Clinical trial NCT03165994: APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers
Official title: A Phase 2 Study of APX005M in Combination With Concurrent Chemoradiation as Neoadjuvant Therapy for Resectable Esophageal and Gastroesophageal Junction Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
GastroEsophageal Cancer
Keywords: esophagus
gastroesophageal junction
T1-3N0-1
GE junction
Lead sponsor: Apexigen America, Inc.
Sponsor class: INDUSTRY
First posted: 2017-05-24
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-comparative, open-label pilot study
Primary purpose: TREATMENT

Brief summary: This pilot phase II trial studies the therapeutic effects and side effects of CD40 agonistic monoclonal antibody APX005M when combined with chemotherapy and radiation therapy, and to see how well they work to reduce or remove esophageal or gastroesophageal (GE) cancers when given before surgery in treating patients with esophageal cancer or GE cancer than 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.

Eligibility 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.

Primary outcomes:
measure: Pathologic Complete Response (pCR) Rate (%) Overall
timeFrame: At time of surgery, up to a maximum of 261 days
measure: pCR Rate (%) by Baseline Histologic Subgroup
timeFrame: At time of surgery, up to a maximum of 261 days
measure: pCR Rate (%) by Baseline Tumor Location Subgroup
timeFrame: At time of surgery, up to a maximum of 261 days
measure: pCR Rate (%) by Steroid Use Subgroup
timeFrame: At time of surgery, up to a maximum of 261 days
measure: pCR Rate (%) by Surgery Subgroup
timeFrame: At time of surgery, up to a maximum of 261 days
Secondary outcomes:
measure: Rate (%) of R0 Resection Overall
timeFrame: At time of surgery, up to a maximum of 261 days
measure: Rate (%) of R0 Resection by Baseline Histologic Subgroup
timeFrame: At time of surgery, up to a maximum of 261 days
measure: Pathologic Stage at Time of Surgery
timeFrame: At time of surgery, up to a maximum of 261 days
measure: Radiographic/Metabolic Response to Neoadjuvant Treatment on Computed Tomography (CT)/CT-Positron Emission Tomography (PET) (CT-PET) Overall
timeFrame: At time of surgery, up to a maximum of 261 days, 3 and 6 months post-operatively, and End of Study Visit (maximum of 6 months post-operatively)
measure: Radiographic/Metabolic Response to Neoadjuvant Treatment on CT-PET by Baseline Histologic Subgroup
timeFrame: At time of surgery, up to a maximum of 261 days, 3 and 6 months post-operatively, and End of Study Visit (maximum of 6 months post-operatively)
measure: Radiographic/Metabolic Response to Neoadjuvant Treatment on CT-PET by Baseline Tumor Location Subgroup
timeFrame: At time of surgery, up to a maximum of 261 days, 3 and 6 months post-operatively, and End of Study Visit (maximum of 6 months post-operatively)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 20 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital (MGUH)
state: District of Columbia
city: New York
country: United States
facility: New York University
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References: