Esophageal CancerPhase 2NCT03223662
Metabolomic and BH3 Profiling of Esophageal Cancers: Identification of Novel Assessment Methods of Treatment Response for Precision Therapy
A Phase 2 study testing Chemoradiotherapy and Esophagectomy in people with Esophageal Cancer and Esophageal Adenocarcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: The number of patients with esophageal cancer keeps rising. For many patients, a combination of surgery, chemotherapy, and radiation is necessary to completely treat the disease. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Esophageal Cancer, Esophageal Adenocarcinoma, Esophageal Squamous Cell Cancer
- What is being tested?
- Chemoradiotherapy and Esophagectomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2017to 27 Jul 2018
- Phase
- Phase 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed esophageal adenocarcinoma (EAC) or esophageal squamous cell carcinoma (ESCC).
- Disease should be deemed resectable by pre-operative computed tomography (CT) and/or positron-emission tomography (PET) scans and the patient should be operable based on surgeon assessment.
- Patients willing to complete neoadjuvant chemoradiotherapy (nCRT) per standard of care followed by esophagectomy. Patients will be treated under protocol 04-C0165.
- 18 years of age or older.
- Able to understand and sign the Informed Consent Document.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
Show all 12Show fewer
- Patients must have organ and marrow function that is not prohibitive of surgical resection as defined below:
- leukocytes greater than or equal to 3,000/mcL
- absolute neutrophil count greater than or equal to 1,500/mcL
- platelets greater than or equal to 50,000/mcL
- nCRT used in this study is potentially dangerous for developing human fetus. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration and 6 months post chemoradiotherapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Women must have a negative urine pregnancy test OR be post-menopausal for at least 2 years OR patient has had a hysterectomy
Who cannot join
- Patients in which nCRT followed by surgery is not the appropriate management:
- Early stage disease that requires local therapy without chemoradiotherapy (CRT).
- Patients with metastatic disease.
- Patients in which biopsy prior to starting nCRT is not obtainable.
- Patients who previously received neoadjuvant chemotherapy
- Concomitant medical problems in the opinion of physician that would place the patient at unacceptable risk for a major surgical procedure.
Show all 9Show fewer
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, heart failure, hepatic disease that prohibits administration of neoadjuvant therapy or surgery.
- Women who are pregnant or breastfeeding because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
- Patients with a diagnosis of another malignancy that is either active or in remission less than five years. Basal cell and squamous cell carcinoma of the skin are not contraindications to this protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
The number of patients with esophageal cancer keeps rising. For many patients, a combination of surgery, chemotherapy, and radiation is necessary to completely treat the disease. Usually, patients receive chemotherapy and radiation at the same time followed by surgery to remove the part of the esophagus with the tumor (Neoadjuvant chemoradiotherapy (nCRT)). Researchers want to learn how to make this treatment more effective.
Read more
Objective:
To see if biopsies before treatment can show which patients will do the best with a combination of chemotherapy, radiation, and surgery.
Eligibility:
Adults at least 18 years old with esophageal adenocarcinoma or squamous cell carcinoma who should be treated with chemotherapy, radiation, and surgery.
Design:
Patients will undergo standard testing that is routine for all patients with this disease. These tests include:
Medical history
Physical exam with activity and nutritional assessment
Standard lab tests
Imaging studies including a computerized axial tomography (CAT) scan and positron-emission tomography (PET) scan
Breathing test into a machine to measure size and function of lungs.
Biopsy for a small sample of tumor is removed by esophagogastroduodenoscopy (EGD): A tube inserted into the mouth under anesthesia
Endoscopic ultrasound is performed in some but not all patients.
Patients will have nCRT at the clinic or with their local doctor.
In 6 -12 weeks after nCRT, patients will undergo surgery with:
- A robotically-assisted, minimally-invasive esophagectomy
- Or, a traditional, open approach.
After surgery, patients are usually in the hospital for 2 weeks and have a feeding tube for at least 2 weeks and potentially longer until they are eating enough to not lose weight.
Patients will return for follow-up visits with labs and CAT scans every 6 months for the first two years then every year afterwards.
Read the detailed description
Background:
- The incidence of esophageal cancer continues to increase with an estimated 16,900 new cases and 15,700 deaths in 2016. Esophageal adenocarcinoma (EAC) is the dominant histology in the United States and accounts for the rising incidence; the incidence of esophageal squamous cell cancer (ESCC) remains stable.
- Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is now a standard approach for locally advanced, operable esophageal cancer.
- A survival advantage compared to surgery alone was demonstrated in the phase III Chemo
Radiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial.
- Patients who experience a pathological complete response (pCR) following neoadjuvant therapy are most likely to have long-term survival.
- Presently, accurate assessment of pathologic response requires esophagectomy. Positron-emissions tomography (fludeoxyglucose (FDG-PET)) and endoscopic evaluation with biopsies fail to detect cancer in a significant percentage of patients with residual disease following neoadjuvant therapy.
- Currently there are no validated tissue or serologic biomarkers which can be used to guide surgical management of esophageal cancer patients based on response to nCRT.
Primary Objective:
-To determine whether a metabolomic signature in tumor, blood, or urine or whether BH3 profiling of pre-neoadjuvant tumor biopsies correlates with the outcome of pathological complete response after neoadjuvant chemoradiotherapy for patients with esophageal adenocarcinoma or squamous cell carcinoma.
Eligibility:
-Patients with locally-advanced, histologically confirmed EAC or ESCC who are candidates for nCRT and esophagectomy.
Design:
- Patients will receive standard of care nCRT either at the National Cancer Institute (NCI) or at referring institutions.
- Specimens of plasma, urine, and esophageal tumor with matched normal esophagus will be obtained before neoadjuvant therapy for metabolomic profiling and BH3 profiling.
Blood, urine, normal esophagus, and tumor (if present) will be obtained after neoadjuvant therapy.
- Patients will undergo an esophagectomy as a robotically-assisted, minimally-invasive esophagectomy (RAMIE) or a traditional open approach for contraindications to minimally-invasive approaches or based on institutional expertise.
- Analysis will be performed to determine if pathological complete response (pCR) after chemoradiotherapy (CRT) correlates with pretreatment metabolomic signatures or BH3 profiling in tumor, blood or urine.
- Patients with EAC and ESCC will be evaluated independently.
- The accrual ceiling will be set to 120 patients for the entire study - 80 patients for EAC and 40 patients for ESCC to allow for unevaluable patients. The accrual is expected to be completed in 4 years.
- Conditions
- Esophageal Cancer, Esophageal Adenocarcinoma, Esophageal Squamous Cell Cancer, Esophageal Neoplasms, Squamous Cell Carcinoma
- Being tested
- Chemoradiotherapy, Esophagectomy
- Keywords
- Neoadjuvant Chemoradiotherapy (nCRT), Esophagectomy, Tissue or serologic biomarkers
- Medical subject headings
- Esophageal Neoplasms, Adenocarcinoma Of Esophagus, Esophageal Squamous Cell Carcinoma, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChemoradiotherapyOther
Chemotherapy: Carboplatin (AUC=2)x5 and Paclitaxel (50 mg/m(2))x5 for two cycles. Radiation: a total dose of 40.4 Gray (Gy) will be given in 23 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy.
EsophagectomyProcedure or surgery
Minimally-invasive esophagectomy (RAMIE) or traditional open approach if necessary.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant Chemoradiotherapy and esophagectomy | Other | Standard of care neoadjuvant chemoradiotherapy (nCRT) and esophagectomy Receives: Other: Chemoradiotherapy; Procedure: Esophagectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolomic Signature in Tumor, Blood, or Urine and Outcome of Pathological Complete Response After Neoadjuvant Chemoradiotherapy in Patients With Esophageal Adenocarcinoma or Squamous Cell Carcinoma
Specimens of normal esophagus, esophageal tumors, blood, or urine will be analyzed to determine specific signatures and outcome of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal adenocarcinoma or squamous cell carcinoma. Response will be defined by the Mandard Score. Major response with no viable tumor (Grade 1) and <10% viable tumor (Grade 2) versus non major response of >10% viable tumor (Grade 3-5) as assessed by final pathology. Grade 1-2 is better survival than Grade 3-5.
