December 2011: 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.

Breast Cancer

Evaluating trastuzumab/capecitabine and pertuzumab in patients whose cancer has progressed

Researchers are recruiting for the multicenter, randomized PHEREXA study. The phase II, 2-arm study will examine the safety and efficacy of giving pertuzumab and trastuzumab with capecitabine in women with HER2- positive metastatic breast cancer whose disease has progressed during or following trastuzumab therapy. As of January 2011, researchers have recruited 58 patients for this open-label trial, but they hope to recruit 450 patients from 19 countries. Patients in both arms will receive trastuzumab and capecitabine, while 1 arm will also receive pertuzumab. Progression-free survival (PFS) is the primary endpoint. Overall survival, PFS, safety, and tolerability are secondary endpoints. Researchers plan to analyze HER1, -2, and -3 receptor status and downstream markers.

Sponsor: Hoffmann-LaRoche

ClinicalTrials.gov Identifier: NCT01026142

Phase II study of iniparib in breast cancer that has metastasized

Researchers plan to recruit 40 patients with triple-negative breast cancer (TNBC), which has metastasized to the brain, to evaluate the safety and efficacy of iniparib plus irinotecan. TNBC patients with brain metastases experience poor survival rates. The researchers are accepting patients with brain metastases that measure more than 0.5 cm, even if they have already received therapy with iniparib or steroids. However, those with leptomeningeal disease will be excluded. Cohort 1 will be those with new and/or progressive brain metastases following radiation of the central nervous system (CNS). Cohort 2 will be asymptomatic patients who have not received CNS radiotherapy. Patients will receive irinotecan before iniparib. Researchers will use MRI and CT scans to determine the presence of intra- and extracranial disease. Time to progression is the primary endpoint. Secondary endpoints include CNS and non-CNS response rates, progression-free survival, overall survival, quality of life, and correlative science endpoints.

Sponsor: sanofi-aventis

ClinicalTrials.gov Identifier: NCT01173497

PARP inhibition among patients with TNBC

The Hoosier Oncology Group is conducting a multicenter, randomized, phase II trial of cisplatin alone or cisplatin with the experimental compound PF 01367338 among patients with triple-negative breast cancer (TNBC) who have not achieved pathologic complete response (pCR) on anthracyclineand/ or taxane-containing neoadjuvant chemotherapy. The 2-year disease-free survival (DFS) of TNBC patients with residual disease category II or III is poor,%u2015only about 40%. There are no standard systemic therapies for this high-risk group. The researchers chose cisplatin because of its DNA-damaging properties. Cisplatin and PF 01367338 appear to affect the PARP breast cancer cells; they inhibit the replication of DNA and their growth. After completing standard radiation therapy, patients will be randomized to cisplatin alone or with PF 01367338. The primary endpoint is 2-year DFS. Secondary endpoints include safety, 1-year DFS, overall survival, and biomarkers of tumor recurrence, resistance to chemotherapy and/or PARP inhibition. The estimated enrollment is 135 patients.

Sponsor: Hoosier Oncology Group and Pfizer

ClinicalTrials.gov Identifier: NCT01074970

Gastrointestinal Cancer

Phase II trial of FOLFOX with or without vismodegib in advanced gastrointestinal cancer

Researchers are recruiting for a multicenter, phase II study of FOLFOX with or without GDC-0449 (vismodegib) in treatment-naïve patients with advanced gastric and gastroesophageal (GE) junction carcinoma. This randomized, double-blind study will review the efficacy and safety of vismodegib plus FOLFOX versus FOLFOX alone as first-line treatment for advanced GE cancers. The hedgehog (Hh) pathway is critical in the development of both normal and malignant gastroesophageal cell growth and survival, but Hh overexpression correlates with clinical and histological features of GE tumors. Vismodegib, an oral Hh antagonist, binds to and inhibits SMO (Smoothened), a key component of the Hh pathway. By inhibiting SMO, Hh signal transduction is blocked. Patients will receive FOLFOX (leucovorin calcium, fluorouracil, oxaliplatin) with either vismodegib or placebo. Progression free survival is the primary endpoint. Secondary endpoints are overall survival, relative risk, and toxicity rates. The estimated enrollment is 116 patients. As of June 2011, the researchers had enrolled 58 patients.

Sponsor: New York Cancer Consortium and National Cancer Institute

ClinicalTrials.gov Identifier: NCT00982592

Genitourinary Cancer

PREDICT looking for predictive biomarkers in renal cell carcinoma

The PREDICT (Personalized RNA Interference to Enhance the Delivery of Individualized Cytotoxic and Targeted Therapeutics) Consortium is conducting multicenter, single-arm phase II trials of everolimus (E-PREDICT) or sunitinib (S-PREDICT) administered around the time of the nephrectomy in patients with untreated metastatic renal cell carcinoma (mRCC). Although inhibitors of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR) have transformed mRCC therapy, predictive biomarkers have not been identified. The researchers plan to analyze the molecular markers of paired biopsies before and after treatment and compare them to clinical data to find predictive biomarkers. Sunitinib and everolimus will be given before and after nephrectomy and will continue until disease progression at metastatic sites. The primary clinical endpoint is the safety of peri-nephrectomy everolimus and sunitinib. Secondary endpoints include efficacy and biomarker measurements. The researchers hope to recruit 60 patients per trial.

Sponsor: The PREDICT Consortium

Hematologic Cancer

Phase II study of nilotinib in Ph CML patients

Researchers are evaluating patients with Philadelphia chromosome-positive (Ph ) chronic myeloid leukemia in chronic phase (CML-CP) with low imatinib plasma concentrations to see if nilotinib will improve patient outcomes. Patients with low plasma concentrations of imatinib are at risk for treatment failure. Nilotinib is a second-generation Bcr-Abl tyrosine kinase inhibitor and has a higher affinity for Abl than imatinib. Researchers will enroll 50 patients with Ph CML-CP who have been diagnosed within the 12 months prior to recruitment and who meet other European LeukemiaNet (ELN) response milestones, but who still have a low plasma concentration of imatinib. The patients will be switched from imatinib to nilotinib and treated for up to 2 years. The primary endpoint is the number of ELN-defined failure events during the course of nilotinib therapy. Secondary endpoints include cytogenetic and molecular response, and event-free, progression-free, and overall survival. Changes in quality of life will also be considered.

Sponsor: Novartis Oncology

ClinicalTrials.gov Identifier: NCT01131325

Phase II study of elacytarabine/idarubicin as second-course remission-induction therapy in AML

Researchers are studying elacytarabine with idarubicin in patients with acute myeloid leukemia (AML), who have more than 5% remaining blasts in the bone marrow after the first induction course of a regimen containing cytarabine. The decreased expression of hENT1 (human equilibrative nucleoside transporter 1) has been shown to contribute to cytarabine resistance. Elacytarabine, with or without idarubicin, has shown activity in refractory or relapsed patients with AML during phase I studies with a safety profile similar to the cytarabine/idarubicin regimen. In this phase II, multicenter study, researchers will biopsy bone marrow to determine the hENT1 expression level prior to beginning the new protocol. The primary objectives are to assess the biological activity of elacytarabine/ idarubicin and to examine the correlation between hENT1 and overall survival.

Sponsor: Clavis Pharma, Theradex, INC Research

ClinicalTrials.gov Identifier: NCT01035502