Avelumab With Chemoradiation for Stage II/III Resectable Esophageal and Gastroesophageal Cancer

NCT03490292 | Completed Phase 1 Results DMC FDA Drug

• 6 other identifiers: UW17106NCI-2018-001502017-1491A534260SMPH\MEDICINE\HEM-ONCProtocol Version 7/5/2021
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 2 part Phase I/II clinical trial evaluating the safety, tolerability and efficacy of avelumab in combination with chemoradiation in patients with resectable esophageal and gastroesophageal cancer. Part 1: This is the run-in phase of the trial. This portion will determine the safety and tolerability of avelumab in combination with chemoradiotherapy in 6 patients. The proposed combination will be considered as safe if dose limiting toxicities are observed in at most 1 patient. Part 2: This is a Phase 2 portion of the trial, which will evaluate the efficacy of the proposed treatment regimen in patients with stage II/III resectable esophageal and gastroesophageal cancer

Conditions

Resectable Esophageal Cancer; GastroEsophageal Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicity

  A total number of 6 subjects will be enrolled during the run-in phase of the trial. A sample size of 6 is sufficient to estimate the true dose limiting toxicity rate of the proposed avelumab/chemoradiation therapy with adequate accuracy.The proposed treatment combination will be considered as safe if dose limiting toxicities are observed in at most 1 patient.

  Up to 4 weeks post-resection (up to approximately 4 months on study) of all Run-In Phase participants

• Number of Participants With Pathological Complete Response

  Pathologic compete response (pCR) is defined as an absence of any viable tumor at microscopic examination of the primary tumor and any lymph nodes sampled after surgery following neoadjuvant therapy. Participants with invalid/missing pCR assessments will be defined as non-responders. The number and frequency of patients with a pCR will be summarized in tabular format.

  Post-resection (80-100 days) pathology review for all participants (up to approximately 4 months on study)

Secondary Outcomes (6)

• Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3

  Up to 30 days post-avelumab of all (up to 4 months on study)

• Number of Participants Who Did or Did Not Complete Planned Treatment

  Up to 30 days post-avelumab of all participants (up to 4 months on study)

• Number of Participants With Unexpected Surgical Complications

  Following resection (80 -100 days) for all participants (up to approximately 5 months on study)

• Rate of R0 Resection

  Following pathology review post-resection (80 -100 days) for all participants (up to approximately 4 months on study)

• Disease Free Survival

  Up to 4 years post-resection for all participants

Study Arms (2)

Run-In Phase

EXPERIMENTAL

6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a dose-limiting toxicity (DLT) during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment.

Combination Product: Avelumab combined with Chemoradiation; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation

Expansion Cohort

EXPERIMENTAL

Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).

Combination Product: Avelumab combined with Chemoradiation; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation

Interventions

Avelumab combined with Chemoradiation COMBINATION_PRODUCT

Co-administration of avelumab with chemoradiation in pre-operative period.

Expansion Cohort; Run-In Phase

Carboplatin DRUG

Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\]

Expansion Cohort; Run-In Phase

Paclitaxel DRUG

Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\]

Expansion Cohort; Run-In Phase

Radiation RADIATION

Radiation therapy \[23 fractions, M-F, estimated completion day 35\]

Expansion Cohort; Run-In Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed, potentially curable squamous-cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus and gastroesophagus (Siewert type 1-3)
• Locoregional disease with clinical stage of T1N1 or T2-3N0-2
• No clinical evidence of metastatic spread. Staging should include endoscopic ultrasound and positron emission tomography/computed tomography (PET/CT) as recommended by National Comprehensive Cancer Network (NCCN) guidelines. PET/CT should be performed within 3 weeks of signing informed consent
• Age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Subjects must be deemed to be potential surgical candidates by an evaluating surgeon
• Adequate organ function:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Hemoglobin ≥ 9 g/dL (transfusions allowed)
• Platelets ≥ 100 x 109/L
• Aspartate transaminase/Alanine transaminase (AST/ALT) ≤ 2.5 x ULN
• Total serum bilirubin of ≤1.5 x institutional upper limit of normal (ULN)
• Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula
• Female patients of childbearing potential must have a negative pregnancy test (urine or serum) within 21 days prior to the start of the study drug treatment and must agree to use adequate birth control if conception is possible during the study and up to 30 days after the completion of adjuvant therapy
• Male patients must agree to use adequate birth control during the study and up to 30 days after the last avelumab dose

You may not qualify if:

• Prior history of radiation to the mediastinum
• Diagnosis of cervical esophageal carcinoma
• Other active malignancy within the last 3 years (except for non-melanoma skin cancer, a non-invasive/in situ cancer, or indolent non metastatic Gleason 6 prostate cancer)
• Subjects with an active or known autoimmune disease. Subjects with type I diabetes mellitus, hypo- or hyperthyroidism only requiring hormone replacement/suppression, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic immunosuppressive treatment are eligible
• Current use of immunosuppressive medication, except for the following:
• intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
• systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Active infection requiring systemic therapy at the time of study treatment initiation
• Prior organ transplantation including allogenic stem-cell transplantation
• Known history of testing positive for HIV or known immunodeficiency syndrome
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
• Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines
• Major surgery within prior 4 weeks of treatment initiation (the surgical incision should be fully healed prior to all neoadjuvant treatment initiation)
• Any prior anticancer therapy for esophageal cancer

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Links

• UW Carbone Cancer Center Home Page

MeSH Terms

Interventions

Chemoradiotherapy; Carboplatin; Paclitaxel; Radiation

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Physical Phenomena

Results Point of Contact

• Title: Nataliya Uboha, MD, PhD
• Organization: UW Carbone Cancer Center

nvuboha@medicine.wisc.edu

(608) 265-9966

Study Officials

• Nataliya Uboha

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a two-part phase 1/2 clinical trial conducted in one center. Part 1. Run-in phase to assess the safety and tolerability of avelumab in combination with chemoradiation. Will enroll 6 patients, after which accrual will be stopped temporarily while safety data is being obtained. Part 2. An open-label phase 2 study. Part 2 will obtain further safety data of the proposed drug combination and will evaluate the anti-tumor efficacy of perioperative avelumab and chemoradiation in this patient population. Will enroll 18 additional patients. Each phase of the study will have a 21-day screening period, treatment procedures (neoadjuvant therapy, resection and adjuvant therapy), and active surveillance for a year after the completion of adjuvant therapy. After active surveillance visit at 12 months post treatment completion, survival data and disease status will be collected via phone calls or medical record review every 6 months during the following 3 years.

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: April 6, 2018
• Study Start: May 29, 2018
• Primary Completion: January 19, 2022
• Study Completion: July 12, 2023
• Last Updated: July 26, 2024
• Results First Posted: July 26, 2024

Record last verified: 2024-07

Locations

US (1)