Resectable Esophageal CancerPhase 1/2NCT03490292
Avelumab With Chemoradiation for Stage II/III Resectable Esophageal and Gastroesophageal Cancer
A Phase 1/2 study testing Avelumab combined with Chemoradiation, Carboplatin and Paclitaxel in people with Resectable Esophageal Cancer and GastroEsophageal Cancer, run by University of Wisconsin, Madison at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Resectable Esophageal Cancer, GastroEsophageal Cancer
- What is being tested?
- Avelumab combined with Chemoradiation, Carboplatin and Paclitaxel
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 29 May 2018to 12 Jul 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Women who are nursing must discontinue breast-feeding prior to the enrollment in the trial
- Patient must be able and willing to comply with study procedures as per protocol
- Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures
Who cannot join
- 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)
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- 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
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel or avelumab, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3)
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. Patients with stable rate-controlled atrial fibrillation will be allowed to participate
- Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
- Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
About this study
Official title: Phase I/II Trial of Avelumab in Combination With Chemoradiation in the Treatment of Stage II/III Resectable Esophageal and Gastroesophageal Cancer
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
Read the detailed description
Background:
Neoadjuvant chemoradiation is part of the standard of care for patients with stage II and III resectable esophageal and gastroesophageal cancer. This approach is based on the results of a large randomized clinical trial (CROSS) that demonstrated superior survival in patients receiving neoadjuvant chemoradiotherapy followed by surgical resection compared to patients treated with surgery alone. Pathological complete response at the time of resection is strongly linked to better survival. However, with current strategies pathological complete response is achieved only in a minority (29%) of patients. Remaining patients, especially those with positive lymph nodes at the time of the resection, are at significant risk for recurrences. Five-year survival rate for these patients is only 37%, and overall survival is as low as 9 months for those with persistent lymph node disease. Among patients who develop recurrent disease, most present with distant metastases outside of the radiation field. This is not surprising since the accepted treatment paradigm for this disease does not target possible disseminated microscopic systemic disease. Hence, novel strategies are needed to improve outcomes of these patients. We propose conducting a phase I/II clinical trial evaluating a role of immune checkpoint inhibitor in combination with chemoradiotherapy and post-operatively in the management of resectable esophageal cancer.
Study Rationale:
- A number of preclinical and clinical studies demonstrated synergism between radiation and immunotherapy, suggesting that combining these approaches can enhance anti-tumor activity and increase treatment efficacy.
- Immune checkpoint inhibitors have demonstrated promising activity in a subset of patients with metastatic esophageal and gastric cancers. Moving these agents into neoadjuvant setting may increase the cure rate of this disease compared to the standard approach.
- Current neoadjuvant therapy does not target any potential microscopic disease outside of the radiation field since chemotherapy serves primarily as a radiation sensitizer. Immunotherapy treatment will target both local and systemic disease.
Hypothesis:
We hypothesize that co-administration of avelumab with chemoradiation will be well tolerated and will increase pathological complete response rate in resected tumor specimens. We hypothesize that avelumab treatment will also decrease the rates of disease recurrence.
Study Design:
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.
Objectives:
Primary: Evaluate the safety of avelumab in combination with chemoradiation in patients with resectable esophageal cancer and gastroesophageal receiving perioperative therapy.
Secondary: Obtain efficacy data and further safety data of the proposed drug combination in this patient population.
Exploratory objectives: The translational focus of the study will evaluate changes in tumor microenvironment that occur in response to radiation and immunotherapy.
Endpoints:
Part 1 - Primary endpoint: Establish safety and tolerability of the proposed treatment.
Part 2 - Primary Endpoint: Pathological complete response rate.
Part 2 - Secondary Endpoints:
- Safety and tolerability.
- Disease free survival.
- Incidence of surgical complications.
- Rate of R0 resection.
Number of centers \& patients: One center.
Part 1: total of 6 eligible patients will be accrued to evaluate the safety and tolerability of the proposed combination.
Part 2: 18 patients will be enrolled in the phase 2 portion of the trial.
Population:
Patients with histologically confirmed, potentially curable squamous-cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus and gastroesophagus who are candidates for neoadjuvant therapy and surgical resection.
Investigational drugs:
Avelumab (Provided by EMD Serono). IND information to be added as needed.
- Being tested
- Avelumab combined with Chemoradiation, Carboplatin, Paclitaxel, Radiation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Avelumab combined with ChemoradiationCombination product
Co-administration of avelumab with chemoradiation in pre-operative period.
CarboplatinDrug
Weekly Carboplatin (AUC2) [intravenous infusion on days 1, 8, 15, 22, \& 29]
PaclitaxelDrug
Weekly paclitaxel [intravenous infusion on days 1, 8, 15, 22, \& 29]
RadiationRadiation
Radiation therapy [23 fractions, M-F, estimated completion day 35]
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Combination Product: Avelumab combined with Chemoradiation; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Part 2 will further evaluate the safety of the studied drug combination, building on the observations from Part 1.
All patients who receive at least one dose of avelumab will be evaluated for toxicity. Toxicities observed will be summarized in terms of types and severities by Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 (see Adverse Events section).
Measured: 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
Part 2 will further evaluate the tolerability of the studied drug combination, building on the observations from Part 1.
Tolerability will be reported as the number of subjects who did or did not complete the planned treatment, including the reason they ended treatment early.
Measured: Up to 30 days post-avelumab of all participants (up to 4 months on study)
Number of Participants With Unexpected Surgical Complications
Measured: Following resection (80 -100 days) for all participants (up to approximately 5 months on study)
Rate of R0 Resection
R0 resection corresponds to resection for cure or complete remission.
Measured: Following pathology review post-resection (80 -100 days) for all participants (up to approximately 4 months on study)
Disease Free Survival
Disease free survival (DFS) will be defined as the number of days from the day of resection to the day a subject experiences an event of disease recurrence or death, whichever comes first. If a subject has not experienced an event of disease recurrence progression or death at the time of analysis, then the subject's data will be censored at the date of the last available evaluation. DFS will be summarized using point estimates of the median time to progression and the associated 95% confidence interval. The data will be presented graphically using Kaplan-Meier plots.
Measured: Up to 4 years post-resection for all participants
Estimated 1-year Recurrence Free Survival
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2018
- Study start29 May 2018
- Primary completion19 Jan 2022
- Study completion12 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Resectable Esophageal CancerStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nataliya Uboha, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03490292
- Sponsor's protocol ID
- UW17106
- Other IDs
- NCI-2018-00150, 2017-1491, A534260, SMPH\MEDICINE\HEM-ONC, Protocol Version 7/5/2021
- Status last verified
- Jul 2024
- First submitted
- 9 Feb 2018
- Last updated
- 26 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Avelumab in Combination With Chemoradiation in the Treatment of Stage II/III Resectable Esophageal and Gastroesophageal Cancer
- ClinicalTrials.gov ID
- NCT03490292
- Acronym / sponsor ID
- UW17106
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Study start
- 29 May 2018 (actual)
- Primary completion
- 19 Jan 2022 (actual)
- Study completion
- 12 Jul 2023 (actual)
- First posted
- 6 Apr 2018 (actual)
- Results
- Posted 26 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Background:
Neoadjuvant chemoradiation is part of the standard of care for patients with stage II and III resectable esophageal and gastroesophageal cancer. This approach is based on the results of a large randomized clinical trial (CROSS) that demonstrated superior survival in patients receiving neoadjuvant chemoradiotherapy followed by surgical resection compared to patients treated with surgery alone. Pathological complete response at the time of resection is strongly linked to better survival. However, with current strategies pathological complete response is achieved only in a minority (29%) of patients. Remaining patients, especially those with positive lymph nodes at the time of the resection, are at significant risk for recurrences. Five-year survival rate for these patients is only 37%, and overall survival is as low as 9 months for those with persistent lymph node disease. Among patients who develop recurrent disease, most present with distant metastases outside of the radiation field. This is not surprising since the accepted treatment paradigm for this disease does not target possible disseminated microscopic systemic disease. Hence, novel strategies are needed to improve outcomes of these patients. We propose conducting a phase I/II clinical trial evaluating a role of immune checkpoint inhibitor in combination with chemoradiotherapy and post-operatively in the management of resectable esophageal cancer.
