients with newly diagnosed glioblastoma multiforme (GBM) who have undergone complete surgical resection or have minimal residual tumor <1 cm3, and are HLA-A1— and/or HLA-A2–positive. In order to be eligible for enrollment, patients must also have a Karnofsky performance status ≥70% and adequate hematologic and chemistry parameters. ICT‑107 is an autologous vaccine consisting of the patient’s dendritic cells pulsed with six synthetic peptide CTL epitopes targeting the GBM tumor and tumor stem cell–associated antigens MAGE‑1, HER2, AIM‑2, TRP‑2, gp100, and IL‑13Rα2. The primary endpoint is OS. Secondary endpoints include PFS, rates of OS and PFS at 6 months after surgery and every 3 months thereafter, safety and tolerability of ICT‑107, immune response to ICT-107, and predictors of response. Approximately 200 patients are expected to be enrolled for screening. Abstract TPS2107.

Sponsor: ImmunoCellular Therapeutics, Ltd.

ClinicalTrials.gov Identifier: NCT01280552

Breast Cancer

Afatinib or trastuzumab with vinorelbine for metastatic breast cancer

This phase III study will compare afatinib plus vinorelbine versus trastuzumab plus vinorelbine in women with HER2-overexpressing metastatic breast cancer who progressed on or after one prior trastuzumab-based treatment regimen. Afatinib is an ErbB family blocker that irreversibly blocks signaling from all relevant ErbB family dimers. Patients will be randomized in a 2:1 ratio to afatinib (40 mg/day PO) plus vinorelbine (IV 25 mg/m²/week) or trastuzumab (IV 2 mg/kg/week after 4 mg/ kg-loading dose) plus vinorelbine (IV 25 mg/m²/week) and will be treated continuously until the onset of disease progression or adverse events. The primary endpoint is PFS. Secondary endpoints include best RECIST assessment, OS, tumor shrinkage, time to deterioration, and safety. The investigators will assess serum and tissue biomarkers and HER-receptor and HER-ligand reprogramming, putative resistance markers, and EGFR response signature. Abstract TPS649.

Sponsor: Boehringer Ingelheim Pharmaceuticals

ClinicalTrials.gov Identifier: NCT01125566

Gastrointestinal Cancer

Bevacizumab tested as add-on to standard treatment for gastrointestinal cancer

This phase II/III study will test the safety, feasibility, and efficacy of the addition of bevacizumab to perioperative epirubin, cisplatin, and capecitabine (ECX) chemotherapy in patients with operable esophagogastric adenocarcinoma. Perioperative ECX chemotherapy is a standard of care for localized gastric/esophagogastric junction/lower esophageal adenocarcinoma. Surgery is prespecified, and laparoscopic procedures are permitted only after a quality assurance review. The primary outcome measures for stage I, which include safety data, have been reported. The stage II primary outcome measures are safety, efficacy, and OS. Secondary outcome measures are feasibility, treatment-related morbidity, response rates to preoperative treatment, surgical resection rates, disease-free survival (DFS), quality of life, and cost-effectiveness. Abstract TPS4143.

Sponsor: Professor David Cunningham/Medical Research Council and Cancer Research UK

ClinicalTrials.gov Identifier: NCT00450203

Paclitaxel with or without ramucirumab for advanced gastric cancer

This phase III study will compare paclitaxel with or without the investigational agent ramucirumab in patients with metastatic gastric adenocarcinoma that was refractory to or progressed after first-line therapy with platinum and fluoropyrimidine. Ramucirumab is a fully human monoclonal antibody that binds to VEGFR-2, potently blocks the binding of VEGF to VEGFR-2, inhibits VEGF-stimulated activation of VEGFR-2, and neutralizes VEGF-induced mitogenesis of human endothelial cells. Study participants will be randomized to receive ramucirumab plus paclitaxel or placebo plus paclitaxel until disease progression or intolerable toxicity, administered in a 28-day cycle with ramucirumab or placebo 8 mg/kg on days 1 and 15, and paclitaxel 80 mg/m² on days 1, 8, and 15. The primary endpoint is OS. Secondary endpoints include PFS, time to progression, best overall response, objective response rate, safety, patient-reported outcome measures, pharma- codynamics, immunogenicity, and pharmacokinetics. Abstract TPS4139.

Sponsor: ImClone LLC

ClinicalTrials.gov Identifier: NCT01170663

Ganitumab or placebo plus gemcitabine for metastatic pancreatic cancer

This phase III study will compare ganitumab (AMG 479) or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas. Ganitumab is an investigational, fully human monoclonal antibody antagonist of the insulin-like growth factor-1 receptor (IGF-1R). Study participants must have untreated metastatic adenocarcinoma of the pancreas, an ECOG status of 0-1, adequate organ function, and fasting or nonfasting glucose of 160 mg/dL or greater. Patients will be randomized in a 2:2:1 ratio to placebo plus gemcitabine, 12 mg/kg of ganitumab plus gemcitabine, or 20 mg/kg of ganitumab plus gemcitabine. They receive ganitumab or placebo IV on days 1 and 15 and 1000 mg/m² of gemcitabine IV on days 1, 8, and 15 every 28 days. Patients receiving 20 mg/kg of ganitumab are expected to achieve ganitumab levels above the median in phase II. The primary endpoint is OS. Secondary endpoints are PFS, objective response rate, time to disease progression, disease-control rate, and adverse events. Investigators will also aim to define a subpopulation with improved OS based upon baseline levels of circulating biomarkers. Abstract TPS4135.

Sponsor: Amgen Inc and Takeda

ClinicalTrials.gov Identifier: NCT01231347

Genitourinary Cancer

Adjuvant chemotherapy following chemoradiation for cervical cancer

This phase III study is aiming to determine whether the addition of adjuvant chemotherapy to standard cisplatin-based chemoradiation improves OS in women with locally advanced cervical cancer (FIGO stage IB₁ and node-positive, IB₂, II, IIIB or IVA). Women are randomized to either standard cisplatin-based chemoradiation or standard cisplatin-based chemoradiation followed by 4 cycles of carboplatin and paclitaxel chemotherapy. Secondary outcome measures include PFS, treatment-related toxicity, patterns of disease recurrence, quality of life including psychosexual health, and the association between radiation protocol compliance and outcomes. Blood and tumor samples will be obtained from consenting patients for future translational studies. Investigators aim to enroll 780 women for the 5-year study. Abstract TPS5116.

Sponsor: Gynecologic Oncology Group

ClinicalTrials.gov Identifier: NCT01414608

Everolimus alternating with sunitinib for renal cancer

This phase II study is aiming to determine the activity and safety of an alternating regimen of two therapies with different targets (sunitinib and everolimus) in patients with advanced renal cell carcinoma (RCC). Individuals are eligible provided they have RCC with a clear-cell component, metastatic or locally advanced disease not suitable for resection, ECOG performance status of 0-1, and low or intermediate Memorial Sloan-Kettering Cancer Center prognostic score. Treatment is administered in 12-week cycles consisting of 4 weeks of sunitinib (50 mg daily) followed by 2 weeks’ rest, followed by 5 weeks of everolimus (10 mg daily), followed by 1 week of rest. The primary endpoint is the status of being alive and progression-free by RECIST 1.1 criteria 6 months after enrollment. Participants who stop one drug because of toxicity or disease progression on or before the 6-month assessment will continue the other drug until subsequent progression or unacceptable toxicity on the second drug. Abstract TPS4681.

Sponsor: The University of Sydney; Novartis

Australian New Zealand Clinical Trials Registry Identifier: ACTRN12609000643279

Head and Neck Cancer

Radiotherapy and cisplatin or panitumumab for head and neck cancer

This phase III study will compare standard fractionation radiotherapy with concurrent high-dose cisplatin versus accelerated fractionation radiotherapy with panitumumab in patients with locally advanced stage III and IV squamous cell carcinoma of the head and neck (HNSCC). The study will enroll patients with SCC of the oral cavity, oropharynx, larynx, or hypopharynx; any T, N+, M0, or T3-4, N0, M0; and adequate organ function and performance status. After stratification by T category, nodal status, radiotherapy delivery modality, anatomic location, and participation in the optional swallowing impairment substudy, subjects will be randomized to one of two treatment arms. Patients assigned to arm I will undergo standard fractionation radiotherapy once daily, 5 days a week, for 7 weeks; they will also receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy. Patients assigned to arm II will undergo accelerated fractionation radiotherapy once or twice daily, 5 days a week, for 6 weeks; they will also receive panitumumab IV over 30-90 minutes 1 week prior to and on days 15 and 36 of radiotherapy. The primary endpoint is PFS. Secondary endpoints include OS, local and regional PFS, distant metastases, adverse events, swallowing-related quality of life, functional swallowing outcomes, and economic assessments. Abstract TPS5600.

