Pancreatic CancerPhase 1NCT05182112
Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer with Homologous Recombination Deficiency That Has Spread to the Liver
A Phase 1 study testing Whole liver irradiation (WLI) and Gemcitabine and Cisplatin in people with Pancreatic Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Whole liver irradiation (WLI) and Gemcitabine and Cisplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 7 sitesUnited States
- Study dates
- 20 Dec 2021to 4 Nov 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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:
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- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
Basking Ridge, New Jersey, 07920
Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)
Commack, New York, 11725
Memorial Sloan Kettering Westchester (All Protocol Activities)
East White Plains, New York, 10604
Memorial Sloan Kettering Monmouth (All Protocol Activities)
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen (All Protocol Activities)
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center (All protocol activities)
New York, New York, 10065
Memorial Sloan Kettering Nassau (All Protocol Activities)
Rockville Centre, New York, 11553
About this study
Official title: Phase I Study of Precision CRT for Liver-Dominant Metastatic Pancreatic Cancer with Homologous Recombination Deficiency (PreCISeRT)
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
- Being tested
- Whole liver irradiation (WLI), Gemcitabine and Cisplatin
- Keywords
- Metastatic Pancreatic Cancer, Homologous Recombination Deficiency, Radiation Therapy (RT), 21-443
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Gemcitabine and CisplatinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Radiation: Whole liver irradiation (WLI); Drug: Gemcitabine and Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2022
- Study start20 Dec 2021
- Primary completion4 Nov 2024
- Study completion4 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a phase I rolling 6 design dose escalation study.
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marsha Reyngold, MD, PhD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05182112
- Sponsor's protocol ID
- 21-443
- Status last verified
- Nov 2024
- First submitted
- 20 Dec 2021
- Last updated
- 12 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Precision CRT for Liver-Dominant Metastatic Pancreatic Cancer with Homologous Recombination Deficiency (PreCISeRT)
- ClinicalTrials.gov ID
- NCT05182112
- Acronym / sponsor ID
- 21-443
- Conditions
- Pancreatic Cancer
- Keywords
- Metastatic Pancreatic Cancer, Homologous Recombination Deficiency, Radiation Therapy (RT), 21-443
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 20 Dec 2021 (actual)
- Primary completion
- 4 Nov 2024 (actual)
- Study completion
- 4 Nov 2024 (actual)
- First posted
- 10 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a phase I rolling 6 design dose escalation study.
| Arm | Type | Receives |
|---|---|---|
| Radiation Therapy (RT) and Chemotherapy | Experimental | Radiation: Whole liver irradiation (WLI), Drug: Gemcitabine and CisplatinUpon 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 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 | Radiation Therapy (RT) and Chemotherapy |
| Gemcitabine and CisplatinPatients 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. | Drug | Radiation Therapy (RT) and Chemotherapy |
Primary outcome
determine the maximum tolerated dose of focal simultaneously integrated boost (SIB)
Time frame: 1 year
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marsha Reyngold, MD, PhD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Whole liver irradiation (WLI) and Gemcitabine and Cisplatin in people with Pancreatic Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
determine the maximum tolerated dose of focal simultaneously integrated boost (SIB) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.