460P - Phase I/II trial of carboplatin, nab-paclitaxel and bevacizumab for advanced non-squamous non-small cell lung cancer (CARNAVAL; TORG1424/OLCSG1402)...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anticancer Agents
Non-Small-Cell Lung Cancer, Metastatic
Presenter Akihiro Bessho
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors A. Bessho1, N. Nogami2, T. Kubo3, H. Kitajima2, S. Ikeo4, K. Kaira5, S. Hosokawa1, H. Yoshioka4, S. Murakami6, K. Watanabe7, K. Kiura3
  • 1Respiratory Medicine, Japanese Red Cross Okayama Hospital, 700-8607 - Okayama/JP
  • 2Thoracic Oncology And Medicine, Shikoku Cancer Center, 791-0280 - Matsuyama/JP
  • 3Respiratory Medicine, Okayama University Hospital, 700-8558 - Okayama/JP
  • 4Respiratory Medicine, Kurashiki Central Hospital, 710-8602 - Kurashiki/JP
  • 5Oncology Clinical Development, Gunma University Graduate School of Medicine, 371-8511 - Maebashi/JP
  • 6Thoracic Oncology, Kanagawa Cancer Center, 241-8515 - Yokohama/JP
  • 7Thoracic Oncology, Thoracic Oncology Research Group, 222-0033 - Yokohama/JP



Nanoparticle albumin-bound paclitaxel (nab-PTX) is a new formulation of paclitaxel and has demonstrated efficacy when combined with carboplatin (Cb), resulting in one of the standard platinum-containing chemotherapy regimens for patients (pts) with chemo-naïve advanced non-small cell lung cancer (NSCLC). The addition of bevacizumab (BEV) to chemotherapy has been known an effective treatment option for non-squamous NSCLC. The efficacy and safety of the new triplet regimen: Cb + nab-PTX + BEV has not yet been assessed.


We planned multicenter, open-label, phase I/II trial of Cb + nab-PTX + BEV (CARNAVAL; TORG1424/OLCSG1402). Eligible pts were chemo-naïve, aged ≥20 years, ECOG PS 0/1 with advanced non-squamous NSCLC. Pts received 4 to 6 cycles of Cb (AUC = 6, day1) + nab-PTX (dose level 1; 100mg/m2 on days 1, 8 or dose level 2; 100mg/m2 on days 1, 8, and 15) + BEV (15mg/kg, day1) followed by maintenance nab-PTX + BEV every 3 weeks until disease progression. The phase I part of the study used a 6 + 6 dose-escalation design to determine the maximum tolerated dose. Major dose-limiting toxicity (DLT) was defined as grade 4 neutropenia for at least 4 consecutive days, febrile neutropenia, grade 4 thrombocytopenia, grade ≥3 non-hematologic toxicity (excluding nausea, vomiting, loss of appetite, fatigue, diarrhea, constipation, disorder of electrolyte, hypertension and hypersensitivity, if they are manageable), and grade 4 hypertension. DLT was assessed during 1st cycle.


From October 2014 to July 2015, 4 and 12 pts were enrolled at dose level 1 and 2 cohorts respectively. No DLT was observed at either level and recommended phase II dose (RP2D) was determined at dose level 2. Grade ≥3 adverse events (AEs) during the overall treatment period were as follows; neutropenia (13 pts), thrombocytopenia (4 pts), nausea, vomiting, anorexia (3 pts each), anemia, fatigue, hypertension (2 pts each), pneumonitis, liver disorder, hyponatremia, febrile neutropenia, skin ulcer, esophageal perforation (1 pt each). All AEs were manageable.


RP2D of Cb + nab-PTX + BEV was determined at dose level 2. We have started the phase II part of the trial at dose level 2 since November 2015.

Clinical trial indentification

UMIN Clinical Trials Registry, ID: 000014560

Legal entity responsible for the study

Thoracic Oncology Research Group: TORG


Taiho Pharmaceutical Co., Ltd.


A. Bessho: Honoraria: Chugai Pharmaceutical Co. N. Nogami, K. Kiura: Honoraria: Chugai Pharmaceutical Co., Taiho Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.