Trial Outcomes & Findings for Metabolomic and BH3 Profiling of Esophageal Cancers: Identification of Novel Assessment Methods of Treatment Response for Precision Therapy (NCT NCT03223662)

NCT ID: NCT03223662

Last Updated: 2018-10-30

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

After neoadjuvant therapy >4 weeks but prior to surgery

Results posted on

2018-10-30

Participant Flow

Participant milestones

Participant milestones
Measure
Neoadjuvant Chemoradiotherapy and Esophagectomy
Standard of care neoadjuvant chemoradiotherapy (nCRT) and esophagectomy Chemoradiotherapy: 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. Esophagectomy: Minimally-invasive esophagectomy (RAMIE) or traditional open approach if necessary.
Overall Study
STARTED
2
Overall Study
COMPLETED
0
Overall Study
NOT COMPLETED
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Neoadjuvant Chemoradiotherapy and Esophagectomy
Standard of care neoadjuvant chemoradiotherapy (nCRT) and esophagectomy Chemoradiotherapy: 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. Esophagectomy: Minimally-invasive esophagectomy (RAMIE) or traditional open approach if necessary.
Overall Study
Physician Decision
1
Overall Study
Study closure
1

Baseline Characteristics

Metabolomic and BH3 Profiling of Esophageal Cancers: Identification of Novel Assessment Methods of Treatment Response for Precision Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Neoadjuvant Chemoradiotherapy and Esophagectomy
n=2 Participants
Standard of care neoadjuvant chemoradiotherapy (nCRT) and esophagectomy Chemoradiotherapy: 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. Esophagectomy: Minimally-invasive esophagectomy (RAMIE) or traditional open approach if necessary.
Age, Categorical
<=18 years
0 Participants
n=99 Participants
Age, Categorical
Between 18 and 65 years
2 Participants
n=99 Participants
Age, Categorical
>=65 years
0 Participants
n=99 Participants
Age, Continuous
58.55 years
STANDARD_DEVIATION 5.3 • n=99 Participants
Sex: Female, Male
Female
0 Participants
n=99 Participants
Sex: Female, Male
Male
2 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
2 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
Race (NIH/OMB)
Asian
1 Participants
n=99 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=99 Participants
Race (NIH/OMB)
White
1 Participants
n=99 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
Region of Enrollment
United States
2 Participants
n=99 Participants

PRIMARY outcome

Timeframe: After neoadjuvant therapy >4 weeks but prior to surgery

Population: Neither patient enrolled in the trial underwent resection based on post neoadjuvant therapy assessment of resectability. These patients were initially deemed potentially resectable prior to neoadjuvant therapy, but their course deviated from the initial plans. Therefore, the primary endpoint cannot be assessed.

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery

Population: Neither patient enrolled in the trial underwent resection based on post neoadjuvant therapy assessment of resectability. These patients were initially deemed potentially resectable prior to neoadjuvant therapy, but their course deviated from the initial plans. Therefore, the primary endpoint cannot be assessed.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery

Population: This outcome measure was not done. Neither patient enrolled in the trial underwent resection based on post neoadjuvant therapy assessment of resectability. These patients were initially deemed potentially resectable prior to neoadjuvant therapy, but their course deviated from the initial plans.

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)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery

Population: This outcome measure was not done. Neither patient enrolled in the trial underwent resection based on post neoadjuvant therapy assessment of resectability. These patients were initially deemed potentially resectable prior to neoadjuvant therapy, but their course deviated from the initial plans.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery

Population: This outcome measure was not done. Neither patient enrolled in the trial underwent resection based on post neoadjuvant therapy assessment of resectability. These patients were initially deemed potentially resectable prior to neoadjuvant therapy, but their course deviated from the initial plans.

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 .

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the time of esophagectomy until development of metastatic disease or death, whichever comes first

Population: This outcome measure was not done because one patient was deemed to be unsafe/unfit for surgery by the doctor. And the second patient was taken off-study prior to surgery because the principal investigator left the National Institutes of Health and closed the trial.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment start date until date of death or date last known alive.

Population: This outcome measure was not done because one patient was deemed to be unsafe/unfit for surgery by the doctor. And the second patient was taken off-study prior to surgery because the principal investigator left the National Institutes of Health and closed the trial.

Overall survival is defined as the time from treatment start date until date of death or date last known alive.

Outcome measures

Outcome data not reported

Adverse Events

Neoadjuvant Chemoradiotherapy and Esophagectomy

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Caryn Steakley

National Cancer Institute

Phone: 240-858-3749

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place