November 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. This month’s collection highlights trials presented at the 2011 American Society of Clinical Oncology Meeting [J Clin Oncol. 2011;29(suppl)].

Breast Cancer

Evaluating role of CER into RxPONDER study

The Center for Comparative Effectiveness Research in Cancer Genomics (CANCERGEN) is designed to integrate comparative effectiveness research (CER) into prospective SWOG (formerly Southwestern Oncology Group) trials. This is being applied to the RxPONDER study, a prospective randomized trial evaluating the role of Oncotype DX-guided therapy compared to usual care among women with lymph node-positive, endocrineresponsive breast cancer. Women with endocrineresponsive HER2-negative breast cancer involving 1 to 3 lymph nodes are invited to receive a test based on the 21-gene assay. Those with a recurrence score (RS) ≤25 are randomized into chemotherapy followed by endocrine therapy or endocrine therapy alone. In addition to RxPONDER primary endpoints, economic modeling and trial data will be used to assess the cost effectiveness of management using RS compared to usual care. Abstract TPS101.

Sponsor: SWOG

ClinicalTrials.gov Identifier: NCT01272037

Dual IGF-1R/IR inhibitor with or without letrozole in aromatase inhibitor-resistant breast cancer

Evidence shows that insulin-like growth factor (IGF) pathway signaling contributes to tamoxifen resistance, and blocking that signaling may reverse resistance to endocrine therapy. A phase II trial is underway to investigate the combination of BMS-754807, an oral IGF-1R/insulin receptor (IR) kinase inhibitor, and 2.5 mg letrozole or single-agent BMS-754807 in patients with locally advanced or metastatic, estrogen receptor-positive, nonsteroidal aromatase inhibitorresistant breast cancer. The primary objective is 6-month progression-free survival (PFS) for the combination. Secondary endpoints include response rate, safety profile, and 6-month treatment failure rate for BMS-754807 and for the combination. Abstract TPS111.

Sponsor: Bristol-Myers Squibb and National Institutes of Health

ClinicalTrials.gov Identifier: NCT01225172

Gastrointestinal Cancer

PARP inhibitor for use in patients with metastatic pancreatic cancer

Poly (ADP-ribose) polymerase (PARP) inhibitors are sensitizing agents for DNA-damaging chemotherapy agents like platinum analogs, and the effects are magnified when cancer cells harbor DNA repair enzyme defects, including BRCA2, FANCD2, PTEN, and others. An open-label phase I/II study has been initiated to study a PARP inhibitor called ABT-888 in patients with metastatic, unresectable pancreatic cancer who have adequate performance status and normal hepatic and renal function. The primary endpoint is to achieve objective response rate (ORR). Secondary endpoints include disease control rate, PFS, and overall survival (OS). Abstract TPS170.

Second-line therapy with PIE in metastatic colorectal cancer with KRAS wild-type

Activation of the EGFR results in cell proliferation and survival. Mutations in the KRAS gene result in an active protein that is independent of EGFR and is not inhibited by anti-EGFR monoclonal antibodies. Aberrations in other downstream signaling also confer resistance to EGFR antagonists. Inhibition of the mammalian target of rapamycin (mTOR), a key downstream regulatory protein, in addition to the blockage of EGRF, may cause a more profound antitumor effect. A study is enrolling patients with metastatic colorectal cancer that is KRAS wild-type. Patients received panitumumab and irinotecan through IV every 2 weeks, with everolimus administered orally throughout the 14-day cycle. Abstract TPS162.

Sponsor: The Queen Elizabeth Hospital, Amgen, Novartis

ClinicalTrials.gov Identifier: NCT01139138

Genitourinary Cancer

Vascular-disruption agent in combination with everolimus for progressive renal cell carcinoma

Treatment of progressive metastatic renal cell carcinoma (mRCC) for patients who are refractory to tyrosine kinase inhibitors (TKIs) with everolimus following previous sunitinib and/or sorafenib has been associated with significant improvement in PFS. Vascular-disruption agents (VDAs) may provide potential enhancement in efficacy by acting to damage tumor endothelial cells, leading to an occlusion of blood flow and subsequent necrosis. BNC105P is a VDA that destabilizes tubulin polymers leading to a direct antiproliferative action on cancer cells. The phase I component of this study will investigate BNC105P at 4 dose levels and everolimus in the approved dosage. The phase II study will compare everolimus with BNC105P to everolimus alone. Abstract TPS194.

Sponsor: Hoosier Oncology Group, Bionomics Limited

ClinicalTrials.gov Identifier: NCT01034631

Hematologic Cancer

Registry of branded imatinib and nilotinib exposure in pregnant women explored

Sponsor: Novartis Pharmaceuticals

ClinicalTrials.gov Identifier: NCT01289054

Family planning decisions, especially those regarding pregnancy, can be impacted by a cancer diagnosis. Imatinib and nilotinib are category D drugs, and their benefit to the patient may outweigh the risks to a developing fetus in pregnant women. A registry is being designed to explore what happens when women who are taking the drugs become pregnant. The registry intends to enroll 225 women aged ≥18 years treated with branded-only imatinib and nilotinib within 6 months prior to or during pregnancy. The women are divided into 2 groups. The first group will include those who received a TKI within 14 days of conception or anytime during pregnancy, and the second group will include women who received TKIs within 6 months prior to pregnancy but halted taking them as a result of pregnancy. Abstract TPS205.

Phase III study of panobinostat in patients with relapsed multiple myeloma

Sponsor: Novartis Pharmaceuticals

ClinicalTrials.gov Identifier: NCT01023308

Panobinostat (PAN) is an oral pan-deacetylase inhibitor (pan-DACi) with synergistic antimyeloma activity in combination with bortezomib (BTZ), which may occur through dual inhibition of DACs and the proteasome. A global, randomized, double-blind phase III study of PAN plus BTZ plus dexamethasone (DEX) compared to placebo with BTZ and DEX has been initiated to determine if PAN can improve outcomes in patients with multiple myeloma. Patients with relapsed or relapsed and refractory multiple myeloma who have had 1 to 3 prior lines of therapy will be enrolled. The primary endpoint is PFS, and the key secondary endpoint is OS. Abstract TPS227.

Women’s Cancer

Catumaxomab in patients with epithelial ovarian cancer

Patients with epithelial ovarian cancer in second or third complete remission have minimal residual disease that causes recurrence in almost every patient. A phase II study is being conducted to estimate the clinical benefit of treating these patients with the antibody catumaxomab, which has been proven to be effective in patients with refractory tumors. Patients are treated for 11 days, with a follow-up of 28 days after the last dose of catumaxomab and subsequent follow-up every 3 months until disease progression. The planned enrollment for the trial is 35 assessable patients. In addition to the clinical benefit of catumaxomab, secondary endpoints are safety, compliance, treatmentfree interval, and OS. Abstract TPS195.

Sponsor: Fresenius Biotech GmbH

ClinicalTrials.gov Identifier: NCT01246440