Trial Outcomes & Findings for Low-Dose Radiation Therapy to the Whole Liver With Gemcitabine and Cisplatin in IHC (NCT NCT02254681)

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

16 weeks after treatment start

Results posted on

2018-10-03

Participant Flow

6 subjects recruited from 9/2014-12/2015

Participant milestones

Participant milestones
Measure	Treatment Four three-week treatment cycles. Gemcitabine (1000 gm/m\^2) and cisplatin (25 mg/m\^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle. Gemcitabine Cisplatin Low dose whole liver and portal lymph node basin radiotherapy
Overall Study STARTED	6
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Four three-week treatment cycles. Gemcitabine (1000 gm/m\^2) and cisplatin (25 mg/m\^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle. Gemcitabine Cisplatin Low dose whole liver and portal lymph node basin radiotherapy
Overall Study Lack of Efficacy	6

Baseline Characteristics

Low-Dose Radiation Therapy to the Whole Liver With Gemcitabine and Cisplatin in IHC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment n=6 Participants Four three-week treatment cycles. Gemcitabine (1000 gm/m\^2) and cisplatin (25 mg/m\^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle. Gemcitabine Cisplatin Low dose whole liver and portal lymph node basin radiotherapy
Age, Continuous	64 years STANDARD_DEVIATION 0 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 16 weeks after treatment start

Population: decision was made to close the study due to the futility of the regimen in the first 6 subjects, as well as the lack of funding to complete the study.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

Outcome measures

Outcome measures
Measure	Treatment n=6 Participants Four three-week treatment cycles. Gemcitabine (1000 gm/m\^2) and cisplatin (25 mg/m\^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle. Gemcitabine Cisplatin Low dose whole liver and portal lymph node basin radiotherapy decision was made to close the study due to the futility of the regimen in the first 6 subjects, as well as the lack of funding to complete the study.
Number of Participants With Radiographic Disease Response After Combination Low-dose Radiotherapy and Gemcitabine-cisplatin. Stable Disease	5 Participants
Number of Participants With Radiographic Disease Response After Combination Low-dose Radiotherapy and Gemcitabine-cisplatin. Partial Response	1 Participants

PRIMARY outcome

Timeframe: up to 16 weeks after treatment start

Number of participants with adverse events during combined low-dose radiotherapy and gemcitabine-cisplatin treatment.

Outcome measures

Outcome measures
Measure	Treatment n=6 Participants Four three-week treatment cycles. Gemcitabine (1000 gm/m\^2) and cisplatin (25 mg/m\^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle. Gemcitabine Cisplatin Low dose whole liver and portal lymph node basin radiotherapy decision was made to close the study due to the futility of the regimen in the first 6 subjects, as well as the lack of funding to complete the study.
Number of Participants With Adverse Events. Study related Adverse events	6 Participants
Number of Participants With Adverse Events. No study related Adverse Events	0 Participants

SECONDARY outcome

Timeframe: up to 90 days after partial hepatectomy

Population: 1 of 6 subjects had surgery therefore only 1 subject was analyzed for post-operative complications.

Measured post-operative complications include (but not limited to) bile leak, liver failure, ascites, infection, any organ failure or insufficiency, venous thromboembolism, and mortality.

Outcome measures

Outcome measures
Measure	Treatment n=1 Participants Four three-week treatment cycles. Gemcitabine (1000 gm/m\^2) and cisplatin (25 mg/m\^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle. Gemcitabine Cisplatin Low dose whole liver and portal lymph node basin radiotherapy decision was made to close the study due to the futility of the regimen in the first 6 subjects, as well as the lack of funding to complete the study.
Number of Participants With Post-operative Complications After Partial Hepatectomy After Antecedent Combination Low-dose Radiotherapy and Gemcitabine-cisplatin.	1 Participants

SECONDARY outcome

Timeframe: 16 weeks after start of first treatment

Population: data not collected

Tumor tissue will be obtained by either biopsy or liver resection after combination chemoradiotherapy. Histologic response will be determined by extent of viable tumor, tumor necrosis, and surrounding fibrosis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 16 weeks after start of first treatment.

Population: data not collected

Background (non-tumor bearing) liver tissue will be obtained by either biopsy or liver resection after combination chemoradiotherapy. Histologic markers of Radiation Induced Liver disease will be measured.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From date of partial hepatectomy until date of first documented recurrence or date of death from any cause, assessed up to 24 months.

Population: Only 1 of the 6 subjects had surgery to assess recurrence after hepatectomy.

To determine the number of participants with Intrahepatic recurrence assessed by RECIST criteria using MRI of the abdomen with intravenous gadolinium contrast.

Outcome measures

Outcome measures
Measure	Treatment n=1 Participants Four three-week treatment cycles. Gemcitabine (1000 gm/m\^2) and cisplatin (25 mg/m\^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle. Gemcitabine Cisplatin Low dose whole liver and portal lymph node basin radiotherapy decision was made to close the study due to the futility of the regimen in the first 6 subjects, as well as the lack of funding to complete the study.
Number of Participants With Intrahepatic Recurrence After Partial Hepatectomy With Antecedent Combination Low-dose Radiotherapy and Gemcitabine-cisplatin.	1 Participants

SECONDARY outcome

Timeframe: From date of first treatment until date of first documented progression or date of death from any cause, which ever comes first, assessed up to 24 months.

To determine the number of participants with Intrahepatic disease progression assessed by MRI of the abdomen with intravenous gadolinium contrast using RECIST criteria.

Outcome measures

Outcome measures
Measure	Treatment n=6 Participants Four three-week treatment cycles. Gemcitabine (1000 gm/m\^2) and cisplatin (25 mg/m\^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle. Gemcitabine Cisplatin Low dose whole liver and portal lymph node basin radiotherapy decision was made to close the study due to the futility of the regimen in the first 6 subjects, as well as the lack of funding to complete the study.
Number of Participants With Intrahepatic Disease Progression After Treatment With Combination Low-dose Radiotherapy and Gemcitabine-cisplatin.	6 Participants

Adverse Events

Treatment

Serious events: 1 serious events

Other events: 6 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Treatment n=6 participants at risk Four three-week treatment cycles. Gemcitabine (1000 gm/m\^2) and cisplatin (25 mg/m\^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle. Gemcitabine Cisplatin Low dose whole liver and portal lymph node basin radiotherapy
Hepatobiliary disorders cholelithiasis	16.7% 1/6 • Number of events 1 • 1.5 years

Other adverse events

Other adverse events
Measure	Treatment n=6 participants at risk Four three-week treatment cycles. Gemcitabine (1000 gm/m\^2) and cisplatin (25 mg/m\^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle. Gemcitabine Cisplatin Low dose whole liver and portal lymph node basin radiotherapy
Blood and lymphatic system disorders anemia	16.7% 1/6 • Number of events 1 • 1.5 years
Investigations neutropenia	66.7% 4/6 • Number of events 4 • 1.5 years
Investigations thrombocytopenia	33.3% 2/6 • Number of events 2 • 1.5 years
Metabolism and nutrition disorders hypomagnesemia	50.0% 3/6 • Number of events 5 • 1.5 years
Metabolism and nutrition disorders hyponatremia	16.7% 1/6 • Number of events 1 • 1.5 years
Gastrointestinal disorders nausea	33.3% 2/6 • Number of events 2 • 1.5 years
Gastrointestinal disorders pain	33.3% 2/6 • Number of events 2 • 1.5 years

Additional Information

Srinevas K. Reddy

Allina Health

Phone: 612-863-8716

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place