Measured: After neoadjuvant therapy >4 weeks but prior to surgery
BH3 Profiling of Pre-neoadjuvant Tumor Biopsy and Outcome of Pathological Complete Response After Neoadjuvant Chemoradiotherapy in Patients With Esophageal Adenocarcinoma or Squamous Cell Carcinoma
Two tumor samples and two normal esophagus samples will be obtained for BH3 profiling of pre-neoadjuvant tumor biopsy and outcome of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal adenocarcinoma or squamous cell carcinoma. Response will be defined by the Mandard Score. Major response with no viable tumor (Grade 1) and <10% viable tumor (Grade 2) versus non major response of >10% viable tumor (Grade 3-5) as assessed by final pathology. Grade 1-2 is better survival than Grade 3-5.
Measured: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery
Secondary outcomes (5)
Metabolomic Profiles and B-cell Lymphoma (Bcl-2) Homology Domain-3 (BH-3) Profiling in Resectable Esophageal Adenocarcinomas (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) Treated With Neoadjuvant Chemoradiotherapy (nCRT)
Evaluation of metabolomic profiles and Bcl-2 homology domain-3 (BH-3) profiling in resectable esophageal adenocarcinomas (EAC) and esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT)
Measured: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery
Metabolomic Signatures or BH3 Profiling in Tumor, Blood, or Urine of Esophageal Adenocarcinoma (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) With Major Responses (Mandard Score of 1 and 2) Versus Minimal Response (Mandard Score 3-5)
Specimens of tumor, blood, or urine will be obtained to determine metabolomic signatures or BH3 profiling in tumor, blood, or urine of EAC and ESCC with major responses (Mandard score of 1 and 2) versus minimal response (Mandard score 3-5). Grade 1-2 is better survival than Grade 3-5.
Measured: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery
Tumor Protein 53 (p53) Mutational Status and the Metabolomic Profiles
One tumor sample and one normal esophagus sample will be obtained. p53 mutational analysis will be performed to determine mutational status and the metabolomic profiles .
Measured: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery
Disease-free Survival in Esophageal Adenocarcinoma (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) Patients Undergoing Neoadjuvant Chemoradiotherapy (nCRT) and Esophagectomy
Disease-free survival is defined as the appearance of any new lesion that is likely metastatic or locally-recurrent esophageal cancer and will be assessed from the time of esophagectomy until development of metastatic disease or death, whichever comes first
Measured: From the time of esophagectomy until development of metastatic disease or death, whichever comes first
Overall Survival (OS) in Esophageal Adenocarcinoma (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) Patients Undergoing Neoadjuvant Chemoradiotherapy (nCRT) and Esophagectomy
Overall survival is defined as the time from treatment start date until date of death or date last known alive.
Measured: From treatment start date until date of death or date last known alive.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start31 Oct 2017
- Primary completion27 Jul 2018
- Study completion27 Jul 2018
Why it stopped: Principal Investigator left the NIH.
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.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Esophageal CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Caryn Steakley, R.N., National Institutes of Health Clinical Center (CC)
- Investigators
- Robert T Ripley, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03223662
- Sponsor's protocol ID
- 170135
- Other IDs
- 17-C-0135
- Status last verified
- Oct 2018
- First submitted
- 19 Jul 2017
- Last updated
- 30 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Piessen G, Messager M, Mirabel X, Briez N, Robb WB, Adenis A, Mariette C. Is there a role for surgery for patients with a complete clinical response after chemoradiation for esophageal cancer? An intention-to-treat case-control study. Ann Surg. 2013 Nov;258(5):793-9; discussion 799-800. doi: 10.1097/SLA.0000000000000228.
PubMed 24096755Stiles BM, Salzler G, Jorgensen A, Nasar A, Paul S, Lee PC, Port JL, Altorki NK. Complete metabolic response is not uniformly predictive of complete pathologic response after induction therapy for esophageal cancer. Ann Thorac Surg. 2013 Nov;96(5):1820-5. doi: 10.1016/j.athoracsur.2013.05.027. Epub 2013 Jul 26.
