PARP Inhibitor in Advanced Solid Tumour or B-Cell Malignancies VFinal

• Research type

  Research Study

• Full title

  An Open-Label, Multicenter, Phase 1/2 Study of Poly(ADP-Ribose) Polymerase (PARP) Inhibitor E7449 as Single Agent in Subjects with Advanced Solid Tumors or with B-cell Malignancies and in Combination with Temozolomide (TMZ) or with Carboplatin and Paclitaxel in Subjects with Advanced Solid Tumors

• IRAS ID

  82840

• Contact name

  Ruth Plummer

• Eudract number

  2011-001959-37

• ISRCTN Number

  N/A

• Clinicaltrials.gov Identifier

  N/A

• Research summary

  E7449 is a potent inhibitor of both Poly (ADP-ribose) polymerase 1 (PARP1) and (PARP2) activity. PARP enzymes play a part in regulating and repairing damaged DNA. In normal cells this is useful and stops cell death however it is proposed that cancer cells use this action to their advantage. E7449 is a new compound which causes inhibition of PARP function and may disrupt the chemotherapy resistance in certain types of cancer cells. The study is funded by the pharmaceutical company Eisai Ltd who have developed E7449.This is a multicenter, open-label, Phase 1/2 study which will be conducted in three arms. Each arm will be conducted in two parts: a Phase 1 part which will include dose escalation and a Phase 2 part which will include four cohorts in specific disease indications. Arm 1: E7449 will be administered as a single agent.Arm 2: E7449 will be administered in combination with temozolomideArm 3: E7449 will be administered in combination with carboplatin and paclitaxelThe first part of the study is a Phase 1, Arm 1 (dose escalation of E7449) to find the maximum tolerated dose in patients with advanced stage solid tumors and B-cell malignancies. Once the recommended dose is achieved a further cohort of 9-12 patients will assess the safety and if there is any effect on E7449 when taken with food. The maximum tolerated dose (MTD) of E7449 in combination with temozolomide (Arm 2) and with Carboplatin and Paclitaxel (Arm 3) is then determined in patients with advanced solid tumors. A Phase 2 part will then determine response rates and/or stable disease to E7449, single agent and in combination with temozolomdie and with carboplatin and paclitaxel in patients with B-cell malignancies, advanced ovarian cancer, metastatic breast cancer and advanced melanoma, (Arms 1, 2 and 3).

• REC name

  South Central - Berkshire B Research Ethics Committee

• REC reference

  11/SC/0377

• Date of REC Opinion

  17 Oct 2011

• REC opinion

  Further Information Favourable Opinion