Sponsor: NCIC Clinical Trials Group

ClinicalTrials.gov Identifier: NCT00820248

Afatinib versus placebo for head and neck cancer

This phase III study will compare afatinib versus placebo as adjuvant therapy in patients with HNSCC who have received definitive chemoradiotherapy. Patients are eligible provided they have received definitive chemoradiation to a minimum of 66 Gy, with concurrent cisplatin (≥200 mg/m²) or carboplatin (≥AUC 9), for SCC of the oral cavity, oropharynx, hypopharynx, or larynx. Patients are randomized within 16 weeks of the completion of chemoradiation with or without subsequent neck dissection in a 2:1 ratio to 40 mg of afatinib orally once daily or placebo. Treatment is continued for 18 months in the absence of disease recurrence, second primary tumors, or intolerance to the study medication. The afatinib dose is increased to 50 mg once daily in patients with no side effects, and a stepwise decrease in dosage to 30 or 20 mg once daily is permitted for diarrhea, skin toxicity, or other adverse events. The primary endpoint is DFS. Secondary endpoints are safety, DFS at 2 years, OS, health-related quality of life, and adverse events. Abstract TPS5599.

Sponsor: Boehringer Ingelheim Pharmaceuticals

ClinicalTrials.gov Identifier: NCT01345669

Hematologic Malignancies

Lenalidomide/dexamethasone with or without elotuzumab for previously untreated multiple myeloma

This phase III study is aiming to determine whether the addition of elotuzumab to lenalidomide/dexamethasone improves PFS in patients with newly diagnosed, untreated multiple myeloma (MM) who are ineligible for stem cell transplant. Elotuzumab is an investigational humanized, monoclonal Immunoglobulin G1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on more than 95% of MM cells. The primary endpoint of the 750-patient trial is PFS. Secondary endpoints are objective response rate and OS. The researchers will also assess safety, time to response, duration of response, time to subsequent therapy, health-related quality of life, the pharmacokinetics and immunogenicity of elotuzumab, and potential biomarkers. Abstract TPS8113.

Sponsor: Bristol-Myers Squibb; Abbott Biotherapeutics Corp

ClinicalTrials.gov Identifier: NCT01335399

Ovarian Cancer

Dendritic cell vaccine being tested for ovarian cancer patients in remission

This study will examine Cvac treatment of patients with epithelial ovarian cancer (EOC) who are in first remission after surgery and standard chemotherapy, with at least three cycles of platinum and taxane therapy. Cvac is an investigatioal autologous dendritic cell immune stimulant targeting mucin-1 positive tumors. Study endpoints include PFS, OS, safety evaluation, and quality of life scores. Patients are eligible if they have stage III or IV mucin-1 positive EOC and have had optimal cytoreductive surgery, defined as <1cm residual disease and remain eligible if they have a complete response to standard chemotherapy after surgery. Computed tomography or magnetic resonance imaging will be used to determine progression. Abstract TPS5113.

Sponsor: Prima BioMed

Ombrabulin plus carboplatin and paclitaxel in platinum-sensitive recurrent ovarian cancer

This phase II placebo-controlled randomized trial is examining the addition of the investigational treatment Ombrabulin (AVE8062) to carboplatin and paclitaxel in patients with measurable carcinoma of the ovarian epithelium, fallopian tube, or primary peritoneum. Ombrabulin targets tumor vasculature, causing tumor necrosis. The primary endpoint is PFS. Secondary endpoints include OS, analysis of predictive/prognostic biomarkers, response rate, safety, and pharmacokinetics. Eligible patients must have an ECOG performance status ≤2 and have received one prior line of platinum-based chemotherapy. Exclusion criteria include a history of cardiovascular disease, peripheral neuropathy >grade 1, and uncontrolled brain metastases. Thus far, 43% (65/150) of the trial’s planned enrollment has been reached. The trial is being conducted at approximately 50 international sites. Abstract TPS5112.

Sponsor: Sanofi

ClinicalTrials.gov Identifier: NCT01332656