Study Rationale:
- A number of preclinical and clinical studies demonstrated synergism between radiation and immunotherapy, suggesting that combining these approaches can enhance anti-tumor activity and increase treatment efficacy.
- Immune checkpoint inhibitors have demonstrated promising activity in a subset of patients with metastatic esophageal and gastric cancers. Moving these agents into neoadjuvant setting may increase the cure rate of this disease compared to the standard approach.
- Current neoadjuvant therapy does not target any potential microscopic disease outside of the radiation field since chemotherapy serves primarily as a radiation sensitizer. Immunotherapy treatment will target both local and systemic disease.
Hypothesis:
We hypothesize that co-administration of avelumab with chemoradiation will be well tolerated and will increase pathological complete response rate in resected tumor specimens. We hypothesize that avelumab treatment will also decrease the rates of disease recurrence.
Study Design:
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.
Objectives:
Primary: Evaluate the safety of avelumab in combination with chemoradiation in patients with resectable esophageal cancer and gastroesophageal receiving perioperative therapy.
Secondary: Obtain efficacy data and further safety data of the proposed drug combination in this patient population.
Exploratory objectives: The translational focus of the study will evaluate changes in tumor microenvironment that occur in response to radiation and immunotherapy.
Endpoints:
Part 1 - Primary endpoint: Establish safety and tolerability of the proposed treatment.
Part 2 - Primary Endpoint: Pathological complete response rate.
Part 2 - Secondary Endpoints:
- Safety and tolerability.
- Disease free survival.
- Incidence of surgical complications.
- Rate of R0 resection.
Number of centers \& patients: One center.
Part 1: total of 6 eligible patients will be accrued to evaluate the safety and tolerability of the proposed combination.
Part 2: 18 patients will be enrolled in the phase 2 portion of the trial.
Population:
Patients with histologically confirmed, potentially curable squamous-cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus and gastroesophagus who are candidates for neoadjuvant therapy and surgical resection.
Investigational drugs:
Avelumab (Provided by EMD Serono). IND information to be added as needed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Run-In Phase | Experimental | Combination Product: Avelumab combined with Chemoradiation, Drug: Carboplatin, Drug: Paclitaxel, Radiation: Radiation6 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. |
| Expansion Cohort | Experimental | Combination Product: Avelumab combined with Chemoradiation, Drug: Carboplatin, Drug: Paclitaxel, Radiation: RadiationFollowing 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (19 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Avelumab combined with ChemoradiationCo-administration of avelumab with chemoradiation in pre-operative period. | Combination product | Expansion Cohort, Run-In Phase |
| CarboplatinWeekly Carboplatin (AUC2) [intravenous infusion on days 1, 8, 15, 22, \& 29] | Drug | Expansion Cohort, Run-In Phase |
| PaclitaxelWeekly paclitaxel [intravenous infusion on days 1, 8, 15, 22, \& 29] | Drug | Expansion Cohort, Run-In Phase |
| RadiationRadiation therapy [23 fractions, M-F, estimated completion day 35] | Radiation | Expansion Cohort, Run-In Phase |
Primary outcome
Number of Participants With Dose Limiting Toxicity
Time frame: Up to 4 weeks post-resection (up to approximately 4 months on study) of all Run-In Phase participants
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.
Number of Participants With Pathological Complete Response
Time frame: Post-resection (80-100 days) pathology review for all participants (up to approximately 4 months on study)
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.
6 secondary outcomes
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3
Time frame: 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
Time frame: Up to 30 days post-avelumab of all participants (up to 4 months on study)
Number of Participants With Unexpected Surgical Complications
Time frame: Following resection (80 -100 days) for all participants (up to approximately 5 months on study)
Rate of R0 Resection
Time frame: Following pathology review post-resection (80 -100 days) for all participants (up to approximately 4 months on study)
Disease Free Survival
Time frame: Up to 4 years post-resection for all participants
Estimated 1-year Recurrence Free Survival
Time frame: up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UW Carbone Cancer Center Home PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nataliya Uboha principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Avelumab combined with Chemoradiation, Carboplatin and Paclitaxel in people with Resectable Esophageal Cancer and GastroEsophageal Cancer, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicity (time frame: Up to 4 weeks post-resection (up to approximately 4 months on study) of all Run-In Phase participants). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2024.