Gemcitabine With Abraxane and Other Investigational Therapies in Neoadjuvant Treatment of Pancreatic Adenocarcinoma (GAIN-1)

GAIN-1 Study: Gemcitabine With Abraxane and Other Investigational Therapies in Neoadjuvant Treatment of Pancreatic Adenocarcinoma

This study will evaluate the role of Gemcitabine and Abraxane in the treatment of resectable and borderline-resectable pancreatic cancer by giving the chemotherapy before surgery.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Chemotherapy; Drug: Chemotherapy + ChemoRadiotherapy

Detailed Description

This current study proposes to conduct a prospective non-randomized open-label phase II trial using Gemcitabine and Abraxane in the neoadjuvant treatment of resectable and borderline-resectable pancreatic cancer. For patients that are low-risk resectable (based on prediction rule) the plan is to administer 2 cycles of Gemcitabine and Abraxane followed by additional systemic therapy or chemotherapy with radiation therapy (chemoRT), followed by surgical resection. For patients who are either borderline-resectable or high-risk resectable (see schema), the plan is to administer 2 cycles of Gemcitabine and Abraxane followed by chemoradiotherapy concurrent with gemcitabine followed by surgical resection. For those without high-risk features, systemic chemotherapy alone will be administered. The primary endpoints will be R0 surgical resection rate, biochemical (CA 19-9), pathologic and radiologic response rates. Secondary endpoints will include progression-free survival (PFS), overall survival (OS), 30-day post-op mortality, toxicity, quality of life, pain control, and correlative molecular exploratory analysis involving pancreatic tumor and stromal SPARC expression levels. The investigators will also assess the patient, tumor, and clinical characteristics that may predict R0 resectability, thus further refining the predictive rule in high-risk patients as defined by Bao and colleagues. The investigators' hypothesis is that by using targeted and risk-adapted chemotherapy or chemoRT, improved R0 surgical resections can be achieved and effective systemic therapy delivered, which will translate to a significant improvement in overall survival in patients with pancreatic adenocarcinoma, compared to published historical controls.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Shands Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• • Histologically or cytologically confirmed adenocarcinoma of the pancreas.

  • Patients must have locally advanced pancreatic cancer, classified as either low-risk resectable (LR), high-risk resectable (HR) or borderline resectable (BR)
  • Age between 18 and 90 years at the time of consent.
  • Patients with biliary obstruction must have adequate drainage prior to starting treatment.
  • Patients must have ≤ Grade I peripheral neuropathy (CTCAE v 4.0)
  • Patients must have ≤ ECOG Performance status 2

  • Pretreatment laboratory parameters:

    • Absolute granulocyte/neutrophil count (AGC/ANC) ≥ 1.8 thou/mm3
    • Platelet count ≥ 100,000/mm3
    • Bilirubin < 2 mg/dl
    • ALT/SGPT < 10x upper limit of normal
    • Creatinine < 3 mg/dl
    • Calculated creatinine clearance (via Cockcroft-Gault) > 30 mL/min
    • Baseline CA 19-9 levels
  • Signed study specific, IRB stamped informed consent

Exclusion Criteria:

• • Evidence of any distant metastasis including peritoneal seeding and/or malignant ascites

  • Previous irradiation to the abdomen that would compromise the ability to deliver the prescribed treatment
  • Prior treatment for pancreatic cancer
  • Active, untreated infection
  • Surgical resection of the tumor (not including biopsies)
  • Other malignancy (except non-melanoma skin cancer) that has not been disease-free for at least 5 years.
  • Pregnant and/or breast-feeding women, or patients (men and women) of child-producing potential not willing to use medically acceptable contraception while on treatment and for at least 3 months thereafter.
  • Use of anti-epileptics (drugs such as phenytoin, phenobarbitol and carbamazepine)
  • ECG abnormality with the following: QTC >500, left bundle branch block or any other clinically significant finding that would interfere with protocol therapy.
  • History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chemotherapy; Individuals with low risk disease will receive nab-paclitaxel 100 mg/m2 IV over 30 minutes on days 1, 8, and 15 along with gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 in an every 28 day cycle for two cycles. Subjects with low risk disease will have an additional two cycles of therapy (4 total cycles) prior to resection.	Drug: Chemotherapy; Nab-paclitaxel 100 mg/m2 IV over 30 minutes on days 1, 8, and 15 along with gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 in an every 28 day cycle for two cycles. Subjects with low risk disease will have an additional two cycles of therapy (4 total cycles) prior to resection.; Other Names: Gemcitabine; Abraxane
Active Comparator: Chemotherapy and ChemoRadiotherapy; Individuals with high-risk disease or borderline resectable disease will receive nab-paclitaxel 100 mg/m2 IV over 30 minutes on days 1, 8, and 15 along with gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 in an every 28 day cycle for two cycles. Subjects with high-risk or borderline resectable disease will receive additional chemotherapy with radiation therapy prior to resection.	Drug: Chemotherapy + ChemoRadiotherapy; Nab-paclitaxel 100 mg/m2 IV over 30 minutes on days 1, 8, and 15 along with gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 in an every 28 day cycle for two cycles. Subjects with high-risk or borderline resectable disease will receive additional chemotherapy with radiation therapy prior to resection.; Other Names: Gemcitabine; Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical Response Rate	Biochemical response rate (serum CA 19-9). Baseline compared to pre-operative serum CA19-9 values.	4 - 8 weeks after neoadjuvant therapy
Radiographic Response Rate	Evaluate radiographic response of the measurable disease with repeat imaging at 4 - 8 weeks after therapy. Measurable disease was evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 criteria. Per RECIST v1.1 in target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >20% growth in the sum of the longest diameter or target lesions or appearance of new lesions; Stable Disease (SD), change in sum of longest diameter of target lesions does not meet criteria for PR or PD. The number of subjects experiencing Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD) is reported.	4 - 8 weeks after neoadjuvant therapy
Pathologic Downstaging and Margin Status	Pathologic stage and margin status after resection. Pathologic downstaging was determined my looking at the rate of R0 (all residual tumor removed during surgery) vs R1 (microscopic tumor present at the resection margin per pathology) resections.	At the time of surgery after neoadjuvant therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90 Day Post-operative Mortality	Evaluate mortality in the first 90 days after surgery	90 days after surgery

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Thomas George, MD, FACP, University of Florida

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: November 9, 2011
• First Submitted That Met QC Criteria: November 10, 2011
• First Posted (Estimated): November 11, 2011

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 18, 2023
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine
• Other Study ID Numbers: IRB201701386 (University of Florida); GAIN-1 (Other Identifier: University of Florida)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No