Division of Medical Oncology and Hematology, Rm 5-708, Princess Margaret Hospital, 610 University Avenue, Toronto M5G2M9, Canada.
Invest New Drugs. 2012 Apr;30(2):779-86. doi: 10.1007/s10637-010-9611-3. Epub 2010 Dec 18.
This phase I/II study of saracatinib in combination with gemcitabine in patients with advanced pancreatic cancer was conducted by the NCIC Clinical Trials Group. The aims were to define the recommended phase II dose (RP2D) of saracatinib when combined with gemcitabine, and assess the efficacy of this combination in advanced pancreatic cancer.
Eligibility criteria included locally advanced or metastatic pancreatic adenocarcinoma and no prior chemotherapy. In phase I saracatinib was escalated in combination with gemcitabine (1000 mg/m(2)) to determine the recommended phase II dose (RP2D). The study was then expanded to a single arm phase II trial using a Simon 2-stage design. The primary endpoint was objective tumor response (OR) plus stable disease ≥ 4 months (SD4) rate; if ≥ 8 patients had OR+SD4, the study would proceed to stage 2.
Thirteen patients were enrolled into the phase I portion of this study. Saracatinib 175 mg PO daily was chosen as the RP2D in combination with gemcitabine. Twenty-one additional patients were then enrolled at the RP2D (phase II). Of the 22 response evaluable patients treated at the RP2D, 9 patients (40.9%) had progressive disease, 6 patients (27.3%) had stable disease for less than 4 months, 5 patients (22.7%) had SD4, and 2 patients (9.1%) had a partial response to treatment. Objective criteria for continuing to stage 2 were thus not met and the trial was closed following the accrual of 34 patients.
Saracatinib 175 mg daily in combination with gemcitabine is well tolerated but the combination did not improve efficacy over what would be expected from gemcitabine alone.
这项由加拿大国立癌症研究所临床试验组进行的 I/II 期研究评估了沙卡替尼联合吉西他滨治疗晚期胰腺癌患者的疗效和安全性。目的是确定沙卡替尼联合吉西他滨的推荐 II 期剂量（RP2D），并评估该联合方案在晚期胰腺癌中的疗效。
入选标准包括局部晚期或转移性胰腺腺癌，且无既往化疗史。在 I 期研究中，沙卡替尼联合吉西他滨（1000mg/m²）进行剂量递增，以确定推荐的 II 期剂量（RP2D）。然后，采用 Simon 两阶段设计进行单臂 II 期试验扩展。主要终点为客观肿瘤缓解（OR）+稳定疾病≥4 个月（SD4）率；如果≥8 例患者达到 OR+SD4，则研究进入 II 期。
本研究 I 期部分共纳入 13 例患者。沙卡替尼 175mg PO 每日 1 次联合吉西他滨被选为 RP2D。随后，在 RP2D 水平上进一步入组 21 例患者（II 期）。在接受 RP2D 治疗的 22 例可评估疗效的患者中，9 例（40.9%）患者疾病进展，6 例（27.3%）患者 SD4 持续时间<4 个月，5 例（22.7%）患者 SD4，2 例（9.1%）患者部分缓解。因此，客观标准不符合继续进行 II 期研究的条件，在入组 34 例患者后，该试验关闭。
沙卡替尼 175mg 每日 1 次联合吉西他滨治疗耐受性良好，但联合治疗并未提高疗效，与单独使用吉西他滨相比，无明显改善。
