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Phase I/II trial of carboplatin, nab-paclitaxel and bevacizumab for advanced non-squamous non-small cell lung cancer (CARNAVAL; TORG1424/OLCSG1402): results of the phase I part

Date

18 Dec 2016

Session

Poster lunch

Presenters

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

Author affiliations

  • 1 Respiratory Medicine, Japanese Red Cross Okayama Hospital, 700-8607 - Okayama/JP
  • 2 Thoracic Oncology And Medicine, Shikoku Cancer Center, 791-0280 - Matsuyama/JP
  • 3 Respiratory Medicine, Okayama University Hospital, 700-8558 - Okayama/JP
  • 4 Respiratory Medicine, Kurashiki Central Hospital, 710-8602 - Kurashiki/JP
  • 5 Oncology Clinical Development, Gunma University Graduate School of Medicine, 371-8511 - Maebashi/JP
  • 6 Thoracic Oncology, Kanagawa Cancer Center, 241-8515 - Yokohama/JP
  • 7 Thoracic Oncology, Thoracic Oncology Research Group, 222-0033 - Yokohama/JP
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Background

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.

Methods

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.

Results

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.

Conclusions

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

Funding

Taiho Pharmaceutical Co., Ltd.

Disclosure

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.

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