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

NCT05182112 | Completed Phase 1 FDA Drug

• 1 other identifier: 21-443
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 7

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.

Conditions

Pancreatic Cancer

Keywords

Metastatic Pancreatic Cancer; Homologous Recombination Deficiency; Radiation Therapy (RT); 21-443

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Radiation Therapy (RT) and Chemotherapy

EXPERIMENTAL

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 irradiation (WLI).

Radiation: Whole liver irradiation (WLI); Drug: Gemcitabine and Cisplatin

Interventions

Whole liver irradiation (WLI) RADIATION

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 assignment will be according to the dose escalation scheme, with all patients in dose level 1 receiving boost of 3600cGy to select lesions and those in dose level 2 receiving boosts of 4800cGy to select lesions. At least one lesion will be selected for dose escalation.

Radiation Therapy (RT) and Chemotherapy

Gemcitabine and Cisplatin DRUG

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 weeks will be continued until progression or unacceptable toxicity.

Radiation Therapy (RT) and Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

East White Plains, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All protocol activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (All Protocol Activities)

Rockville Centre, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Marsha Reyngold, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase I rolling 6 design dose escalation study.

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: January 10, 2022
• Study Start: December 20, 2021
• Primary Completion: November 4, 2024
• Study Completion: November 4, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

US (7)