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

Primary Purpose

Pancreatic Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Chemotherapy

Chemotherapy + ChemoRadiotherapy

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Florida Shands Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Chemotherapy

Chemotherapy and ChemoRadiotherapy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Biochemical Response Rate

Biochemical response rate (serum CA 19-9). Baseline compared to pre-operative serum CA19-9 values.

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.

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.

Secondary Outcome Measures

90 Day Post-operative Mortality

Evaluate mortality in the first 90 days after surgery

Full Information

NCT ID

NCT01470417

First Posted

November 9, 2011

Last Updated

August 18, 2023

Sponsor

University of Florida

1. Study Identification

Unique Protocol Identification Number

NCT01470417

Brief Title

Gemcitabine With Abraxane and Other Investigational Therapies in Neoadjuvant Treatment of Pancreatic Adenocarcinoma

Acronym

GAIN-1

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Completed

Study Start Date

October 2011 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

October 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Florida

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Chemotherapy

Arm Type

Active Comparator

Arm Description

Arm Title

Chemotherapy and ChemoRadiotherapy

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Chemotherapy

Other Intervention Name(s)

Abraxane, Gemcitabine

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Chemotherapy + ChemoRadiotherapy

Other Intervention Name(s)

Abraxane, Gemcitabine

Intervention Description

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.

Primary Outcome Measure Information:

Title

Biochemical Response Rate

Description

Biochemical response rate (serum CA 19-9). Baseline compared to pre-operative serum CA19-9 values.

Time Frame

4 - 8 weeks after neoadjuvant therapy

Title

Radiographic Response Rate

Description

Time Frame

4 - 8 weeks after neoadjuvant therapy

Title

Pathologic Downstaging and Margin Status

Description

Time Frame

At the time of surgery after neoadjuvant therapy

Secondary Outcome Measure Information:

Title

90 Day Post-operative Mortality

Description

Evaluate mortality in the first 90 days after surgery

Time Frame

90 days after surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas George, MD, FACP

Organizational Affiliation

University of Florida

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Florida Shands Cancer Center

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32610

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Gemcitabine With Abraxane and Other Investigational Therapies in Neoadjuvant Treatment of Pancreatic Adenocarcinoma

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