PubMed 23895888Shaikh T, Ruth K, Scott WJ, Burtness BA, Cohen SJ, Konski AA, Cooper HS, Astsaturov I, Meyer JE. Increased time from neoadjuvant chemoradiation to surgery is associated with higher pathologic complete response rates in esophageal cancer. Ann Thorac Surg. 2015 Jan;99(1):270-6. doi: 10.1016/j.athoracsur.2014.08.033. Epub 2014 Nov 18.
PubMed 25440267Taylor Ripley R, Surman DR, Diggs LP, Trepel JB, Lee MJ, Ryan J, Davis JL, Steinberg SM, Hernandez JM, Hoang C, Kenney CM, Bond CD, Kunst TF, Letai A, Schrump DS. Metabolomic and BH3 profiling of esophageal cancers: novel assessment methods for precision therapy. BMC Gastroenterol. 2018 Jun 22;18(1):94. doi: 10.1186/s12876-018-0823-x.
PubMed 29933761
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolomic and BH3 Profiling of Esophageal Cancers: Identification of Novel Assessment Methods of Treatment Response for Precision Therapy
- ClinicalTrials.gov ID
- NCT03223662
- Acronym / sponsor ID
- 170135
- Conditions
- Esophageal Cancer, Esophageal Adenocarcinoma, Esophageal Squamous Cell Cancer, Esophageal Neoplasms, Squamous Cell Carcinoma
- Keywords
- Neoadjuvant Chemoradiotherapy (nCRT), Esophagectomy, Tissue or serologic biomarkers
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Principal Investigator left the NIH.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- 27 Jul 2018 (actual)
- Study completion
- 27 Jul 2018 (actual)
- First posted
- 21 Jul 2017 (actual)
- Results
- Posted 30 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
The number of patients with esophageal cancer keeps rising. For many patients, a combination of surgery, chemotherapy, and radiation is necessary to completely treat the disease. Usually, patients receive chemotherapy and radiation at the same time followed by surgery to remove the part of the esophagus with the tumor (Neoadjuvant chemoradiotherapy (nCRT)). Researchers want to learn how to make this treatment more effective.
Objective:
To see if biopsies before treatment can show which patients will do the best with a combination of chemotherapy, radiation, and surgery.
Eligibility:
Adults at least 18 years old with esophageal adenocarcinoma or squamous cell carcinoma who should be treated with chemotherapy, radiation, and surgery.
Design:
Patients will undergo standard testing that is routine for all patients with this disease. These tests include:
Medical history
Physical exam with activity and nutritional assessment
Standard lab tests
Imaging studies including a computerized axial tomography (CAT) scan and positron-emission tomography (PET) scan
Breathing test into a machine to measure size and function of lungs.
Biopsy for a small sample of tumor is removed by esophagogastroduodenoscopy (EGD): A tube inserted into the mouth under anesthesia
Endoscopic ultrasound is performed in some but not all patients.
Patients will have nCRT at the clinic or with their local doctor.
In 6 -12 weeks after nCRT, patients will undergo surgery with:
- A robotically-assisted, minimally-invasive esophagectomy
- Or, a traditional, open approach.
After surgery, patients are usually in the hospital for 2 weeks and have a feeding tube for at least 2 weeks and potentially longer until they are eating enough to not lose weight.
Patients will return for follow-up visits with labs and CAT scans every 6 months for the first two years then every year afterwards.
Detailed description
Background:
- The incidence of esophageal cancer continues to increase with an estimated 16,900 new cases and 15,700 deaths in 2016. Esophageal adenocarcinoma (EAC) is the dominant histology in the United States and accounts for the rising incidence; the incidence of esophageal squamous cell cancer (ESCC) remains stable.
- Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is now a standard approach for locally advanced, operable esophageal cancer.
- A survival advantage compared to surgery alone was demonstrated in the phase III Chemo
Radiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial.
- Patients who experience a pathological complete response (pCR) following neoadjuvant therapy are most likely to have long-term survival.
- Presently, accurate assessment of pathologic response requires esophagectomy. Positron-emissions tomography (fludeoxyglucose (FDG-PET)) and endoscopic evaluation with biopsies fail to detect cancer in a significant percentage of patients with residual disease following neoadjuvant therapy.
- Currently there are no validated tissue or serologic biomarkers which can be used to guide surgical management of esophageal cancer patients based on response to nCRT.
