Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Addition of Nab-paclitaxel (Abraxane) to First Line Treatment of Metastasized Oesophagogastric Carcinoma (ACTION) (ACTION)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02273713
Recruitment Status : Completed
First Posted : October 24, 2014
Last Update Posted : May 31, 2017
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:

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

Detailed Description:

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 -

  1. (starting) 60 mg/m2 1000 mg/m2 65 mg/m2 3
  2. 80 mg/ m2 1000 mg/m2 65 mg/m2 3
  3. 100 mg/ m2 1000 mg/m2 65 mg/m2 3
  4. 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 154 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nab-Paclitaxel
Nab-Paclitaxel added to first line treatment with Oxaliplatin and Capecitabine
Drug: Nab-paclitaxel
Nab-paclitaxel added to first line treatment oxaliplatin and capecitabine
Other Name: Abraxane




Primary Outcome Measures :
  1. Dose Limiting Toxicity [ Time Frame: 12 months ]
    Identifying the Maximum Tolerated Dose

  2. Progression Free survival [ Time Frame: approximately 36 months ]

Secondary Outcome Measures :
  1. Adverse events [ Time Frame: approximately 36 months ]
    Adverse event, serious adverse events according to NCI CTC version 4.0

  2. Response rate [ Time Frame: approximately 36 months ]
    Response rate according to RECIST 1.1

  3. Progression free survival [ Time Frame: approximately 36 months ]
  4. Neurotoxicity [ Time Frame: approximately 36 months ]
    Self reported neurotoxicity according to EORTC QLQ CIPN20

  5. Overall survival [ Time Frame: approximately 36 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must provide written informed consent according to ICH/GCP, and national/local regulations prior to any screening procedures.
  • Patients with histologically confirmed diagnosis of metastatic or irresectable carcinoma of the stomach or oesophagus
  • Patients with metastatic or irresectable carcinoma of the stomach or oesophagus not pre-treated with chemotherapy or radiotherapy for irresectable or metastatic disease.
  • Measurable disease as assessed by RECIST 1.1
  • ECOG (WHO) performance status 0-2
  • Patient has adequate bone marrow and organ function
  • If a female patient is of child-bearing potential: negative serum pregnancy test, If sexually active, the patient must agree to use contraception.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Exclusion Criteria:

  • Prior systemic treatment for metastatic or irresectable stomach or oesophageal cancer.
  • Evidence of disease progression within 3 months after completion of adjuvant or neoadjuvant treatment containing capecitabine and/or oxaliplatin.
  • History of hypersensitivity to nab-paclitaxel, capecitabine or oxaliplatin.
  • All target lesions in a radiation field without documented disease progression.
  • WHO 2-4
  • Use of other investigational drugs within 30 days of enrollment.
  • Patient has known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no oedema, no steroids and stable in 2 scans at least 4 weeks apart).
  • History of malignancy in the last 5 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years.
  • Patients who are not willing to avoid consumption of Seville oranges, grapefruit or grapefruit juice grapefruit hybrids, pomelos and exotic citrus fruits during the entire study.
  • Patient is currently being treated with drugs known to be strong inhibitors or inducers of CYP3A4 or CYP2C8, which cannot be discontinued or switched to a different medication 7 days prior to starting study treatment and for the duration of the study.
  • Patient has active, uncontrolled bacterial, viral or fungal infection(s) requiring systemic therapy.
  • Patient has known historical or active infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
  • Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate patient participation in the clinical study (e.g. hematological, cardiovascular, lung disease etc)
  • Patient is enrolled in any other clinical protocol or investigational trial with the same primary endpoint.
  • Patients who in the investigators' opinion may be unwilling, unable or unlikely to comply with requirements of the study protocol.

Information from the National Library of Medicine

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


Locations
Layout table for location information
Netherlands
Academic Medical Center, Medical Oncology
Amsterdam, Netherlands, 1100 DD
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Celgene Corporation
Investigators
Layout table for investigator information
Principal Investigator: Hanneke WM van Laarhoven, Prof.Dr. Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Layout table for additonal information
Responsible Party: H.W.M. van Laarhoven, Prof. dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02273713    
Other Study ID Numbers: NL 49837.018.14
First Posted: October 24, 2014    Key Record Dates
Last Update Posted: May 31, 2017
Last Verified: May 2017
Keywords provided by H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Esophageal cancer
Metastasized
Nab-paclitaxel
Toxicity
First line treatment
Phase Ib/II
Additional relevant MeSH terms:
Layout table for MeSH terms
Esophageal Neoplasms
Neoplasm Metastasis
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Neoplastic Processes
Pathologic Processes
Paclitaxel
Albumin-Bound Paclitaxel
Capecitabine
Oxaliplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites