PDS01ADC in Combination With Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects With Metastatic Colorectal Cancer, Intrahepatic Cholangiocarcinoma, or Metastatic Adrenocortical Carcinoma
Phase II Study Evaluating the Efficacy of PDS01ADC in Combination With Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects With Metastatic Colorectal Cancer, Intrahepatic Cholangiocarcinoma, or Metastatic Adrenocortical Carcinoma
2 other identifiers
interventional
70
1 country
1
Brief Summary
Background: One way to treat liver cancer is to deliver chemotherapy drugs only to the liver (and not to the whole body). Researchers want to see if adding the drug PDS01ADC can improve the treatment. The drug triggers the immune system to fight cancer.\<TAB\> Objective: To see if treatment with HAIPs to deliver liver-directed FUDR and Dexamethasone chemotherapy in combination with PDS01ADC is effective for certain cancers. Eligibility: People aged 18 and older who have cancer of the bile ducts that is only in the liver, or colorectal cancer that has spread to the liver, or cancer of the adrenal glands that has spread to the liver, who are also receiving or planning to receive standard systemic chemotherapy for their disease. Design: Participants will be screened with: Medical history Physical exam Blood tests Pregnancy test (if needed) Tumor biopsy (if needed) Electrocardiogram Computed tomography (CT) scans Participants will have an abdominal operation. A catheter will be placed into an artery that feeds blood to the liver. The catheter will then be attached to the HAIP. The HAIP will lay under the skin on the left side of the abdomen. All participants will have liver-directed FUDR and Dexamethasone chemotherapy drugs or heparin with saline infused into the HAIP every 2 weeks. PDS01ADC will be injected under the skin every 4 weeks. They will receive this treatment until their cancer gets worse or they have bad side effects. Participants will also receive standard systemic chemotherapy for their disease, assigned based on diagnosis, through an IV by their medical oncologist (at NIH or by a local provider) every 2 weeks. Participants will have 2 study visits at NIH each month. They will have CT scans every 8 weeks. At visits, they will repeat some screening tests. Participants will have a follow-up visit 1 month after treatment ends. Then they will be contacted every 6 months for 5 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2022
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 12, 2022
CompletedFirst Posted
Study publicly available on registry
March 18, 2022
CompletedStudy Start
First participant enrolled
October 24, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
May 4, 2026
April 30, 2026
5.2 years
March 12, 2022
May 1, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Determine overall response rates
Simon optimal two-stage Phase II trial design will be used to determine overall response using RECIST criteria. The clinical response rate (CR+PR) will be determined and reported along with a 95% confidence interval, separately by cohort.
baseline, every 8 weeks while on treatment, and 4-8 weeks following initial documentation of objective response; an additional scan is performed at Week 12.
Secondary Outcomes (4)
Determine overall survival (OS)
date of enrollment until death from any cause, or after 5 years off treatment
Determine extra-hepatic progression-free survival (PFS)
date of operation to date of first observation of progressive disease within the liver or death, or after 5 years off treatment whichever comes first
Evaluate safety of PDS01ADC in combination with HAIP therapy
on-going from treatment start through end of treatment visit
Determine hepatic progression-free survival (PFS)
date of operation to date of first observation of progressive disease within the liver or death, or after 5 years off treatment whichever comes first
Study Arms (3)
1/ HAIP +PDS01ADC+FOLFOX or FOLFORI
EXPERIMENTALPDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with FOLFOX or FOLFIRI
2/ HAIP +PDS01ADC+GemOx or FOLFOX
EXPERIMENTALPDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx or FOLFOX
3/ HAIP +PDS01ADC+GemOx
EXPERIMENTALPDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx
Interventions
HAIP FUDR and Dexamethasone treatment on D1 of every cycle. Dexamethasone: (1 mg/day X pump volume / pump flow rate)
PDS01ADC will be administered by subcutaneous injection on Day 15 of every cycle. Cycle 1 at 12 mcg/kg; Cycle 2 reduced to 8 mcg/kg with the addition of systemic chemotherapy, to continue for further cycles. Note: any dose reduction in FUDR = 50% due to liver enzyme elevations means that the dose of PDS01ADC will be reduced to 4 mcg/kg.
Intera 3000 HAIP will be filled with mixture of Floxuridine and Dexamethasone in 25,000 units heparin/saline (Heparin + 0.9% Sodium Chloride) on Day 1; Days 1-14 of every cycle pump will perfuse drugs to liver. On Day 15 of each cycle, the pump will be emptied and filled with 30,000 units heparin/saline (Heparin + 0.9% Sodium Chloride); Days 15-28 of every cycle will perfuse heparin/saline to liver.
