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PDS01ADC in Combination With Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects With Metastatic Colorectal Cancer, Intrahepatic Cholangiocarcinoma, or Metastatic Adrenocortical Carcinoma

ConditionsMetastatic Colorectal Cancer (Mcrc)Intrahepatic Cholangiocarcinoma (Icc)Intrahepatic Bile Duct CancerColorectal NeoplasmsColorectal CancerCholangiocarcinomaBile Duct NeoplasmsBile Duct CancerAdrenocortical Carcinoma (ACC)Adrenal Cortical CarcinomaAdrenal Gland CancerAdrenal Gland NeoplasmsAdrenal Cortex Neoplasms
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-120
SponsorNational Cancer Institute (NCI)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Metastatic colorectal cancer (mCRC)

Intrahepatic cholangiocarcinoma (ICC)

Adrenocortical carcinoma (ACC) with liver dominant disease

mCRC: FOLFOX or FOLFIRI

Disqualifiers

Participants who have previously received rIL-12.

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Dexamethasone

    Drug

    HAIP FUDR and Dexamethasone treatment on D1 of every cycle. Dexamethasone: (1 mg/day X pump volume / pump flow rate)

  • PDS01ADC

    Drug

    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 Hepatic Artery Infusion Pump (HAIP)

    Device

    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.

  • Floxuridine

    Drug

    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)

Treatment groups

70 Participants
are divided into 3 treatment groups
Group A: 1/ HAIP +PDS01ADC+FOLFOX or FOLFORIExperimental treatment 4 interventions
Group B: 2/ HAIP +PDS01ADC+GemOx or FOLFOXExperimental treatment 4 interventions
Group C: 3/ HAIP +PDS01ADC+GemOxExperimental treatment 4 interventions

Trial outcomes

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.

Time frame
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

1

Determine overall survival (OS)

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.

Time frame
date of enrollment until death from any cause, or after 5 years off treatment
2

Determine extra-hepatic progression-free survival (PFS)

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.

Time frame
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
3

Evaluate safety of PDS01ADC in combination with HAIP therapy

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.

Time frame
on-going from treatment start through end of treatment visit
4

Determine hepatic progression-free survival (PFS)

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.

Time frame
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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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