Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Wounds and Injuries

Rare Diseases

Melanoma

Sarcoma

Hyperthermia

Fever

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Melphalan

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

double isolated limb perfusion with melphalan alone

Hyperthermic isolated limb perfusion with melphalan alone is administered as a double perfusion schedule.

These two isolates limb perfusions with melphalan are treated 3-6 weeks apart. After perfusion is established, the leak rate has been determined to be acceptable, and tissue temperatures are 38 degrees Celsius, then the melphalan is administered by slow injection into an arterial line over approximately 5 minutes. The perfusion with melphalan will then continue for 60 minutes, after which the extremity is flushed out with a total of 3 liters of fluid consisting initially of a saline solution. The dose of melphalan for the second perfusion will be increased.

An attempt to resect the residual lesion between 6-12 weeks after the second

interval perfusion may be made.

Patients with extremity melanoma (Stage IIIA, IIIAB or Stage IV disease who have bulky symptomatic tumor located in the extremity) or patients with unresectable extremity sarcoma will undergo a double isolated limb perfusion with melphalan alone separated by approximately 4 to 6 weeks. The initial perfusion will be done with a melphalan dose of 6 mg/L limb volume and the interval perfusion with a dose of 9 mg/L limb volume. For patients with extremity sarcoma the tumor will be excised if feasible using a limb sparing resection between 6-12 weeks after the second perfusion. Technical feasibility of the double perfusion schedule will be determined. Overall response, duration of response, patterns of recurrence, and survival will be followed.

Pilot Study of a Double Isolation Perfusion Schedule Using Melphalan Alone for Intransit Melanoma or Unresectable Sarcoma of the Extremity

National Cancer Institute (NCI)

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Esophageal Neoplasms

Breast Neoplasms

Adenocarcinoma

Pancreatic Neoplasms

Stomach Neoplasms

Neoplasm Metastasis

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Liver Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Stomach Diseases

Pancreatic Diseases

Esophageal Cancer

Pancreatic Cancer

Ovarian Cancer

Stomach Cancer

Ovarian Epithelial Cancer

Hematinics

Gastrointestinal Agents

Liver Extracts

Pancrelipase

Pancreatin

TKM-080301

Protein Kinase Inhibitors

Enzyme Inhibitors

Udo Rudloff, M.D.

Background:

Cancer in the liver can start in the liver (e.g., primary liver cancer or hepatocellular cancer) or spread to the liver from cancers in other parts of the body (e.g. colon, pancreas, gastric, breast, ovarian, esophageal cancers, cancer with metastases to the liver.) People who have tumors that can be removed by surgery live longer than those whose cancer cannot be removed. Chemotherapy can shrink some tumors in the liver, which also helps people to live longer, and sometimes chemotherapy can shrink tumors enough that they can be removed by surgery. However, most chemotherapy drugs do not work well on tumors in the liver. In this study we are testing a new drug, TKM-080301, given directly into the cancer blood supply in the liver circulation, to see if it will cause tumors to shrink.

Objectives:

- To test the safety and effectiveness of TKM-080301 for cancer in the liver that has not responded to standard treatments.

Eligibility:

- Individuals at least 18 years of age who have inoperable cancer that has started in or spread to the liver.

Design:

* Participants will be screened with a medical history and physical exam. They will also have blood tests, and imaging studies.
* Participants will have a liver angiogram (type of X-ray study) to look at the blood flow in the liver and to place a catheter for delivery of the TKM080301.
* Participants will have a single dose of TKM-080301 given directly into the liver. After the drug has been given, the catheter will be removed. They will have frequent blood tests and keep a diary to record side effects.
* Participants may have two more doses, each dose given 2 weeks apart. {Before each dose, participants will have another angiogram and catheter placement.}They may also have liver biopsies to study the tumors.
* Two weeks after the third treatment (one full course), participants will have a physical exam, blood tests, and imaging studies. If the tumor is shrinking, they may have up to three more courses of the study drug.
* Participants will have follow up visits every 3 months for 2 years after the last course and then every 6 months as required.

BACKGROUND:

- Metastatic liver disease is a life-limiting factor for patients with a variety of cancers. For

unresectable liver metastases, the 5-year survival is \< 5%.

* For selected histologies the 5-year survival of resectable hepatic metastases ranges from 20-60%, suggesting that control of liver metastases could result in prolonged survival.
* Phase I through III trials have shown that Hepatic Arterial Infusion (HAI) is safe. However, agents used thus far in HAI have limited efficacy.
* TKM-080301 is a lipid nanoparticle (LNP) formulation containing siRNA against the PLK1 (polo-like kinase-1) gene product. More specifically, TKM-080301 is a type of LNP formulation, referred to as SNALP (Stable Nucleic Acid Lipid Particles). PLK1 has been validated as a molecular target and a prognostic factor in a variety of cancers. Inhibition of PLK1 activity in proliferating cancer cells rapidly induces mitotic arrest and apoptosis.
* This study will offer HAI with TKM-080301 to patients with unresectable and/or life threatening primary liver cancer or liver metastases.

OBJECTIVES:

Primary Objective:

- To evaluate feasibility of administering TKM-080301 via HAI and to characterize the pharmacokinetics (PK) and pharmacodynamics of TKM-080301 administered by HAI.

Secondary Objectives:

* To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of TKM-080301.
* To evaluate response rate using RECIST, PET and EASL criteria.
* To evaluate the conversion rate from unresectable to resectable disease.

ELIGIBILITY:

* Patients with unresectable colorectal, pancreas, gastric, breast, ovarian and esophageal cancers with hepatic metastases; or primary liver cancer patients who have demonstrated progressive disease following standard of care treatment.
* 18 years old or greater with an ECOG 0-2
* Laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to surgery or chemotherapy.

DESIGN:

- This is a dose escalation phase-I study testing HAI of TKM-080301 for patients with

unresectable colorectal, pancreas, gastric, breast, ovarian and esophageal cancers with hepatic metastases, or primary liver cancers.

* Up to 54 patients who meet eligibility criteria will receive HAI with TKM-080301.
* Initial dose will be 4 mg/m(2); treatment will be given every 2 weeks for up to 12 doses.
* Patients will be evaluated every 6 weeks. Patients whose tumors become resectable will be offered this option; patients who show progressive disease will be taken off treatment. All patients will be followed for survival.

TKM 080301 for Primary or Secondary Liver Cancer

A Phase 1 Dose Escalation Study of Hepatic Intra-Arterial Administration of TKM 080301 (Lipid Nanoparticles Containing siRNA Against the PLK1 Gene Product) in Patients With Colorectal, Pancreas, Gastric, Breast, Ovarian and Esophageal Cancers With Hepatic

Gemcitabine

Antimetabolites

Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.

Background:

- Pancreatic cancer is difficult to treat because by the time most cases are diagnosed, the tumors are too large to be removed surgically. Standard intravenous chemotherapy may shrink some of the tumor, but even with chemotherapy only about 25 percent of patients will live for 1 year following diagnosis. Several preliminary studies have shown that it is safe to give chemotherapy directly into the pancreas in the area of the tumor, and that giving gemcitabine over a longer period increases the amount of drug that is available to the tumor. Researchers are interested in studying whether giving the approved pancreatic cancer chemotherapy drug gemcitabine directly into the pancreas in the area of the cancer and at a slow rate of infusion is a safe and effective treatment.

Objectives:

- To test the safety and effectiveness of administering gemcitabine directly to a pancreatic tumor at a slow rate of infusion.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with pancreatic cancer that is currently too large to be removed surgically but has not yet spread to other organs.

Design:

* Participants will be screened with a full medical history and physical examination, blood and urine tests, and imaging studies.
* Participants will undergo pancreatic angiography and embolization, during which a catheter will be threaded into the blood vessels near the pancreas and a contrast dye will be used to show the blood vessels supplying the tumor. These blood vessels will then be surgically closed off.
* After the embolization, gemcitabine will be given as an infusion into the area around the tumor over 24 hours.
* Participants will return to the clinical center every 2 weeks after the first infusion for additional infusions of gemcitabine, using the same procedures as above. Participants will be monitored with frequent blood tests and imaging studies.
* Two weeks after the fourth treatment (course 1), participants will have more imaging studies, a physical examination, and blood tests. If the tumor is shrinking, participants will have two more courses of treatment (eight more infusions of gemcitabine).
* Participants will have followup visits every 3 months for 2 years following the last treatment and then every 6 months.

Background:

* Pancreatic cancer is the fourth leading cause of cancer death in the United States.
* Surgery offers the only chance at cure; however, less than 20% of patients are considered resectable at initial presentation.
* A common reason for being classified as unresectable is loco-regional advanced disease.
* Several phase I studies of regional administration of chemotherapy have proven safe.
* The main advantage of pancreatic cancer targeted arterial perfusion of Gemcitabine is achievement of higher local bio-available active drug levels at the tumor bed.
* The Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) trial is a phase I trial offering highly selective 24-hour intra-arterial administration of Gemcitabine via a subcutaneous port for patients with unresectable locally-advanced pancreatic cancer.

Objectives:

Primary Objective:

* To evaluate feasibility and toxicity of intra-arterial gemcitabine therapy (dose limiting toxicity (DLT)).
* To establish the maximum tolerated dose (MTD)

Secondary Objectives:

* To evaluate response rate using Response Evaluation Criteria in Solid Tumors (RECIST), positron emission tomography (PET), magnetic resonance imaging (MRI) and computed tomography (CT) perfusion criteria (European Association for the Study of the Liver (EASL))
* To determine progression free and overall survival.
* To evaluate the conversion rate from unresectable or borderline resectable to potentially resectable pancreatic cancer.
* To determine progression-free and overall survival.
* To analyze potential selection criteria to be used in future studies for patients who present with marginally unresectable or unresectable locally-advanced pancreatic cancer that might benefit from this approach.

Eligibility:

* Unresectable locally-advanced pancreatic cancer.
* 18 years old or greater with an Eastern Cooperative Oncology Group (ECOG) 0-2
* Laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to surgery or chemotherapy.
* No extra-pancreatic disease except regional lymph nodes.

Design:

* This is a dose escalation phase-I study.
* Patients considered unresectable due to locally-advanced pancreatic cancer will receive selective arterial perfusion of gemcitabine over 24 hours via a subcutaneous indwelling port.
* Treatment will be given on Days 1 and 14. One cycle = 4 weeks for up to six cycles.
* Three to six patients will be enrolled per dose cohort.
* 18 to 36 patients in 7 cohorts will be accrued plus 6 more patients at the maximum tolerated dose (MTD over 36 months. Patients will be evaluated every 2 cycles (8 weeks). Upon progression patients will be taken off study. If no progressive disease (PD), patients will continue up to 6 cycles.
* Chemotherapy na(SqrRoot) ve patients and patients who received previously chemotherapy including gemcitabine will be allowed, as this mode of administration has better bioavailability, offer potential for better biological effect and less systemic toxicity profiles.

Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

Here is the number of participants with DLT. DLT is defined as follows: All grade 3 or greater toxicities with the exception of Grade 3 constitutional symptoms that persist for less than 72 hours, Grade 3 and 4 myelosuppression (neutrophils and thrombocytopenia) of less than 5 days duration. Grade 3 metabolic/laboratory events that are correctable within 24 hours. Events that are assessed by the principal investigator as clearly unrelated to the agent will not be considered DLTs (e.g., events directly related to catheter insertion, pain related to underlying disease).

The MTD is the highest dose that induces dose limiting toxicity (DLT) in no more than 2 patients among a cohort of 6 patients. If 1 or fewer patients experience dose limiting toxicity than the dose level will define the MTD. Only DLT's that occurred during cycle 1 of each dose level were used to determine the MTD.

Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Progression is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum diameters while on study.

Time to progression is the time between the first day of treatment to the day of disease progression. Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.

Overall survival is defined as the time between the first day of treatment to the day of death.

Resectability is defined by the MD Anderson Resectability criteria: Resectable is no extension; normal fat plane between the tumor and the artery (superior mesenteric artery (SMA)). No extension (celiac axis/hepatic artery). Patent (superior mesenteric vein/portal vein (SMV/PV)). Borderline resectable is tumor abutment ≤180◦ (one half or less) of the circumference of the artery; periarterial stranding and tumor points of contact forming a convexity against the vessel improve chances of resection (SMA). Short-segment encasement/abutment of the common hepatic artery (typically at the gastroduodenal origin) (celiac axis/hepatic artery). Short-segment occlusion with suitable vessel above and below (SMV/PV). Locally advanced is encased (\>180◦) (SMA). Encased and no technical option for reconstruction usually because of extension to the celiac axis/splenic/left gastric junction or the celiac origin (celiac axis/hepatic artery). Occluded and no technical option for reconstruction (SMV/PV).

Number of selection criteria that can be used for unresectable pancreatic cancer.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned

Principal Investigator

All participants that received at least one dose of gemcitabine 18 mg/m(2)/24h.

gemcitabine dose escalation

Gemcitabine: Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.

18 mg/m(2)/24h

All participants that received at least one dose of gemcitabine 36 mg/m(2)/24h.

gemcitabine dose escalation

Gemcitabine: Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.

36 mg/m(2)/24h

All participants that received at least one dose of gemcitabine 72 mg/m(2)/24h.

gemcitabine dose escalation

Gemcitabine: Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.

72 mg/m(2)/24h

All participants that received at least one dose of gemcitabine 96 mg/m(2)/24h.

gemcitabine dose escalation

Gemcitabine: Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.

96 mg/m(2)/24h.

All participants that received at least one dose of gemcitabine 115 mg/m(2)/24h.

gemcitabine dose escalation

Gemcitabine: Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.

115 mg/m(2)/24h

All participants that received at least one dose of gemcitabine 18 mg/m(2)/24h, 36 mg/m(2)/24h, 72 mg/m(2)/24h, 96 mg/m(2)/24h, and/or 115 mg/m(2)/24h.

gemcitabine dose escalation

Gemcitabine: Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.

All Participants

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Time from Diagnosis to Trial Enrollment

The reference range of CA 19-9 is \<37 units/mL.

Serum CA 19-9 Level at the Time of Enrollment

Dr. Udo Rudloff

All participants that received at least one dose of gemcitabine 72 mg/m(2)/24h

gemcitabine dose escalation

Gemcitabine: Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.

All participants that received at least one dose of gemcitabine 96 mg/m(2)/24h

gemcitabine dose escalation

Gemcitabine: Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.

96 mg/m(2)/24h

Number of Participants With Dose Limiting Toxicity (DLT )

Gemcitabine Dose Escalation

MTD (Maximum Tolerated Dose)

Complete response (CR)

Partial response (PR)

Stable disease

Progressive disease (PD)

18 mg/m(2)/24h,

Response Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Data was collected for this outcome measure but not analyzed because PET scans were inconsistently obtained. There was lack of scans pre-onstudy or while patient was on treatment. Without being able to make a pre-versus-on treatment comparison, this outcome measure was not done.

Response Rate Using Positron Emission Tomography (PET)

This outcome measure was not done. No MRI data were collected. All patients had contrast-enhanced computed tomography (CTs,) and thus were followed for consistency reasons with CT and not MRI.

Response Rate Using Magnetic Resonance Imaging (MRI)

Stable disease (SD)

Response Using Computed Tomography (CT) Perfusion Criteria European Association for the Study of the Liver (EASL1)

Median Time to Progression

Median Overall Survival (OS)

Number of Participants Who Converted From Unresectable or Borderline Resectable To Potentially Resectable Pancreatic Cancer

Data was not collected and this outcome measure was not done due to an insufficient number of participants enrolled in this study.

Number of Potential Selection Criteria to Be Used in Future Studies for Patients With Marginally Unresectable Or Unresectable Locally-Advanced Pancreatic Cancer

Number of Participants With Serious and Non-Serious Adverse Events

115 mg/m(2)/24h.

Cohort 1: 5/11/11-11/9/11

Cohort 2: 6/9/11-9/17/12

Cohort 3: 12/1/11-10/6/12

Cohort 4: 12/30/11-2/17/17

Cohort 5: 3/8/12-3/9/12

Liver Diseases

Immunomodulating Agents

Three infusions of gene-modified T cells over the course of 6 weeks into the hepatic artery via a percutaneous approach.

anti-CEA 2nd generation designer T cells

Steven C Katz, MD

The purpose of this study is to collect data on the safety and potential effectiveness of 2nd generation designer T cells delivered into the hepatic circulation in patients with liver metastases expressing the CEA tumor marker. Designer T cells are prepared by collecting white blood cells from the participant, and then modifying these cells in the laboratory so that they recognize the tumor antigen, CEA. These modified cells are then given back into the participant so that they can attack and kill tumor cells. The investigators hypothesize that regional delivery of the designer T cells directly into the hepatic artery will minimize systemic toxicity and optimize the changes for therapeutic effect.

T cells have the power to destroy malignant cells under certain conditions, as demonstrated by the rare spontaneous remissions of cancer. However, the endogenous T cell response to cancer fails in the vast majority of patients and the tolerogenic conditions within the liver may pose additional immunologic barriers for those with intrahepatic metastases. The investigators modify patient T cells to kill malignant cells based on their expression of tumor antigens using antibody-defined recognition. The investigators will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors to yield "designer T cells" from normal patient cells. Prior studies in model systems demonstrated that recombinant IgCD28TCR could direct modified T cells to respond to antigen targets with IL2 secretion, cellular proliferation, and cytotoxicity - the hallmarks of an effective, self-sustaining immune response.

