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History of Changes for Study: NCT03165994
APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers
Latest version (submitted April 28, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 May 23, 2017 None (earliest Version on record)
2 August 8, 2017 Study Status
3 August 28, 2017 Study Status
4 October 16, 2017 Recruitment Status, Study Status and Contacts/Locations
5 April 6, 2018 Contacts/Locations, Study Description, Study Status, Eligibility, Outcome Measures and Study Identification
6 April 8, 2019 Study Status, Arms and Interventions and Study Description
7 November 20, 2019 Sponsor/Collaborators, Study Status, Eligibility, Arms and Interventions, Study Design, Conditions and Study Identification
8 April 25, 2020 Sponsor/Collaborators, Contacts/Locations, Study Identification, Study Status and Oversight
9 August 3, 2020 Contacts/Locations and Study Status
10 August 7, 2020 Contacts/Locations and Study Status
11 August 14, 2020 Study Status and Contacts/Locations
12 September 30, 2020 Contacts/Locations and Study Status
13 January 8, 2021 Contacts/Locations and Study Status
14 June 28, 2021 Contacts/Locations and Study Status
15 October 14, 2021 Outcome Measures, Study Status, Arms and Interventions, Eligibility, Study Design and Study Description
16 April 28, 2022 Recruitment Status, Study Status, Contacts/Locations and Study Design
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Study NCT03165994
Submitted Date:  May 23, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: CC# 17701
Brief Title: APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers
Official Title: A Pilot Study of APX005M in Combination With Concurrent Chemoradiation as Neoadjuvant Therapy for Resectable Esophageal and Gastroesophageal Junction Cancers
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2017
Overall Status: Not yet recruiting
Study Start: July 1, 2017
Primary Completion: July 1, 2019 [Anticipated]
Study Completion: December 1, 2019 [Anticipated]
First Submitted: May 23, 2017
First Submitted that
Met QC Criteria:
May 23, 2017
First Posted: May 24, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
May 23, 2017
Last Update Posted: May 24, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: University of California, San Francisco
Responsible Party: Sponsor
Collaborators: Apexigen, Inc.
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief 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.
Detailed Description:

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.

Open or close this module Conditions
Conditions: Esophageal Cancer
GastroEsophageal Cancer
Keywords: esophagus
gastroesoophageal (GE) junction
T1-3N0-1
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Non-comparative, open-label pilot study
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 16 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: APX005M with chemoradiation

APX005M: 0.3mg/kg dose intravenously over 1 hour, every 3 weeks x 4 doses (weeks 1, 4, 7, and 10). Treatment begins 2 weeks prior to concurrent chemoradiation (chemoRT); continues during weeks 2 and 5 of chemoRT; and finishes with one final dose post-chemoRT and prior to surgery.

Daily radiation therapy (RT): 28 fractions (28 days)

Chemotherapy: Carboplatin and paclitaxel will be given intravenously over 1 hour, once weekly, for 5 weeks (days 1, 8, 15 22, and 29 of RT). Carboplatin dose will be AUC 2. Paclitaxel dose will be 50mg/m2.

Surgical resection of tumor: between weeks 11-17

Drug: APX005M
APX005M intravenous (IV) infusion
Other Names:
  • CD40 Agonistic Monoclonal Antibody)
Radiation: Radiation Therapy
Radiation therapy, total dose 5040cGy in 180cGy fractions
Other Names:
  • Radiotherapy
Drug: Paclitaxel
Paclitaxel IV infusion
Other Names:
  • Taxol
Drug: Carboplatin
Carboplatin IV infusion
Other Names:
  • Paraplatin
Procedure: Surgical resection of tumor
Surgical removal of the tumor will occur between weeks 11-17
Other Names:
  • Surgery
  • Operation
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Frequency of adverse events based on the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03
[ Time Frame: Over the period from baseline up to 6 months following the operation (up to 11 months in total) ]

Adverse events will be summarized by presenting, at each dose level, the number and percentage of patients having any adverse event, having an adverse event in each body system and having each individual adverse event. If no patients require a delay in their planned surgery for reasons of toxicity, the study will be considered feasible.
Secondary Outcome Measures:
1. Pathologic complete response (pCR) rate
[ Time Frame: At time of surgery (at 11-17 weeks) ]

The proportion of patients who achieve a pathologic complete remission. The point estimate and its 95% confidence interval will be obtained.
2. Radiographic/metabolic response to neoadjuvant treatment on Computed Tomography (CT) - Positron Emission Tomography (PET) (CT-PET)
[ Time Frame: Baseline, then at time of surgery, and 1, 3 and 6 months post-operatively ]

The radiographic/metabolic response will be described in qualitative terms (i.e., improved/stable/worse).

Response will be adjudicated by the treating provider, based on combination of change in wall thickening, size of regional lymph nodes, and metabolic activity of involved areas, and will be categorized as either responding, stable/unchanged, progressing, or not evaluable.

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  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:
    1. Very early stage tumors (T1N0)
    2. Cervical esophageal tumors
    3. Tumors invading the tracheobronchial tree or associated with tracheoesophageal fistula
    4. Any evidence of distant metastases (as determined by endoscopic ultrasound (EUS) or CT/PET)
    5. 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
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  5. Adequate hematological, renal, and hepatic parameters defined as follows:
    1. Absolute Neutrophil Count (ANC) ≥1.5 × 109/L in absence of growth factor support
    2. Platelet count ≥150 × 109/L
    3. Hemoglobin >9 g/dL
    4. Serum creatinine ≤1.5 mg/dL, or calculated (using the formula of Cockcroft and Gault) or measured creatinine clearance ≥30 mL/min
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN)
    6. Total bilirubin ≤1.5x ULN
  6. 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
  7. 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
  8. Ability to understand a written informed consent document, and the willingness to sign it

Exclusion Criteria:

  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.
Open or close this module Contacts/Locations
Central Contact Person: Andrew H Ko, MD
Telephone: 415-353-7286
Email: andrew.ko@ucsf.edu
Central Contact Backup: Joy Cannon
Telephone: 415-502-3498
Email: joy.cannon@ucsf.edu
Study Officials: Andrew H Ko, MD
Principal Investigator
University of California, San Francisco
Locations: United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Contact:Contact: Andrew H Ko, MD 415-353-7286 andrew.ko@ucsf.edu
Contact:Contact: Joy Cannon 415-502-3498 joy.cannon@ucsf.edu
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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