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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.

Tracking Information
First Submitted Date  ICMJE May 23, 2017
First Posted Date  ICMJE May 24, 2017
Last Update Posted Date April 29, 2022
Actual Study Start Date  ICMJE October 6, 2017
Estimated Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2021)
Pathologic complete response (pCR) rate [ Time Frame: At time of surgery (at 10-16 weeks) ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 23, 2017)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2021)
  • Rates of R0 resection (microscopically negative margins, i.e., no tumor remains following surgery) [ Time Frame: At time of surgery ]
  • Pathologic stage at time of surgery [ Time Frame: At time of surgery ]
  • 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 ]
  • Frequency of adverse events [ Time Frame: Up to 5 months for each patient ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2017)
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers
Official Title  ICMJE A Phase 2 Study of APX005M in Combination With Concurrent Chemoradiation as Neoadjuvant Therapy for Resectable Esophageal and Gastroesophageal Junction Cancers
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Non-comparative, open-label pilot study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Esophageal Cancer
  • GastroEsophageal Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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

Interventions:
  • Drug: APX005M
  • Radiation: Radiation Therapy
  • Drug: Paclitaxel
  • Drug: Carboplatin
  • Procedure: Surgical resection of tumor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 28, 2022)
34
Original Estimated Enrollment  ICMJE
 (submitted: May 23, 2017)
16
Estimated Study Completion Date  ICMJE April 30, 2024
Estimated Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03165994
Other Study ID Numbers  ICMJE APX005M-006
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Apexigen, Inc.
Original Responsible Party University of California, San Francisco
Current Study Sponsor  ICMJE Apexigen, Inc.
Original Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Apexigen, Inc.
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP