The Addition of Nab-paclitaxel (Abraxane) to First Line Treatment of Metastasized Oesophagogastric Carcinoma (ACTION) (ACTION)
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|ClinicalTrials.gov Identifier: NCT02273713|
Recruitment Status : Completed
First Posted : October 24, 2014
Last Update Posted : May 31, 2017
Oesophagogastric cancer is a major cause of cancer related mortality, with an overall 5-year survival rate of 10% worldwide and patients are often diagnosed with locally advanced or metastasized disease at first presentation. For advanced oesophagogastric cancer fluoropyrimidines are the backbone of palliative chemotherapy and is commonly used in 2- or 3-drug combinations .
However, in clinical practice after progression on first line therapy, a substantial number of oesophagogastric cancer patients may not be able to start second line chemotherapy due to rapid clinical deterioration. Therefore, new triplets with high anti-tumor activity and low toxicity are urgently needed.
Given the activity of capecitabine and oxaliplatin containing regimens and the potential of taxanes in oesophagogastric cancer, the investigators propose a phase I study combining capecitabine and oxaliplatin with Nab-paclitaxel.
Solvent-based taxanes (paclitaxel, docetaxel) can cause severe toxicities not only by the active agents itself but also by the solvents like cremophor. Nab-paclitaxel (Abraxane) is a solvent-free formulation of paclitaxel encapsulated in albumin. It does not require premedication with corticosteroids or antihistamines to prevent the risk of solvent-mediated hypersensitivity reactions. This new formulation improves safety profile, allows higher dosing with shorter infusion duration, and produces higher tumor drug concentration. It has proven activity in breast cancer, non small lung cancer and pancreatic cancer, as well as in gastric cancer models.
|Condition or disease||Intervention/treatment||Phase|
|Esophageal Cancer Toxicity||Drug: Nab-paclitaxel||Phase 1 Phase 2|
Phase 1: To assess the safety and tolerability of Nab-paclitaxel added to oxaliplatin and capecitabine at their currently optimal doses.
Phase 2: To determine the anti-tumor activity of Nab-paclitaxel when co-administered with oxaliplatin and capecitabine in patients with irresectable or metastasized oesophagogastric cancer in terms of progression free survival.
Study design This is a single-center, open label, dose finding, phase I/II study.
Intervention In the phase I part of the study, the dose of nab-paclitaxel in combination of capecitabine and oxaliplatin will be escalated in fixed increments according to the dose escalation scheme outlined below
Dose level Nab-paclitaxel Capecitabine Oxaliplatin Minimum Day 1 and 8 14 days Day 1 and 8 number of patients -1 40 mg/m2 1000 mg/m2 65 mg/m2 -
- (starting) 60 mg/m2 1000 mg/m2 65 mg/m2 3
- 80 mg/ m2 1000 mg/m2 65 mg/m2 3
- 100 mg/ m2 1000 mg/m2 65 mg/m2 3
- 120 mg/ m2 1000 mg/m2 65 mg/m2 3
In the phase II part of the study the maximum tolerated dose from the phase I part of the study will be used in combination with fixed dosages of capecitabine and oxaliplatin; nab-paclitaxel day 1 and 8 according to the Maximum Tolerated Dose (MTD) of the phase 1 part of the study combined with capecitabine for 14 days at 1000mg/m2 twice daily and oxaliplatin day 1 and 8 65mg/m2.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||154 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The ACTION Trial: a Phase Ib/II Study on the Addition of Nab-paclitaxel (Abraxane) to Capecitabine and Oxaliplatin in the First-line Treatment of Metastasized Oesophagogastric Carcinoma.|
|Study Start Date :||October 2014|
|Actual Primary Completion Date :||March 2017|
|Actual Study Completion Date :||March 2017|
Nab-Paclitaxel added to first line treatment with Oxaliplatin and Capecitabine
Nab-paclitaxel added to first line treatment oxaliplatin and capecitabine
Other Name: Abraxane
- Dose Limiting Toxicity [ Time Frame: 12 months ]Identifying the Maximum Tolerated Dose
- Progression Free survival [ Time Frame: approximately 36 months ]
- Adverse events [ Time Frame: approximately 36 months ]Adverse event, serious adverse events according to NCI CTC version 4.0
- Response rate [ Time Frame: approximately 36 months ]Response rate according to RECIST 1.1
- Progression free survival [ Time Frame: approximately 36 months ]
- Neurotoxicity [ Time Frame: approximately 36 months ]Self reported neurotoxicity according to EORTC QLQ CIPN20
- Overall survival [ Time Frame: approximately 36 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02273713
|Academic Medical Center, Medical Oncology|
|Amsterdam, Netherlands, 1100 DD|
|Principal Investigator:||Hanneke WM van Laarhoven, Prof.Dr.||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|