NCT03069950

Brief Summary

The purpose of this study is to see if patients treated with both regional chemotherapy using the HAI pump and intravenous chemotherapy are able to have their liver tumors removed surgically (resected), versus treatment with only intravenous chemotherapy.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Feb 2017

Geographic Reach
1 country

5 active sites

Status
withdrawn

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

February 28, 2017

Completed
Same day until next milestone

Study Start

First participant enrolled

February 28, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 3, 2017

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 16, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 16, 2019

Completed
Last Updated

May 21, 2019

Status Verified

May 1, 2019

Enrollment Period

2.2 years

First QC Date

February 28, 2017

Last Update Submit

May 17, 2019

Conditions

Keywords

Hepatic Arterial InfusionFloxuridine (FUDR)Irinotecan (CPT-11)FLUOROURACILPANITUMUMAB16-1341

Outcome Measures

Primary Outcomes (1)

  • Resection rate assessed using RECIST (version 1.1)

    Treatment evaluation will be done using RECIST (version 1.1) The patient will be assessed with repeat CT scans as specified. If at any time after 3 cycles (or 3 months) the patient is able to undergo a complete resection of all hepatic metastases they will proceed to operative assessment.

    3 months

Study Arms (2)

HAI FUDR/Dex in addition to Pmab plus FOLFIRI

EXPERIMENTAL

Panitumumab plus FOLFIRI on Day 1 and Day 15 of each cycle. HAI pump therapy with FUDR and Dex on Day 1 of each cycle. Patients will start protocol therapy approximately 2 weeks after surgery. All patients will receive Panitumumab (6 mg/kg IV over 60 min). The HAI FUDR group will receive FOLFIRI in the following dosing; 5-Fluouracil (5FU) (1000 mg/m2/day continuous infusion over two days), Leucovorin (LV) (400 mg/m2 IV over 30 min to an hour), and Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and Day 15.

Drug: Floxuridine (FUDR)Drug: Irinotecan (CPT-11)Drug: FLUOROURACILDrug: PANITUMUMABDrug: DEXAMETHASONEDrug: Leucovorin

Pmab plus FOLFIRI alone

EXPERIMENTAL

The dosing of FOLFIRI in the systemic arm will be 5-Fluouracil (5FU) (1200 mg/m2/day continuous infusion over two days), Leucovorin (LV) (400 mg/m2 IV over 30 min to an hour), bolus 5FU 400mg/ m2 and Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and 15.

Drug: Floxuridine (FUDR)Drug: Irinotecan (CPT-11)Drug: FLUOROURACILDrug: PANITUMUMABDrug: Leucovorin

Interventions

5-Fluouracil (5FU) (1000 mg/m2/day continuous infusion over two days)

HAI FUDR/Dex in addition to Pmab plus FOLFIRIPmab plus FOLFIRI alone

Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and Day 15.

HAI FUDR/Dex in addition to Pmab plus FOLFIRIPmab plus FOLFIRI alone

5-Fluouracil (5FU) (1200 mg/m2/day continuous infusion over two days)

HAI FUDR/Dex in addition to Pmab plus FOLFIRIPmab plus FOLFIRI alone

Panitumumab (6 mg/kg IV over 60 min)

HAI FUDR/Dex in addition to Pmab plus FOLFIRIPmab plus FOLFIRI alone

flat dose of 25 mg on Day 1

HAI FUDR/Dex in addition to Pmab plus FOLFIRI

Leucovorin (LV) (400 mg/m2 IV over 30 min to an hour)

HAI FUDR/Dex in addition to Pmab plus FOLFIRIPmab plus FOLFIRI alone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • History of histologically confirmed colorectal adenocarcinoma metastatic to the liver with no clinical or radiographic evidence of extrahepatic disease. Confirmation of diagnosis must be performed by the enrolling institution.
  • Patients must have a primary L sided colorectal cancer, (at or distal to the splenic flexure)
  • Confirmed RAS/RAF wild type tumor. Paraffin-embedded tumor tissue obtained from the primary tumor or metastasis
  • Have received prior treatment for metastatic disease with oxaliplatin-based regimen and either
  • Had disease progression OR
  • Had stable disease OR
  • Discontinued oxaliplatin due to neuropathy
  • Patients must meet the following criteria for unresectability as determined by two hepatobiliary surgeons and one radiologist:
  • When a margin negative resection would require resection of all three hepatic veins, both portal veins, or the retrohepatic vena cava.
  • Requiring a resection that leaves less than 2 hepatic segments (not including the caudate lobe) behind with adequate arterial/portal inflow, venous outflow and biliary drainage. \*\*
  • \*\*A patient is considered resectable if the procedure includes a minor wedge or thermo-ablation encompassing 10% or less of the volume of the remaining 2 segments.
  • Patient"s liver metastases must comprise \<70% of the liver parenchyma. All patients must be clinically fit to undergo surgery as determined by the pre-operative evaluation
  • Lab values within 14 days prior to enrollment/randomization:
  • WBC ≥ 3.0 K/uL
  • ANC \> 1.5 K/uL
  • +9 more criteria

You may not qualify if:

  • Patients \< 18 years of age
  • Patients who have received more than one chemotherapy regimen for metastatic disease
  • Patients who are chemotherapy naïve
  • Prior radiation to the liver (Prior radiation therapy to the pelvis is acceptable if completed at least 4 weeks prior to registration)
  • Active infection
  • °Active infection includes patients with positive blood cultures
  • Prior treatment with HAI FUDR
  • Prior TACE
  • Female patients who are pregnant or lactating - or planning to become pregnant within 6 months after the end of the treatment (female patients of child-bearing potential must have negative pregnancy test ≤ 72 hours before enrollment and randomization, and must have a negative pregnancy test ≤ 72 hours prior to treatment start)
  • If a patient has any serious medical problems which may preclude receiving this type of treatment
  • Patients with history or known presence of primary CNS tumors, seizures not well-controlled with standard medical therapy, or history of stroke will also be excluded.
  • Serious or non-healing active wound, ulcer, or bone fracture
  • History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
  • Patients who have a diagnosis of Gilbert"s disease
  • History of other malignancy, except:
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memoral Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

MeSH Terms

Interventions

FloxuridineIrinotecanFluorouracilPanitumumabDexamethasoneLeucovorin

Intervention Hierarchy (Ancestors)

DeoxyuridineUridinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesCamptothecinAlkaloidsUracilPyrimidinonesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, FluorinatedFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCoenzymesEnzymes and Coenzymes

Study Officials

  • Andrea Cercek, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 28, 2017

First Posted

March 3, 2017

Study Start

February 28, 2017

Primary Completion

May 16, 2019

Study Completion

May 16, 2019

Last Updated

May 21, 2019

Record last verified: 2019-05

Locations