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Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01294358
First received: February 10, 2011
Last updated: October 15, 2014
Last verified: September 2014
  Purpose

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.

Condition Intervention Phase
Histologically or Cytologically Confirmed Pancreatic Ca
Unresectable or Borderline Resectable Pancreatic Ca
Drug: Gemcitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To evaluate feasibility and DLT (dose limiting toxicity). [ Time Frame: three years ] [ Designated as safety issue: Yes ]
  • To establish the MTD (maximal tolerated dose) [ Time Frame: three years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To Evaluate response rate using RECIST, PET, MRI and CT perfusion criteria [ Time Frame: three years ] [ Designated as safety issue: No ]
  • Determine progression-free and overall survival [ Time Frame: three years ] [ Designated as safety issue: No ]
  • To evaluate the conversion rate from unresectable or borderline resectable to [ Time Frame: three years ] [ Designated as safety issue: No ]
  • To analyze potential selection criteria to be used in future studies for patients [ Time Frame: three years ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: January 2011
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
gemcitabine dose escalation
Drug: Gemcitabine
N/A

Detailed Description:

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 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 (DLT).
  • To establish the maximum tolerated dose (MTD)

Secondary Objectives:

  • To evaluate response rate using RECIST, PET, MRI and CT perfusion criteria (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 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 MTD over 36 months. Patients will be evaluated every 2 cycles (8 weeks). Upon progression patients will be taken off study. If no 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Histologically or cytologically confirmed locally advanced pancreatic adenocarcinoma or clinical and radiographic evidence of pancreatic cancer

Note: Patients with a limited disease burden outside the pancreas, who have undergone systemic chemotherapy for metastatic disease and have achieved a complete response on the metastatic lesions of greater than or equal to 6 months, and have no evidence of disease outside the pancreas at time of enrollment, are eligible.

  • Disease must be evaluable
  • Disease should be deemed unresectable by the MD Anderson criteria
  • Patients may be chemo naive or have received prior chemotherapy (including Gemcitabine) and/or radiation
  • Greater than or equal to 18 years of age
  • Must be able to understand and sign the Informed Consent Document
  • Clinical performance status of ECOG less than or equal to 2
  • Life expectancy of greater than three months
  • Patients of both genders must be willing to practice birth control during and for four months after receiving chemotherapy
  • Hematology:

    • Absolute neutrophil count greater than 1300/mm(3) without the support of Filgrastim.
    • Platelet count greater than 75,000/mm(3).
    • Hemoglobin greater than 8.0 g/dl.
  • Chemistry:

    • Serum ALT/AST less or equal to 3 times the upper limit of normal, unless patient carries a biliary stent. For these patients, to account for asymptomatic, transient elevations in transaminases ('transaminitis'), serum ALT/AST may be less than or equal to 5 tims the upper limit of normal provided all other eligibility parameters are met.
    • Serum creatinine less than or equal to 1.8 mg/dl unless the measured creatinine clearance is greater than 60 mL/min/1.73 m(2)
    • Total bilirubin less than or equal to 2 mg/dl,
    • PT within 2 seconds of the upper limit of normal or INR less than or equal to 1.8
  • No history of prior/other malignancies within the 2 years prior to enrollment with the exception of basal cell carcinoma

EXCLUSION CRITERIA:

  • Metastatic disease including malignant ascities
  • Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
  • Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, heart failure
  • Childs B or C cirrhosis or with evidence of severe portal hypertension by history, endoscopy, or radiologic studies
  • Weight less than 40 kg
  • Significant ascites, greater than 1000cc in the absence of peritoneal disease
  • Concomitant medical problems that would place the patient at an unacceptable risk for the procedure
  • Need for concurrent chemotherapy
  • Discretion of the PI
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01294358

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Udo Rudloff, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT01294358     History of Changes
Other Study ID Numbers: 110099, 11-C-0099
Study First Received: February 10, 2011
Last Updated: October 15, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Pancreatic Cancer
Regional Therapy
Selective Arterial Infusion
Locally Advanced Disease

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014