Clinical trial NCT05182112: Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer with Homologous Recombination Deficiency That Has Spread to the Liver
Official title: Phase I Study of Precision CRT for Liver-Dominant Metastatic Pancreatic Cancer with Homologous Recombination Deficiency (PreCISeRT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: Metastatic Pancreatic Cancer
Homologous Recombination Deficiency
Radiation Therapy (RT)
21-443
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2022-01-10
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a phase I rolling 6 design dose escalation study.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: determine the maximum tolerated dose of focal simultaneously integrated boost (SIB)
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (All Protocol Activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (All Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (All protocol activities)
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Nassau (All Protocol Activities)
state: New York
city: West Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (All Protocol Activities)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Marsha Reyngold, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: