Summary

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

Description

Summary

This pilot phase II trial studies the side effects of CD40 agonistic monoclonal antibody APX005M (APX005M), chemotherapy, and radiation therapy, and to see how well they work when given before surgery in treating patients with esophageal cancer or gastroesophageal cancer that can be removed by surgery. APX005M is intended to stimulate the body's own immune system so that the immune cells can more effectively invade and destroy the tumor, adding to the benefits of the chemotherapy and radiation therapy. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving APX005M, chemotherapy, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Official Title

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

Details

PRIMARY OBJECTIVES:

  1. To establish the safety and feasibility of combining APX005M with standard-of-care chemoradiation (external beam radiation in daily fractions, with concurrent weekly low-dose carboplatin/paclitaxel) in the neoadjuvant setting for patients with resectable esophageal and gastroesophageal junction (GEJ) cancers.

SECONDARY OBJECTIVES:

  1. To assess the efficacy of this novel combination, as measured by the pathologic complete response (pCR) rate.

OUTLINE:

Patients receive APX005M intravenously (IV) over 60 minutes during weeks 1, 4, 7, and 10, radiation therapy once daily (QD) for 5 days per week during weeks 3-8, and paclitaxel IV over 60 minutes and carboplatin IV over 60 minutes once weekly (days 1, 8, 15, 22, and 29) during weeks 3-8 in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery 1-7 weeks after last dose of APX005M.

After completion of study treatment, patients are followed up at 1, 3, and 6 months.

Keywords

Esophageal Cancer GastroEsophageal Cancer esophagus gastroesoophageal (GE) junction T1-3N0-1 Esophageal Neoplasms Paclitaxel Albumin-Bound Paclitaxel Carboplatin APX005M Radiation Therapy Surgical resection of tumor

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 Nx 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 accepting new patients
    San Francisco California 94143 United States

Lead Scientist

  • Andrew Ko
    Professor, Medicine. Authored (or co-authored) 84 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT03165994
Phase
Phase 2
Study Type
Interventional
Last Updated