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APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers

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: NCT03165994
Recruitment Status : Active, not recruiting
First Posted : May 24, 2017
Last Update Posted : April 29, 2022
Sponsor:
Information provided by (Responsible Party):
Apexigen, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Esophageal Cancer GastroEsophageal Cancer Drug: APX005M Radiation: Radiation Therapy Drug: Paclitaxel Drug: Carboplatin Procedure: Surgical resection of tumor Phase 2

Detailed Description:

Primary Objective:

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

Secondary Objectives:

  1. To further characterize the safety and feasibility of combining APX005M with SOC chemoradiation (external beam radiation in daily fractions, with concurrent weekly low-dose carboplatin/paclitaxel) in the neoadjuvant setting for patients with resectable esophageal and GE junction cancers.
  2. To assess the efficacy of combining APX005M with SOC chemoradiation as measured by rates of R0 resection (microscopically negative margins, i.e., no tumor remains following surgery); and radiographic/metabolic response to neoadjuvant treatment on CT-PET.

Exploratory Objectives:

  1. To identify possible predictive molecular or immune-based efficacy biomarkers for this novel combination.
  2. To characterize and assess overall survival.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Non-comparative, open-label pilot study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of APX005M in Combination With Concurrent Chemoradiation as Neoadjuvant Therapy for Resectable Esophageal and Gastroesophageal Junction Cancers
Actual Study Start Date : October 6, 2017
Estimated Primary Completion Date : April 30, 2022
Estimated Study Completion Date : April 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: APX005M with chemoradiation

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

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 area under curve (AUC) 2. Paclitaxel dose will be 50mg/m2.

Surgical resection of tumor: between weeks 10-16

Drug: APX005M
APX005M intravenous (IV) infusion
Other Name: CD40 Agonistic Monoclonal Antibody)

Radiation: Radiation Therapy
Radiation therapy, total dose 5040cGy in 180cGy fractions
Other Name: Radiotherapy

Drug: Paclitaxel
Paclitaxel IV infusion
Other Name: Taxol

Drug: Carboplatin
Carboplatin IV infusion
Other Name: Paraplatin

Procedure: Surgical resection of tumor
Surgical removal of the tumor will occur between weeks 10-16
Other Names:
  • Surgery
  • Operation




Primary Outcome Measures :
  1. Pathologic complete response (pCR) rate [ Time Frame: At time of surgery (at 10-16 weeks) ]

Secondary Outcome Measures :
  1. Rates of R0 resection (microscopically negative margins, i.e., no tumor remains following surgery) [ Time Frame: At time of surgery ]
  2. Pathologic stage at time of surgery [ Time Frame: At time of surgery ]
  3. Radiographic/metabolic response to neoadjuvant treatment on Computed Tomography (CT) / CT-Positron Emission Tomography (PET) (CT-PET) [ Time Frame: Baseline, then at time of surgery, and 3 and 6 months post-operatively ]
  4. Frequency of adverse events [ Time Frame: Up to 5 months for each patient ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 Nx preferably by endoscopic ultrasound [EUS]). (Excluded: T1N0 tumors, cervical esophageal location, tumors invading the tracheobronchial tree or with fistula, distant disease that cannot be included in the radiation field or be resected at the time of esophagectomy)
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  5. Adequate hematological, renal, and hepatic parameters

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. History of autoimmune disorders with the exception of vitiligo or autoimmune thyroid disorders
  8. Chronic steroid dependency (prednisone equivalent > 10 mg/day). Any steroid use should be discontinued at least 2 weeks prior to initiation of study treatment.
  9. 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
  10. Known human immunodeficiency virus (HIV) infection

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): NCT03165994


Locations
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United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85719
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
University of California, San Francisco
San Francisco, California, United States, 94143
United States, District of Columbia
MedStar Georgetown University Hospital (MGUH)
Washington, District of Columbia, United States, 20007-2113
United States, New York
New York University
New York, New York, United States, 10016
United States, North Carolina
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7305
Wake Forest School of Medicine
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
University of Cincinnati Medical Center
Cincinnati, Ohio, United States, 45219
United States, Texas
Renovatio Clinical
The Woodlands, Texas, United States, 77380
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Apexigen, Inc.
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Responsible Party: Apexigen, Inc.
ClinicalTrials.gov Identifier: NCT03165994    
Other Study ID Numbers: APX005M-006
First Posted: May 24, 2017    Key Record Dates
Last Update Posted: April 29, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Apexigen, Inc.:
esophagus
gastroesophageal (GE) junction
T1-3N0-1
Additional relevant MeSH terms:
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Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action