Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

NCT01294358 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: 11009911-C-0099P10764
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Histologically or Cytologically Confirmed Pancreatic Ca; Unresectable or Borderline Resectable Pancreatic Ca

Keywords

Pancreatic Cancer; Regional Therapy; Selective Arterial Infusion; Locally Advanced Disease

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicity (DLT )

  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).

  Cycle 1 (4 weeks), for up to 6 cycles

• MTD (Maximum Tolerated Dose)

  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.

  Cycle 1 (4 weeks), for up to 6 cycles

Secondary Outcomes (9)

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

  Every 2 cycles (8 weeks), up to 18 weeks

• Response Rate Using Positron Emission Tomography (PET)

  Every 2 cycles (8 weeks), up to 18 weeks

• Response Rate Using Magnetic Resonance Imaging (MRI)

  Every 2 cycles (8 weeks), up to 18 weeks

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

  Every 2 cycles (8 weeks), up to 18 weeks

• Median Time to Progression

  From first day of treatment to the day of progression, assessed up to 221 months

Study Arms (1)

Gemcitabine Dose Escalation

EXPERIMENTAL

gemcitabine dose escalation

Drug: Gemcitabine

Interventions

Gemcitabine DRUG

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.

Also known as: Gemzar

Gemcitabine Dose Escalation

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Eastern Cooperative Oncology Group (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:

You may not qualify if:

• Metastatic disease including malignant ascites
• 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 principal investigator (PI)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J; EASL Panel of Experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001 Sep;35(3):421-30. doi: 10.1016/s0168-8278(01)00130-1. No abstract available.

  PMID: 11592607 BACKGROUND

• Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.

  PMID: 19474385 BACKGROUND

• Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg. 1999 Jul;189(1):1-7. doi: 10.1016/s1072-7515(99)00075-7.

  PMID: 10401733 BACKGROUND

• Davis JL, Pandalai P, Ripley RT, Langan RC, Steinberg SM, Walker M, Toomey MA, Levy E, Avital I. Regional chemotherapy in locally advanced pancreatic cancer: RECLAP trial. Trials. 2011 May 19;12:129. doi: 10.1186/1745-6215-12-129.

  PMID: 21595953 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Udo Rudloff
• Organization: National Cancer Institute

udo_rudloff@nih.gov

301-496-3098

Study Officials

• Udo Rudloff, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 10, 2011
• First Posted: February 11, 2011
• Study Start: January 26, 2011
• Primary Completion: July 23, 2014
• Study Completion: July 23, 2014
• Last Updated: November 13, 2019
• Results First Posted: October 1, 2018

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)