Primary Objective:
-To determine whether a metabolomic signature in tumor, blood, or urine or whether BH3 profiling of pre-neoadjuvant tumor biopsies correlates with the outcome of pathological complete response after neoadjuvant chemoradiotherapy for patients with esophageal adenocarcinoma or squamous cell carcinoma.
Eligibility:
-Patients with locally-advanced, histologically confirmed EAC or ESCC who are candidates for nCRT and esophagectomy.
Design:
- Patients will receive standard of care nCRT either at the National Cancer Institute (NCI) or at referring institutions.
- Specimens of plasma, urine, and esophageal tumor with matched normal esophagus will be obtained before neoadjuvant therapy for metabolomic profiling and BH3 profiling.
Blood, urine, normal esophagus, and tumor (if present) will be obtained after neoadjuvant therapy.
- Patients will undergo an esophagectomy as a robotically-assisted, minimally-invasive esophagectomy (RAMIE) or a traditional open approach for contraindications to minimally-invasive approaches or based on institutional expertise.
- Analysis will be performed to determine if pathological complete response (pCR) after chemoradiotherapy (CRT) correlates with pretreatment metabolomic signatures or BH3 profiling in tumor, blood or urine.
- Patients with EAC and ESCC will be evaluated independently.
- The accrual ceiling will be set to 120 patients for the entire study - 80 patients for EAC and 40 patients for ESCC to allow for unevaluable patients. The accrual is expected to be completed in 4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Chemoradiotherapy and esophagectomy | Other | Other: Chemoradiotherapy, Procedure: EsophagectomyStandard of care neoadjuvant chemoradiotherapy (nCRT) and esophagectomy |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients must have histologically confirmed esophageal adenocarcinoma (EAC) or esophageal squamous cell carcinoma (ESCC).
- Disease should be deemed resectable by pre-operative computed tomography (CT) and/or positron-emission tomography (PET) scans and the patient should be operable based on surgeon assessment.
- Patients willing to complete neoadjuvant chemoradiotherapy (nCRT) per standard of care followed by esophagectomy. Patients will be treated under protocol 04-C0165.
- 18 years of age or older.
- Able to understand and sign the Informed Consent Document.
Key exclusion criteria (9 listed)
- Patients in which nCRT followed by surgery is not the appropriate management:
- Patients in which biopsy prior to starting nCRT is not obtainable.
- Patients who previously received neoadjuvant chemotherapy
- Concomitant medical problems in the opinion of physician that would place the patient at unacceptable risk for a major surgical procedure.
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, heart failure, hepatic disease that prohibits administration of neoadjuvant therapy or surgery.
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 |
|---|---|---|
| ChemoradiotherapyChemotherapy: Carboplatin (AUC=2)x5 and Paclitaxel (50 mg/m(2))x5 for two cycles. Radiation: a total dose of 40.4 Gray (Gy) will be given in 23 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy. | Other | Neoadjuvant Chemoradiotherapy and esophagectomy |
| EsophagectomyMinimally-invasive esophagectomy (RAMIE) or traditional open approach if necessary. | Procedure or surgery | Neoadjuvant Chemoradiotherapy and esophagectomy |
Primary outcome
Metabolomic Signature in Tumor, Blood, or Urine and Outcome of Pathological Complete Response After Neoadjuvant Chemoradiotherapy in Patients With Esophageal Adenocarcinoma or Squamous Cell Carcinoma
Time frame: After neoadjuvant therapy >4 weeks but prior to surgery
Specimens of normal esophagus, esophageal tumors, blood, or urine will be analyzed to determine specific signatures and outcome of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal adenocarcinoma or squamous cell carcinoma. Response will be defined by the Mandard Score. Major response with no viable tumor (Grade 1) and <10% viable tumor (Grade 2) versus non major response of >10% viable tumor (Grade 3-5) as assessed by final pathology. Grade 1-2 is better survival than Grade 3-5.
