ADH-1, Gemcitabine Hydrochloride and Cisplatin in Treating Patients With Metastatic Pancreatic or Biliary Tract Cancer That Cannot Be Removed By Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by University of Nebraska
Sponsor:
Collaborators:
Adherex Technologies, Inc.
Information provided by (Responsible Party):
Jean Grem, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01825603
First received: March 27, 2013
Last updated: May 7, 2013
Last verified: May 2013
  Purpose

This phase I trial studies the side effects and best dose of ADH-1 when given together with gemcitabine hydrochloride and cisplatin in treating patients with metastatic pancreatic or biliary tract cancer that cannot be removed by surgery. ADH-1 may stop the growth of cancer cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ADH-1 together with gemcitabine hydrochloride and cisplatin may kill more tumor cells.


Condition Intervention Phase
Acinar Cell Adenocarcinoma of the Pancreas
Adenocarcinoma of the Gallbladder
Adult Primary Cholangiocellular Carcinoma
Advanced Adult Primary Liver Cancer
Cholangiocarcinoma of the Gallbladder
Duct Cell Adenocarcinoma of the Pancreas
Localized Unresectable Adult Primary Liver Cancer
Periampullary Adenocarcinoma
Recurrent Adult Primary Liver Cancer
Recurrent Gallbladder Cancer
Recurrent Pancreatic Cancer
Stage II Gallbladder Cancer
Stage III Pancreatic Cancer
Stage IIIA Gallbladder Cancer
Stage IIIB Gallbladder Cancer
Stage IV Pancreatic Cancer
Stage IVA Gallbladder Cancer
Stage IVB Gallbladder Cancer
Drug: ADH-1
Drug: cisplatin
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of ADH-1 and Gemcitabine Plus Cisplatin in Patients With Unresectable or Metastatic Pancreatic and Biliary Tract Cancers

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Maximum tolerated dose of ADH-1 when given in combination with gemcitabine hydrochloride and cisplatin determined by dose limiting toxicities (DLT), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    The incidence rates of adverse events will be described by dose level. The frequency of occurrence of overall toxicity, categorized by toxicity grades, will be described.


Secondary Outcome Measures:
  • Changes in the levels of ICAM-1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Summarized using descriptive statistics

  • Progression-free survival [ Time Frame: From the first date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    Plotted following the method of Kaplan and Meier.

  • Survival [ Time Frame: From the first date of therapy until the date of death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    Plotted following the method of Kaplan and Meier.

  • Changes in the levels of E-selectin [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Summarized using descriptive statistics.

  • Changes in the levels of VEGF [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Summarized using descriptive statistics.

  • Changes in the levels of soluble VEGFR [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Summarized using descriptive statistics

  • Changes in the levels of B-FGF [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Summarized using descriptive statistics


Estimated Enrollment: 24
Study Start Date: April 2013
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ADH-1, cisplatin, gemcitabine hydrochloride)
Patients receive ADH-1 IV over 20-80 minutes on days 1, 4, 8, 11, 15, and 18, cisplatin IV and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responsive disease may receive maintenance therapy with cisplatin and gemcitabine hydrochloride.
Drug: ADH-1
Given IV
Other Name: Exherin
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the toxicities and determine the recommended dose of ADH-1 given twice weekly for 3 weeks in combination with cisplatin and fixed-dose rate gemcitabine (gemcitabine hydrochloride) given on weeks 1 and 2 of the 3 week schedule for 3 cycles in patients with locally advanced or metastatic pancreatic or biliary tract adenocarcinomas.

SECONDARY OBJECTIVES:

I. To evaluate changes in the levels of intercellular adhesion molecule 1 (ICAM-1), E-selectin, vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor (VEGFR) and basic fibroblast growth factor (B-FGF) during therapy with ADH-1, cisplatin and gemcitabine.

II. Radiographic assessment of disease status after 3 cycles of chemotherapy with ADH-1, cisplatin and gemcitabine.

III. To evaluate progression-free and overall survival of patients with locally advanced or metastatic pancreatic or biliary tract adenocarcinomas treated with ADH-1 given with cisplatin and fixed dose rate gemcitabine for 3 cycles. Patients with stable or responsive disease after 3 cycles will continue on maintenance cisplatin and fixed dose rate gemcitabine.

OUTLINE:

Patients receive ADH-1 intravenously (IV) over 20-80 minutes on days 1, 4, 8, 11, 15, and 18, cisplatin IV and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responsive disease may receive maintenance therapy with cisplatin and gemcitabine hydrochloride.

After completion of study treatment, patients are followed up every 3 months for 2 years.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have adenocarcinoma of the pancreas or biliary tree (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder or ampulla of Vater) that is locally advanced, but non-resectable, metastatic or residual disease after attempted surgical resection
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or better
  • Absolute neutrophil count (ANC) of 2000 per mcL or higher
  • Platelet count of 100,000 per mcL or higher
  • Patients must have a serum creatinine that is at or below the upper limits of the institutional normal range OR a creatinine clearance of 60 mL per min or higher corrected for body surface area (BSA)
  • The total bilirubin must be at or below 2.0 mg/dL in the absence of biliary obstruction; if the patient has biliary obstruction, biliary decompression will be required; either endoscopic placement of a biliary stent or percutaneous transhepatic drainage is acceptable; once biliary drainage has been established, institution of protocol therapy may proceed when the total bilirubin falls to 3.0 mg/dL or lower
  • Patients need not have measurable disease for this study
  • The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
  • Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment
  • Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study; (no childbearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries)

Exclusion Criteria:

  • Patients may not have received prior chemotherapy for metastatic adenocarcinoma of the pancreas or biliary tract; prior adjuvant chemotherapy is acceptable provided that 6 months or longer has elapsed since completion of the prior therapy
  • History of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
  • Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety
  • Pregnant and nursing women are excluded from this study because the chemotherapy agents have the potential for teratogenic or abortifacient effects
  • Patients with prior malignancy will be excluded except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years
  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: NCT01825603

Contacts
Contact: Beth Kos, RN BSN OCN 402-559-4726 mekos@unmc.edu
Contact: Marsha Ketcham, RN OCN 402-559-5286 mketcham@unmc.edu

Locations
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-6805
Contact: Jean L. Grem    800-999-5465    jgrem@unmc.edu   
Principal Investigator: Jean L. Grem         
Sponsors and Collaborators
University of Nebraska
Adherex Technologies, Inc.
Investigators
Principal Investigator: Jean Grem University of Nebraska
  More Information

No publications provided

Responsible Party: Jean Grem, MD, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT01825603     History of Changes
Other Study ID Numbers: 470-12, NCI-2013-00406, P50CA127297
Study First Received: March 27, 2013
Last Updated: May 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Liver Neoplasms
Cholangiocarcinoma
Gallbladder Neoplasms
Biliary Tract Neoplasms
Carcinoma, Acinar Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Liver Diseases
Biliary Tract Diseases
Gallbladder Diseases
Gemcitabine
Cisplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 18, 2014