Paclitaxel and Bryostatin 1 in Treating Patients With Advanced Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00031694
First received: March 8, 2002
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

Phase II trial to study the effectiveness of combining paclitaxel and bryostatin-1 in treating patients who have locally advanced unresectable or metastatic pancreatic cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bryostatin-1 may help paclitaxel kill more cancer cells by making tumor cells more sensitive to the drug.


Condition Intervention Phase
Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer
Drug: paclitaxel
Drug: bryostatin 1
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Sequential Paclitaxel and Bryostatin-1 for Patients With Advanced Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    Associated 95% confidence intervals will be computed and presented.


Secondary Outcome Measures:
  • Toxicity of therapy defined as any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic functions, as indicated by physical signs, symptoms, and/or laboratory changes [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    95% confidence intervals will be computed and presented.

  • Overall survival [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    Computed using the Kaplan-Meier estimator.

  • Bryostatin 1 pharmacokinetics [ Time Frame: Week 1 ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: January 2002
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (paclitaxel, bryostatin 1)
Patients receive paclitaxel IV over 1 hour on day 1 followed by bryostatin 1 IV over 1 hour on day 2 of weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: bryostatin 1
Given IV
Other Names:
  • B705008K112
  • BRYO
  • Bryostatin
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the response rates to weekly, sequential paclitaxel/ bryostatin-1 in patients with unresectable and metastatic pancreatic cancer.

II. To determine the toxicity of therapy. III. To determine patient survival after therapy. IV. To determine Bryoststin-1 pharmacokinetics.

OUTLINE: This is an open-label, multicenter study.

Patients receive paclitaxel IV over 1 hour on day 1 followed by bryostatin 1 IV over 1 hour on day 2 of weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

  Eligibility

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

Inclusion Criteria:

  • Histologic proof of adenocarcinoma of the pancreas confirmed at the pathology department of the enrolling institution; pathologic evidence may include fine needle aspirate material from sites of distant spread (e.g. liver, lymph- nodes, peritoneum) in patients with an unambiguous pancreatic tumor (i.e. a likely pancreatic primary)
  • Pancreatic cancer, which is locally advanced and considered surgically not resectable or metastatic pancreatic cancer
  • Patients with or without prior treatment are eligible for treatment on protocol; prior treatment may have included one treatment course of chemo/RT and/ or one course of chemotherapy, but not two prior courses of chemotherapy; chemotherapy will be defined to include standard cytotoxic treatments, as well as newer biologic agents (eg Herceptin, EGFR antagonist, Ras inhibitors)

    • Chemo/RT: one prior neo-adjuvant, adjuvant or definitive course of chemo/ RT (which did not include a taxane), or RT alone will be allowed
    • one prior course of chemotherapy alone which did not include a taxane
    • Radiotherapy alone
    • Specific sequences of prior treatment permissible for study entry:

      • Chemo/RT
      • RT alone
      • Chemo/RT -> progression -> chemotherapy alone (eg gemcitabine)
      • One course of chemotherapy alone (eg gemcitabine, or chemo combinations)
      • Adjuvant Vaccine -> progression -> chemotherapy alone or chemo/RT
  • Patients must have at least one-dimensionally measurable disease; a lesion is considered measurable if one diameter is >= 20 mm in one dimension by conventional techniques, or >= 10 mm in one dimension by spiral CT; prior radiotherapy is allowable; lesions within the prior field of radiation may only be used as indicator lesions if there has been recent evidence of disease progression at that site, defined as a 50% increase in longest diameter, or 100% increase in the product of two-dimensional radiographic evaluation (eg width x depth) since the completion of radiation therapy
  • ECOG performance status of 0-1
  • Ability to sign an informed consent form indicating awareness of the investigational nature of this study, in keeping with the policies of the hospital
  • Patients may not be receiving any other concurrent chemotherapy, immunotherapy, or radiotherapy; the most recent treatment for pancreatic cancer, within the limitations of allowed prior therapy must be 28 days or longer prior to enrollment on study
  • Absolute granulocytes > 1,500/mm^3
  • Platelets > 150,000/mm^3
  • Serum bilirubin < 1.5 mg/dl
  • Serum creatinine < 1.5 mg/dl

Exclusion Criteria:

  • Presence of any ongoing toxic effect from prior treatment
  • Brain metastases
  • History of active angina or myocardial infarction within 6 months; history of significant ventricular arrhythmia requiring medication with antiarrhythmics; well controlled atrial fibrillation on standard management will be permitted
  • Pregnant or lactating women are ineligible as the effect of the drugs used in this study on a fetus or newborn child is unknown; a pregnancy test will be performed on each fertile premenopausal female prior to entry into the study; treatment may not begin until the results of the pregnancy test are ascertained
  • Pre-existing neurotoxicity that is graded 3+ or greater
  • Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy
  • Psychiatric disorders rendering patients incapable of complying with the requirements of the protocol
  • Any concurrent active malignancy other than non-melanoma skin cancers or carcinoma-in-situ of the cervix; patients with previous malignancies but without evidence of disease for > 5 years will be allowed to enter the trial; patients with a history of a T1a or b prostate cancer (detected incidentally at TURP and comprising less than 5% of resected tissue) may participate if the PSA remained within normal limits since TURP removal
  • Patients with a history of HIV disease; this is based upon the possible interactions of the bryostatin-1 or paclitaxel with anti-retroviral medications or possible immunosuppressive activity of the experimental agents
  • Any other medical condition or reason that, in the investigator's opinion, makes the patient unsuitable to participate in a clinical trial (for example a history of prior poor compliance with treatment)
  • Patients with more than the permitted number of treatments for their pancreas cancer will not be allowed to participate; specific treatment sequences that will exclude patients from study entry are:

    • More than one chemotherapy alone regimen (ie gemcitabine -> progression -> fluorouracil)
    • Any prior treatment with paclitaxel for pancreas cancer
  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: NCT00031694

Locations
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Sponsors and Collaborators
Investigators
Principal Investigator: Andreas Kaubisch Montefiore Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00031694     History of Changes
Other Study ID Numbers: NCI-2012-03003, 01-09-224, NCI-5624, N01CM17103
Study First Received: March 8, 2002
Last Updated: May 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pancreatic Neoplasms
Adenocarcinoma
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
Bryostatin 1
Paclitaxel
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014