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

NCT02273713 | Completed Phase 1

• 1 other identifier: NL 49837.018.14
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Cancer; Toxicity

Keywords

Esophageal cancer; Metastasized; Nab-paclitaxel; Toxicity; First line treatment; Phase Ib/II

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity

  Identifying the Maximum Tolerated Dose

  12 months

• Progression Free survival

  approximately 36 months

Secondary Outcomes (5)

• Adverse events

  approximately 36 months

• Response rate

  approximately 36 months

• Progression free survival

  approximately 36 months

• Neurotoxicity

  approximately 36 months

• Overall survival

  approximately 36 months

Study Arms (1)

Nab-Paclitaxel

EXPERIMENTAL

Nab-Paclitaxel added to first line treatment with Oxaliplatin and Capecitabine

Drug: Nab-paclitaxel

Interventions

Nab-paclitaxel DRUG

Nab-paclitaxel added to first line treatment oxaliplatin and capecitabine

Also known as: Abraxane

Nab-Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Celgene Corporation: collaborator

Study Sites (1)

Academic Medical Center, Medical Oncology

Amsterdam, 1100 DD, Netherlands

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Neoplasm Metastasis

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Hanneke WM van Laarhoven, Prof.Dr.

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: October 24, 2014
• Study Start: October 1, 2014
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: May 31, 2017

Record last verified: 2017-05

Locations

NL (1)