HAIP FUDR and Dexamethasone treatment on D1 of every cycle. Floxuridine: (0.12 mg/kg x ideal average body weight in kg X 30 mL \[pump volume\] / Pump Flow Rate)
Eligibility Criteria
You may qualify if:
- Participants must have a documented diagnosis of one of the following cancers:
- Metastatic colorectal cancer (mCRC)
- Intrahepatic cholangiocarcinoma (ICC)
- Adrenocortical carcinoma (ACC) with liver dominant disease
- Participants must have an identified medical oncologist who has recommended and is planning to oversee treatment with one of the following standard chemotherapy regimens (based on disease type) not to begin sooner than 28 days after initiation of study-directed HAIP intervention:
- mCRC: FOLFOX or FOLFIRI
- ICC: GemOx or FOLFOX
- ACC: GemOx
- Age \>= 18 years.
- Negative serum or urine pregnancy test at screening for individuals of childbearing potential (IOCBP).
- NOTE: IOCBP is defined as any individual who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. IOCBP must have a negative pregnancy test (HCG blood or urine) during screening.
- All participants (regardless of childbearing potential) must agree to use highly effective contraception prior to study entry, for the duration of study participation, and for 3 months after completion of study treatment for those able to father a child or 6 months after completion of study treatment for those of child-bearing potential (i.e., IOCBP). Highly effective birth control (failure rate of less than 1%), e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner and sexual abstinence. Note: The use of condoms by participants who are able to get other individuals pregnant is required unless the partner of childbearing potential is permanently sterile.
- Nursing (including breastfeeding) participants must agree to discontinue nursing.
- Arterial anatomy on CT angiogram or CT chest, abdomen and pelvis multiphase (i.e., CT C/A/P multiphase) amenable to placement of the HAIP.
- Participant must sign the informed consent form to participate in this study.
- +40 more criteria
You may not qualify if:
- Participants who are receiving any other investigational agents.
- Participants who have previously received rIL-12.
- Participants with active autoimmune diseases, that might deteriorate when receiving an immunostimulatory agent with the exceptions:
- diabetes type I, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible;
- participants requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses \<= 10 mg of prednisone or equivalent per day;
- administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is eligible.
- History of organ transplant, except for transplants that do not require immunosuppression.
- History of or active inflammatory bowel disease (e.g., Crohn s disease, ulcerative colitis).
- Known hypersensitivity or allergic reactions attributed to any compounds of similar chemical or biologic composition to the study medication, such as recombinant IL-12 or other monoclonal antibodies and history of allergic reactions attributed to compounds of similar chemical composition to FUDR or heparin.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke \< 6 months prior to enrollment, myocardial infarction \< 6 months prior to enrollment, unstable angina, congestive heart failure (\>= NYHA III) or serious cardiac arrhythmia requiring medication.
- All conditions associated with significant necrosis of nontumor-bearing tissues.
- Esophageal or gastroduodenal ulcers \< 6 months prior to treatment.
- Active ischemic bowel disease.
- Psychiatric illness/social situations that would limit compliance with study requirements.
- Active concurrent malignancies within the last five years other than colorectal primary except basal cell skin carcinoma and thyroid carcinoma.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (1)
Victory JH, Smith EC, Ryan CE, Lambdin J, Sarvestani AL, Friedman LR, Eade AV, Larrain C, Pu T, Luberice K, Ramamoorthy B, Rainey AJ, Hannah CE, Smith KM, Mabry D, Xie C, Davis JL, Blakely AM, Gulley JL, Schlom J, Monge C, Greten TF, Hernandez JM. Hepatic artery infusion pump (HAIP) therapy in combination with targeted delivery of IL-12 for patients with metastatic colorectal cancer or intrahepatic cholangiocarcinoma: a phase II trial protocol. J Gastrointest Oncol. 2024 Jun 30;15(3):1348-1354. doi: 10.21037/jgo-24-71. Epub 2024 Jun 20.
PMID: 38989414DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jonathan M Hernandez, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 12, 2022
First Posted
March 18, 2022
Study Start
October 24, 2022
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2028
Last Updated
May 4, 2026
Record last verified: 2026-04-30
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely.@@@@@@@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.
All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.