BH3 Profiling of Pre-neoadjuvant Tumor Biopsy and Outcome of Pathological Complete Response After Neoadjuvant Chemoradiotherapy in Patients With Esophageal Adenocarcinoma or Squamous Cell Carcinoma
Time frame: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery
Two tumor samples and two normal esophagus samples will be obtained for BH3 profiling of pre-neoadjuvant tumor biopsy and outcome of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal adenocarcinoma or squamous cell carcinoma. Response will be defined by the Mandard Score. Major response with no viable tumor (Grade 1) and <10% viable tumor (Grade 2) versus non major response of >10% viable tumor (Grade 3-5) as assessed by final pathology. Grade 1-2 is better survival than Grade 3-5.
5 secondary outcomes
Metabolomic Profiles and B-cell Lymphoma (Bcl-2) Homology Domain-3 (BH-3) Profiling in Resectable Esophageal Adenocarcinomas (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) Treated With Neoadjuvant Chemoradiotherapy (nCRT)
Time frame: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery
Metabolomic Signatures or BH3 Profiling in Tumor, Blood, or Urine of Esophageal Adenocarcinoma (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) With Major Responses (Mandard Score of 1 and 2) Versus Minimal Response (Mandard Score 3-5)
Time frame: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery
Tumor Protein 53 (p53) Mutational Status and the Metabolomic Profiles
Time frame: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery
Disease-free Survival in Esophageal Adenocarcinoma (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) Patients Undergoing Neoadjuvant Chemoradiotherapy (nCRT) and Esophagectomy
Time frame: From the time of esophagectomy until development of metastatic disease or death, whichever comes first
Overall Survival (OS) in Esophageal Adenocarcinoma (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) Patients Undergoing Neoadjuvant Chemoradiotherapy (nCRT) and Esophagectomy
Time frame: From treatment start date until date of death or date last known alive.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24096755Piessen G, Messager M, Mirabel X, Briez N, Robb WB, Adenis A, Mariette C. Is there a role for surgery for patients with a complete clinical response after chemoradiation for esophageal cancer? An intention-to-treat case-control study. Ann Surg. 2013 Nov;258(5):793-9; discussion 799-800. doi: 10.1097/SLA.0000000000000228.
- Background: PubMed 23895888Stiles BM, Salzler G, Jorgensen A, Nasar A, Paul S, Lee PC, Port JL, Altorki NK. Complete metabolic response is not uniformly predictive of complete pathologic response after induction therapy for esophageal cancer. Ann Thorac Surg. 2013 Nov;96(5):1820-5. doi: 10.1016/j.athoracsur.2013.05.027. Epub 2013 Jul 26.
- Background: PubMed 25440267Shaikh T, Ruth K, Scott WJ, Burtness BA, Cohen SJ, Konski AA, Cooper HS, Astsaturov I, Meyer JE. Increased time from neoadjuvant chemoradiation to surgery is associated with higher pathologic complete response rates in esophageal cancer. Ann Thorac Surg. 2015 Jan;99(1):270-6. doi: 10.1016/j.athoracsur.2014.08.033. Epub 2014 Nov 18.
- Derived from this study: PubMed 29933761Taylor Ripley R, Surman DR, Diggs LP, Trepel JB, Lee MJ, Ryan J, Davis JL, Steinberg SM, Hernandez JM, Hoang C, Kenney CM, Bond CD, Kunst TF, Letai A, Schrump DS. Metabolomic and BH3 profiling of esophageal cancers: novel assessment methods for precision therapy. BMC Gastroenterol. 2018 Jun 22;18(1):94. doi: 10.1186/s12876-018-0823-x.
- Individual participant dataSharing planned: No
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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.
Robert T Ripley principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chemoradiotherapy and Esophagectomy in people with Esophageal Cancer and Esophageal Adenocarcinoma, run by National Cancer Institute (NCI) 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 12 inclusion and 9 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: stopped early, as of the sponsor's last update on 30 Oct 2018. 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 phase mean?
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 30 Oct 2018). 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?
Metabolomic Signature in Tumor, Blood, or Urine and Outcome of Pathological Complete Response After Neoadjuvant Chemoradiotherapy in Patients With Esophageal Adenocarcinoma or Squamous Cell Carcinoma (time frame: After neoadjuvant therapy >4 weeks but prior to surgery). 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?
On the ClinicalTrials.gov record for NCT03223662, which also lists 4 linked publications.
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 30 Oct 2018.