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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California
study started
estimated completion:

Description

Summary

This study evaluates APX005M, in combination with chemoradiation, in patients with resectable cancers of the esophagus and gastroesophageal (GE) junction, including both squamous cell and adenocarcinomas.

Official Title

A Pilot Study of APX005M in Combination With Concurrent Chemoradiation as Neoadjuvant Therapy for Resectable Esophageal and Gastroesophageal Junction Cancers

Details

This is a non-comparative open-label multicenter pilot study of APX005M in patients with resectable (T1-3N0-1, excluding T1N0) cancers of the esophagus and GE junction, including both squamous cell and adenocarcinomas.

Safety and toxicity will be assessed on a continuous basis throughout the course of study treatment by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03.

Regular clinical assessments will be performed throughout the course of study treatment, including physical exams, CT-PET scan at the completion of chemoradiation, and assessment of pathologic response at the time of surgery.

Immunotherapeutic approaches have demonstrated clear evidence of therapeutic activity in a subset of patients with advanced gastroesophageal cancers. CD40 agonistic antibodies represent an attractive and novel form of immunotherapy that stimulate an immune response by activating antigen processing and presentation, recruiting immune effectors such as natural killer (NK) cells and macrophages, and additionally have direct cytotoxic effects on tumor cells. However, the activity of this class of agents in esophageal/GE junction cancers is unknown and will be evaluated in the context of this study by combining it with standard chemoradiation in the neoadjuvant setting, with serial collection of tissue and blood along the way for correlative purposes to monitor on-target treatment and pharmacodynamics effects. This study represents the first of its kind to evaluate the safety and preliminary efficacy of combining a CD40 agonist antibody with standard chemoradiation in patients with resectable disease.

Keywords

Esophageal Cancer GastroEsophageal Cancer esophagus gastroesoophageal (GE) junction T1-3N0-1 Esophageal Neoplasms Paclitaxel Albumin-Bound Paclitaxel Carboplatin

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Age ≥ 18 years of age
  2. Histologically proven squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the esophagus or GE junction.
  3. Surgically resectable (T1-3 N0-1 by endoscopic ultrasound). Excluded are:
  4. Very early stage tumors (T1N0)
  5. Cervical esophageal tumors
  6. Tumors invading the tracheobronchial tree or associated with tracheoesophageal fistula
  7. Any evidence of distant metastases (as determined by endoscopic ultrasound (EUS)or CT/PET)
  8. Cervical, supraclavicular, or other nodal disease that is either not included in the radiation field or is not able to be resected at the time of esophagectomy
  9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  10. Adequate hematological, renal, and hepatic parameters defined as follows:
  11. Absolute Neutrophil Count (ANC) ≥1.5 × 109/L in absence of growth factor support
  12. Platelet count ≥150 × 109/L
  13. Hemoglobin >9 g/dL
  14. Serum creatinine ≤1.5 mg/dL, or calculated (using the formula of Cockcroft and Gault) or measured creatinine clearance ≥30 mL/min
  15. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN)
  16. Total bilirubin ≤1.5x ULN
  17. Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within the 7 days prior to investigational product administration and a negative urine pregnancy test within the 3 days prior to the first investigational product administration, or a negative serum pregnancy test within the 3 days prior to the first investigational product administration
  18. WOCBP and male subjects who are sexually active with WOCBP must agree to use 2 highly effective methods of contraception (including a physical barrier) during the study and for 30 days following the last dose of investigational product
  19. Ability to understand a written informed consent document, and the willingness to sign it

You CAN'T join if...

  1. Any history of or current hematologic malignancy
  2. History of a second primary cancer is allowed in the event the cancer is curatively resected and there is no evidence of recurrence/metastatic disease x 1 year. Subjects who have a history of cervical or breast carcinoma in situ, localized prostate cancer,adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder tumors [Ta, Tis & T1] are also allowed
  3. Major surgery within 4 weeks of first dose of investigational product
  4. Prior or concurrent treatment with any anticancer agent for the same cancer diagnosis
  5. Prior exposure to any immuno-oncology agents, including CD40/PD-1/PD-L1/CTLA-4 inhibitors (if any ambiguity, should be discussed with study principal investigator)
  6. History of bone marrow transplantation
  7. Uncontrolled diabetes or hypertension
  8. History of autoimmune disorders with the exception of vitiligo or autoimmune thyroid disorders
  9. Chronic steroid dependency (prednisone equivalent > 10 mg/day). Any steroid use should be discontinued at least 2 weeks prior to initiation of study treatment.
  10. . History of sensitivity or allergy to monoclonal antibodies (mAbs) or immunoglobulin G(IgG)
  11. . History of severe hypersensitivity reaction to Cremaphor EL.
  12. . Pre-existing > grade 2 peripheral sensory neuropathy.
  13. . Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months before first dose
  14. . History of any arterial thromboembolic event within 3 months prior to first dose of investigational product
  15. . Active coagulopathy
  16. . Active known clinically serious infections (> Grade 2 National Cancer Institute (NCI)- CTCAE version 4.03)
  17. . Known human immunodeficiency virus (HIV) infection
  18. . Subjects of reproductive potential who do not use effective methods of birth control
  19. . Pregnant or actively breastfeeding women
  20. . Any clinically significant psychiatric, social, or medical condition that, in the opinion of the Investigator, could increase subject's risk, interfere with protocol adherence, or affect a subject's ability to give informed consent.

Location

  • University of California, San Francisco not yet accepting patients
    San Francisco, California, 94143, United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT03165994
Phase
Phase 2
Lead Scientist
Andrew H Ko
Study Type
Interventional
Last Updated
August 28, 2017
I’m interested in this study!