PDS01ADC in Combination With Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects With Metastatic Colorectal Cancer, Intrahepatic Cholangiocarcinoma, or Metastatic Adrenocortical Carcinoma
- Conditions
- Intrahepatic Cholangiocarcinoma (Icc)Colorectal CancerColorectal NeoplasmsCholangiocarcinomaBile Duct CancerMetastatic Colorectal Cancer (Mcrc)Intrahepatic Bile Duct CancerBile Duct Neoplasms
- Interventions
- Device: Intera 3000 Hepatic Artery Infusion Pump (HAIP)Drug: PDS01ADC
- Registration Number
- NCT05286814
- Lead Sponsor
- National Cancer Institute (NCI)
- 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 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.
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.
Participants will have 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 get systemic chemotherapy through an IV or mediport every 2 weeks. They will receive this treatment until their cancer gets worse or they have bad side effects.
Participants will have 2 study visits 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.
- Detailed Description
Background:
Regional chemotherapy for hepatic malignancies takes advantage of the fact that tumors are perfused almost exclusively by the hepatic artery and, that the agent used (Floxuridine, FUDR) has a 95% first-pass metabolism by the liver.
Early clinical trials performed during the 1970's and 1980's demonstrated impressive response rates that led to the adoption of hepatic artery infusion pump chemotherapy (HAIP) at select centers; however, little has changed in the ensuing decades with respect to regional
therapy for the liver, although there has been continued and even renewed interest.
Dose reductions of FUDR are common after several treatments, which has limited both the magnitude and duration of treatment responses in many cases.
We posit that the logical and much-needed next step in regional therapy is to take advantage of the FUDR-induced tumor necrosis with an agent able to activate local tumor immunity for a synergistic effect.
PDS01ADC is an immunocytokine composed of two IL-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA), and targets regions of tumor necrosis where DNA has become exposed. PDS01ADC targets necrotic areas of the tumor and activates immune cells in the tumor microenvironment to induce a Th1 polarization of lymphocytes and the release of IFN-gamma. IFN-gamma in turn induces a host of immunomodulatory effects that contribute to robust antitumor responses that are localized within the tumor microenvironment, with no systemic distribution or exposure to IL-12.
Data from a recent Phase I study demonstrate that subcutaneous administration of PDS01ADC is safe and a MTD has been determined. Moreover, preclinical models indicate that PDS01ADC synergizes with therapies able to effectively induce tumor necrosis, which may also
minimize toxicity by limiting off-target exposure.
Objective:
-To determine the objective response rate (ORR) in participants with unresectable metastatic colorectal cancer (mCRC), intrahepatic cholangiocarcinoma (ICC), or adrenocortical carcinoma (ACC) with liver dominant disease treated with PDS01ADC in combination with HAIP and systemic therapy.
Eligibility:
* Histologically or cytologically confirmed, unresectable, colorectal adenocarcinoma metastatic to the liver (Cohort 1), intrahepatic cholangiocarcinoma (Cohort 2) or adrenocortical carcinoma with liver dominant disease (Cohort 3)
* No evidence of extrahepatic metastases
* Participants must have received first-line systemic chemotherapy.
* Age \>= 18 years
Design:
-Open label, single center, non-randomized Phase II study
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 48
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1/ HAIP +PDS01ADC+FOLFOX or FOLFORI Floxuridine PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with FOLFOX or FOLFIRI 1/ HAIP +PDS01ADC+FOLFOX or FOLFORI 5-Fluorouracil PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with FOLFOX or FOLFIRI 1/ HAIP +PDS01ADC+FOLFOX or FOLFORI Irinotecan PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with FOLFOX or FOLFIRI 1/ HAIP +PDS01ADC+FOLFOX or FOLFORI Intera 3000 Hepatic Artery Infusion Pump (HAIP) PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with FOLFOX or FOLFIRI 1/ HAIP +PDS01ADC+FOLFOX or FOLFORI Oxaliplatin PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with FOLFOX or FOLFIRI 1/ HAIP +PDS01ADC+FOLFOX or FOLFORI Leucovorin PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with FOLFOX or FOLFIRI 1/ HAIP +PDS01ADC+FOLFOX or FOLFORI PDS01ADC PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with FOLFOX or FOLFIRI 1/ HAIP +PDS01ADC+FOLFOX or FOLFORI Dexamethasone PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with FOLFOX or FOLFIRI 2/HAIP +PDS01ADC+GemOx Floxuridine PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx 2/HAIP +PDS01ADC+GemOx 5-Fluorouracil PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx 2/HAIP +PDS01ADC+GemOx Irinotecan PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx 2/HAIP +PDS01ADC+GemOx Intera 3000 Hepatic Artery Infusion Pump (HAIP) PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx 2/HAIP +PDS01ADC+GemOx Oxaliplatin PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx 2/HAIP +PDS01ADC+GemOx Leucovorin PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx 2/HAIP +PDS01ADC+GemOx PDS01ADC PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx 2/HAIP +PDS01ADC+GemOx Gemcitabine PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx 2/HAIP +PDS01ADC+GemOx Dexamethasone PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx
- Primary Outcome Measures
Name Time Method Determine overall response rates baseline, every 8 weeks while on treatment, and 4-8 wkks following initial documentation of objective response 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.
- Secondary Outcome Measures
Name Time Method Determine overall survival (OS) date of enrollment until death from any cause, or after 5 years off treatment CT will be used for response criteria. Overall survival (OS) probability will be determined using Kaplan-Meier estimates for all participants, separately by cohort; the median OS will be reported along with a 95% confidence interval.
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 CT will be used for response criteria. Extra-hepatic progression-free survival (PFS) probability will be determined using Kaplan-Meier estimates for all participants, separately by cohort; the median PFS will be reported along with a 95% confidence interval.
Evaluate safety of PDS01ADC in combination with HAIP therapy on-going from treatment start through end of treatment visit Safety will be assessed by analyzing the type, grade and frequency. Toxicities by grade and per participant will be determined and reported separately by disease cohort.
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 CT will be used for response criteria. Hepatic progression-free survival (PFS) probability will be determined using Kaplan-Meier estimates for all participants, separately by cohort; the median PFS will be reported along with a 95% confidence interval.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States