Paclitaxel and Bryostatin 1 in Treating Patients With Advanced Pancreatic Cancer

A Phase II Study of Sequential Paclitaxel and Bryostatin-1 for Patients With Advanced Pancreatic Cancer

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.

Study Overview

• Status: Completed
• Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer
• Intervention / Treatment: Drug: paclitaxel; Drug: bryostatin 1

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 Bryostatin-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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologic proof of adenocarcinoma of the pancreas that is locally advanced and considered surgically not resectable or metastatic
• 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;
• Measurable disease
• 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
• 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
• HIV infection
• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Taxol; Anzatax; Asotax; TAX; Drug: bryostatin 1; Given IV; Other Names: B705008K112; BRYO; Bryostatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate of at Least 30%	Number of participants with a Response rate of at least 30%. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST).	Up to 8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events		Up to 8 years
Overall Survival	Computed using the Kaplan-Meier estimator.	Up to 8 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bryostatin 1 Pharmacokinetics	Not done-study terminated early	Week 1

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Andreas Kaubisch, Montefiore Medical Center

Publications and helpful links

General Publications

• Lam AP, Sparano JA, Vinciguerra V, Ocean AJ, Christos P, Hochster H, Camacho F, Goel S, Mani S, Kaubisch A. Phase II study of paclitaxel plus the protein kinase C inhibitor bryostatin-1 in advanced pancreatic carcinoma. Am J Clin Oncol. 2010 Apr;33(2):121-4. doi: 10.1097/COC.0b013e3181a31920.

Study record dates

Study Major Dates

• Study Start: March 1, 2002
• Primary Completion (ACTUAL): April 1, 2010
• Study Completion (ACTUAL): April 1, 2010

Study Registration Dates

• First Submitted: March 8, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (ESTIMATE): January 27, 2003

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms; Carcinoma, Acinar Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Adjuvants, Immunologic; Paclitaxel; Bryostatin 1
• Other Study ID Numbers: NCI-2012-03003; N01CM17103 (U.S. NIH Grant/Contract); 01-09-224 (OTHER: Montefiore Medical Center); NCI-5624 (OTHER: CTEP)