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Efficacy and safety of nab-paclitaxel in patients with previously treated metastatic colorectal cancer: a phase II COLO-001 trial

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Abstract

Purpose

This single-arm, phase II trial evaluated nab-paclitaxel monotherapy in pretreated patients with metastatic colorectal cancer (mCRC).

Methods

Patients with mCRC (RAS wild-type and RAS mutant cohorts) received nab-paclitaxel 125 mg/m2 days 1, 8, and 15 (28-day cycle). The primary endpoint was investigator-assessed progression-free survival (PFS) rate at week 8; secondary endpoints included overall survival, overall response rate, and safety. Stage 1 planned enrollment was 15 patients per cohort per Simon 2-stage design. Stage 2 enrollment was to continue unless ≤8 of the first 15 patients per cohort achieved PFS at 8 weeks.

Results

Stage 1 enrolled 41 patients (RAS wild type: n = 18; RAS mutant: n = 23). In both RAS cohorts, 3 of 15 patients initially enrolled were progression-free at week 8 (20%; 95% CI 4.0–48.0). Median PFS was 8.1 weeks (95% CI 7.7–8.6) and 7.9 weeks (95% CI 7.6–8.0) for RAS wild-type and RAS mutant cohorts, respectively. There were no complete or partial responses. The overall disease control rate was 16% (95% CI 6.0–32.0), and rates were similar in the RAS wild-type and RAS mutant cohorts (18 and 15%, respectively). No new safety signals were reported; the most common grade ≥3 adverse events included neutropenia, asthenia, and peripheral neuropathy. This study did not progress to stage 2 per the preplanned statistical stopping rule.

Conclusions

In patients with heavily pretreated mCRC, nab-paclitaxel did not demonstrate promising antitumor activity; further assessment of nab-paclitaxel monotherapy in this population of patients is not supported.

Trial registration

NCT02103062.

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Acknowledgements

The authors thank Valérie Boige, David Malka, Pascal Burtin, and Antoine Hollebecque at the Gustave Roussy Cancer Campus, Farid El Hajbi at the Centre Oscar Lambret, and Desmond McGovern at Celgene for their support. Medical writing assistance was provided by Dena Jacob, PhD, MediTech Media, Ltd, funded by Celgene Corporation. The authors were fully responsible for all content and editorial decisions for this manuscript.

Funding

The study was funded by Celgene Corporation.

Author information

Authors and Affiliations

  1. Gustave Roussy, Cancer Campus Grand Paris, Villejuif, France

    Michel Ducreux

  2. Institut de Cancérologie de l’Ouest, Site Hospitalier Nord, Saint-Herblain, France

    Jaafar Bennouna

  3. Centre Oscar Lambret, Lille, France

    Antoine Adenis

  4. Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France

    Thierry Conroy

  5. Institut Curie, Hôpital René Huguenin, Saint Cloud, France

    Astrid Lièvre

  6. CHU Pontchaillou, Rennes, France

    Astrid Lièvre

  7. Institut du Cancer de Montpellier, Montpellier, France

    Fabienne Portales

  8. Celgene Corporation, 86 Morris Avenue, Summit, NJ, USA

    Julie Jeanes & Li Li

  9. Celgene International Sàrl, Boudry, Switzerland

    Alfredo Romano

  10. Université Paris-Saclay, Saclay, France

    Michel Ducreux

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  1. Michel Ducreux
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Corresponding author

Correspondence to Michel Ducreux.

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Conflict of interest

MD, receipt of grants/research supports: Roche, Chugai, Pfizer; receipt of honoraria or consultation fees: Roche, Celgene, Merck Serono, Amgen, Novartis, Sanofi, Pfizer; JB, receipt of honoraria or consultation fees: Roche, Boehringer Ingelheim, AstraZeneca; AA, nothing to disclose; TC, nothing to disclose; AL, receipt of grants/research supports: Merck Serono; receipt of honoraria or consultation fees: Merck Serono, Roche, Amgen, Sanofi, Lily; FP, nothing to disclose; JJ, LL, AR, employment or leadership and stock ownership: Celgene.

Ethics approval

All relevant ethical approvals from institutional review board/independent ethics committee have been obtained prior to study commencement.

Informed consent

Informed consent was obtained from all patients prior to study entry.

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Ducreux, M., Bennouna, J., Adenis, A. et al. Efficacy and safety of nab-paclitaxel in patients with previously treated metastatic colorectal cancer: a phase II COLO-001 trial. Cancer Chemother Pharmacol 79, 9–16 (2017). https://doi.org/10.1007/s00280-016-3193-5

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  • DOI: https://doi.org/10.1007/s00280-016-3193-5

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