Radiation Therapy (RT) And Chemotherapy For The Treatment Of Pancreatic Cancer With Homologous Recombination Deficiency That Has Spread To The Liver

Study Overview

Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer with Homologous Recombination Deficiency That Has Spread to the Liver

The researchers are doing this study to test the combination of radiation therapy (RT) and low dose chemotherapy in people with metastatic pancreatic cancer that has a homologous recombination deficiency (HRD) and has spread to the liver. The researchers will try to find the highest safe and effective dose of individualized dose-painted RT that can be given to the liver when combined with standard low dose chemotherapy. The conformal dose painted RT treatment plan will include higher doses of radiation to the areas of the liver where tumors can be seen, and a lower dose to the entire liver. The study will also look at blood samples from participants to learn why some people may respond to study treatment (whole liver RT in combination with low dose chemotherapy) better than others.

N/A

Pancreatic Cancer

RADIATION: Whole liver irradiation (WLI)
DRUG: Gemcitabine and Cisplatin

21-443

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-12-20	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-11-08
First Submitted that Met QC Criteria 2021-12-20	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-11-12
First Posted (ACTUAL) 2022-01-10	Results First Posted N/A	Last Verified 2024-11

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Radiation Therapy (RT) and Chemotherapy Upon enrollment in the study, patients will undergo radiation simulation. Protocol therapy will start upon completion of RT planning (1-2 weeks). Chemoradiation will be initiated 1-2 weeks later depending on RT planning and consist of whole liver irradiat	RADIATION: Whole liver irradiation (WLI) Whole liver irradiation (WLI) to a total dose 1800cGy in 10 fractions will be given over 2 weeks with simultaneously integrated boost (SIB) to deliver focal doses of 3600cGy (dose level 1) and 4800cGy (dose level 2) to select gross lesions. SIBl dose assi DRUG: Gemcitabine and Cisplatin Patients will start cisplatin 10 mg/m2 and gemcitabine 600 mg/m2 intravenously q2 weeks for 1 cycle while undergoing simulation and radiation treatment planning procedures. After completion of CRT, adjuvant cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 q2

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Radiation Therapy (RT) and Chemotherapy

Upon enrollment in the study, patients will undergo radiation simulation. Protocol therapy will start upon completion of RT planning (1-2 weeks). Chemoradiation will be initiated 1-2 weeks later depending on RT planning and consist of whole liver irradiat

RADIATION: Whole liver irradiation (WLI)

Whole liver irradiation (WLI) to a total dose 1800cGy in 10 fractions will be given over 2 weeks with simultaneously integrated boost (SIB) to deliver focal doses of 3600cGy (dose level 1) and 4800cGy (dose level 2) to select gross lesions. SIBl dose assi

DRUG: Gemcitabine and Cisplatin

Patients will start cisplatin 10 mg/m2 and gemcitabine 600 mg/m2 intravenously q2 weeks for 1 cycle while undergoing simulation and radiation treatment planning procedures. After completion of CRT, adjuvant cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 q2

Primary Outcome Measures	Measure Description	Time Frame
determine the maximum tolerated dose of focal simultaneously integrated boost (SIB)	we will use a rolling 6 dose-escalation design which allows for accrual of two to six patients concurrently onto a dose level (hence tends to shorten the study conduct timeline) based on the number of patients currently enrolled and evaluable, the number experiencing dose-limiting toxicity (DLT), and the number still at risk of developing a DLT.	1 year

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically or cytologically confirmed adenocarcinoma of the pancreas metastatic to the liver (liver metastases confirmed pathologically or radiographic liver lesions most consistent with metastases in a patient with pathologically proven pancreatic adenocarcinoma)
Germline or biallelic somatic pathogenic mutations in the core HR genes including BRCA1, BRCA2, PALB2 and ATM genes are required for dose escalating cohort. Pathogenic germline or biallelic somatic alterations in other HR genes including (BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, RTEL1) are allowed in the expansion cohort. Confirmation of the required mutations can be from MSK IMPACT or any other approved germline genetic testing for eligibility purposes.
≥1 liver lesion(s) measurable on a contrast-enhanced liver CT, MRI or PET/CT performed within 6 weeks prior to study entry. Any tumor location within the liver is allowed
At least 1 liver metastasis measuring ≤ 7 cm
Extrahepatic disease outside the liver is permitted if the hepatic disease is judged to be life-limiting (1-2 sites of disease are allowed, including lung and non-regional nodes, up to and including 5 individual lesions)
Age ≥18
ECOG 0-2
Any prior chemotherapy therapy is allowed including prior treatment with platinum containing chemotherapy and irrespective of response to prior therapy
Prior treatment with FDA-approved or investigational biologics or novel molecularly targeted therapies, including oral or IV formulations, are permitted. Patients must be off prior targeted therapy for at least 14 days or 4 half-lives prior to the initiation of the study treatment
Use of an effective means of contraception in men and women of child-bearing potential
Adequate organ and marrow function within 14 days prior to study entry, defined as:
Absolute neutrophil count (ANC)>1000/mm3
Hemoglobin >9 gm/dl (Note: The use of transfusion or other intervention to achieve Hgb > 9.0 g/dl is acceptable.)
Platelets >100,000/mm3
Serum creatinine <1.5 mg/dl OR creatinine clearance of >50 cc/min
Total bilirubin < 1.8 mg/dL
Prothrombin time/INR < 1.7
Albumin ≥ 28 g/L
AST and ALT < 3 times ULN
ALP < 2.5 times ULN

Prior invasive malignancy, except non-melanoma skin cancer, unless disease free for a minimum of 3 years
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
History of underlying liver disease, including but not limited to cirrhosis, hepatitis or hemochromatosis
History of major liver resection
Variants of unknown significance (VUS) in core or non-core HR genes will be excluded
Severe, active co-morbidity, defined as follows:

Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
Transmural myocardial infarction within the last 6 months
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
Clinical ascites.
Single right kidney. (A single left kidney is allowed)
Absolute contraindication to cisplatin including severe hypersensitivity
Pregnancy, nursing women, or women of childbearing potential, and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Marsha Reyngold, MD, PhD, Memorial Sloan Kettering Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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