The present trial will test the regional infusion of anti-CEA designer T cells, given via the hepatic artery using a percutaneous approach. This is an intra-patient dose escalation trial, where patients will receive three doses over the course of six weeks. Doses are 10\^8, 10\^9 and 10\^10 modified T cells. Patients are monitored for safety and response. Patients are on-study for one month after dosing.

CEA-Expressing Liver Metastases Safety Study of Intrahepatic Infusions of Anti-CEA Designer T Cells

Phase I Trial Of Intrahepatic Infusion Of 2nd Generation Designer T Cells For Cea-Expressing Liver Metastases

CT or MRI and PET imaging will be obtained before the first infusion and following the final infusion to document changes in liver tumor size and metabolic activity.

Using liver tumor biopsy specimens and blood collection, we will determine the extent to which infused T cells enter the liver tumors in addition to circulation in the extrahepatic space.

Using tissue obtained from biopsies in addition to blood samples, the duration of T cell persistence will be assessed, in addition to cell surface markers.

Roger Williams Medical Center

Micronutrients

Vitamins

Leucovorin

Floxuridine

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

Patients with unresectable metastatic colorectal cancer confined to the liver will undergo a 1 hour hyperthermic isolated hepatic perfusion (IHP) with escalating dose melphalan. Postoperatively, patients will be treated with hepatic arterial infusion of floxuridine (FUDR), 0.2 mg/kg/day and leucovorin (LV), 15 mg/M2/day as a 2-week continuous infusion regimen. Hepatic and systemic toxicity, response to treatment, duration of response, and survival will be followed.

Patients with unresectable metastatic colorectal cancer confined to the liver will undergo a 1 hour hyperthermic isolated hepatic perfusion (IHP) with escalating dose melphalan. Postoperatively, patients will be treated with hepatic arterial infusion of floxuridine (FUDR), 0.2 mg/kg/day and leucovorin (LV), 15 mg/M(2)/day as a 2-week continuous infusion regimen. Hepatic and systemic toxicity, response to treatment, duration of response, and survival will be followed.

A Phase I Study of Isolated Hepatic Perfusion With Escalating Dose Melphalan Followed by Postoperative Hepatic Arterial Floxuridine and Leucovorin for Metastatic Unresectable Colorectal Cancers of the Liver

Isolated hepatic portal and arterial perfusion

Patients with unresectable primary or metastatic cancer confined to the liver will undergo a 1 hour hyperthermic isolated hepatic perfusion (IHP) via the portal vein and hepatic artery with escalating dose melphalan. Patients eligible for this protocol are those with non-colorectal histologies and those with colorectal cancer previously treated with intra-arterial FUDR. Hepatic and systemic toxicity, response to treatment, duration of response, and survival will be followed.

A Phase I Study of Isolated Hepatic Portal and Arterial Perfusion (IHP) With Escalating Dose Melphalan for Primary or Metastatic Unresectable Cancers of the Liver

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pilot Study of a Double Isolation Perfusion Schedule Using Melphalan Alone for Intransit Melanoma or Unresectable Sarcoma of the Extremity	NCT00001577	Melanoma Sarcoma	double isolated...	-	National Institutes of Health Clinical Center (CC)
TKM 080301 for Primary or Secondary Liver Cancer	NCT01437007	Colorectal Canc... Pancreas Cancer... Gastric Cancer ... Breast Cancer W... Ovarian Cancer ...	TKM-080301	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial	NCT01294358	Histologically ... Unresectable or...	Gemcitabine	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
CEA-Expressing Liver Metastases Safety Study of Intrahepatic Infusions of Anti-CEA Designer T Cells	NCT01373047	Liver Metastase...	anti-CEA 2nd ge...	18 Years -	Roger Williams Medical Center
A Phase I Study of Isolated Hepatic Perfusion With Escalating Dose Melphalan Followed by Postoperative Hepatic Arterial Floxuridine and Leucovorin for Metastatic Unresectable Colorectal Cancers of the Liver	NCT00001576	Colorectal Neop... Liver Neoplasm Neoplasm Metast...	Melphalan Floxuridine Leucovorin	-	National Institutes of Health Clinical Center (CC)
A Phase I Study of Isolated Hepatic Portal and Arterial Perfusion (IHP) With Escalating Dose Melphalan for Primary or Metastatic Unresectable Cancers of the Liver	NCT00001587	Liver Neoplasms Neoplasm Metast...	Isolated hepati... Melphalan	-	National Institutes of Health Clinical Center (CC)

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