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Nab-paclitaxel and Gemcitabine Hydrochloride Followed by Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

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ClinicalTrials.gov Identifier: NCT02427841
Recruitment Status : Recruiting
First Posted : April 28, 2015
Last Update Posted : August 31, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Gina Vaccaro, OHSU Knight Cancer Institute

Brief Summary:
This phase II trial studies how well nab-paclitaxel and gemcitabine hydrochloride followed by radiation therapy before surgery work in treating patients with pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as nab-paclitaxel and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving nab-paclitaxel, gemcitabine hydrochloride, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Condition or disease Intervention/treatment Phase
Pancreatic Adenocarcinoma Resectable Pancreatic Carcinoma Drug: Fluorouracil Drug: Gemcitabine Hydrochloride Radiation: Image Guided Radiation Therapy Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Drug: Nab-paclitaxel Procedure: Therapeutic Conventional Surgery Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the R0 (complete resection) resection rate for subjects with borderline resectable or lymph node positive pancreatic adenocarcinoma treated with a multimodality neoadjuvant therapy of preoperative gemcitabine (gemcitabine hydrochloride) and ABRAXANE (nab-paclitaxel) followed by 5-fluorouracil (fluorouracil) based image-guided intensity-modulated radiation therapy (IG-IMRT) chemoradiotherapy.

SECONDARY OBJECTIVES:

I. To determine 1-year relapse-free survival rate with the investigational protocol.

II. To determine 1-year and 2-year overall survival rates. III. To assess response rate by imaging (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) and pathologic analysis.

IV. To assess the toxicity and safety according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) criteria.

OUTLINE:

PRE-OPERATIVE (NEOADJUVANT) CHEMOTHERAPY: Patients receive nab-paclitaxel intravenously (IV) over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo IG-IMRT 5 days a week for 28 fractions and receive fluorouracil IV continuously on days 1-7 for 6 weeks.

SURGICAL RESECTION: Patients undergo surgery 4-10 weeks after the last dose of chemoradiation.

POST-OPERATIVE (ADUJUVANT) CHEMOTHERAPY: Beginning within 8-12 weeks after surgery, patients receive nab-paclitaxel IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4 additional courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 3 years and then every 24 weeks for 2 years.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study of Preoperative Chemotherapy With Abraxane and Gemcitabine Followed by Chemoradiation for Borderline Resectable or Node-Positive Pancreatic Cancer
Actual Study Start Date : January 21, 2016
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : June 1, 2020


Arm Intervention/treatment
Experimental: Treatment (chemotherapy, chemoradiation therapy, surgery)

PRE-OPERATIVE (NEOADJUVANT) CHEMOTHERAPY: Patients receive nab-paclitaxel IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo IG-IMRT 5 days a week for 28 fractions and receive fluorouracil IV continuously on days 1-7 for 6 weeks.

SURGICAL RESECTION: Patients undergo surgery 4-10 weeks after the last dose of chemoradiation.

POST-OPERATIVE (ADUJUVANT) CHEMOTHERAPY: Beginning within 8-12 weeks after surgery, patients receive nab-paclitaxel IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4 additional courses in the absence of disease progression or unacceptable toxicity.

Drug: Fluorouracil
Given IV
Other Names:
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fluracil
  • 5-FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluracil
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011

Radiation: Image Guided Radiation Therapy
Undergo IG-IMRT
Other Names:
  • IGRT
  • image-guided radiation therapy

Radiation: Intensity-Modulated Radiation Therapy
Undergo IG-IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Nab-paclitaxel
Given IV
Other Names:
  • ABI 007
  • ABI-007
  • Abraxane
  • Albumin-bound Paclitaxel
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • Nanoparticle Albumin-bound Paclitaxel
  • nanoparticle paclitaxel
  • paclitaxel albumin-stabilized nanoparticle formulation
  • protein-bound paclitaxel

Procedure: Therapeutic Conventional Surgery
Undergo surgery




Primary Outcome Measures :
  1. R0 resection rate defined as macroscopically complete tumor removal with negative microscopic surgical margins by pathologic assessment [ Time Frame: At the time of surgery ]
    The R0 resection rate will be computed with 95% confidence interval. A 2-sided binomial test will be used to determine whether the R0 resection rate is significantly greater than 0.37 at 10% significance level.


Secondary Outcome Measures :
  1. Incidence of toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 [ Time Frame: Up to 5 years ]
    Frequency and severity of adverse events will be tabulated based on the actual treatment and the number of courses the patient receives. In particular, grade 3 and 4 toxicity rates will be computed and summarized for all patients received at least one dose of the assigned treatment.

  2. Overall survival defined as the percentage of subjects alive at the 2 year time point [ Time Frame: At 2 years ]
    The expected 2-year overall survival rate will be reported with an associated 95% confidence interval. In addition, the overall survival function will be estimated and displayed using a Kaplan Meier curve. The median overall survival will also be estimated with an associated 95% confidence interval.

  3. Overall survival defined as the percentage of subjects alive at the one year time point [ Time Frame: At 1 year ]
    The expected 1-year overall survival rate will be reported with an associated 95% confidence interval. In addition, the overall survival function will be estimated and displayed using a Kaplan Meier curve. The median overall survival will also be estimated with an associated 95% confidence interval.

  4. Relapse-free survival defined as the percentage of subjects who are without recurrence or death at one year from surgical resection of the primary tumor [ Time Frame: At 1 year ]
    The expected 1-year relapse-free survival rate will be reported with an associated 95% confidence interval. In addition, the relapse-free survival function will be estimated and displayed using a Kaplan Meier curve. The median relapse-free survival will also be estimated with an associated 95% confidence interval.

  5. Response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined as the number of subjects with complete or partial disease response as confirmed through tumor imaging with computed tomography (CT) [ Time Frame: After completion of neoadjuvant chemoradiotherapy ]
    The expected pathologic response rate will be computed with the associated 95% confidence interval using binomial exact method.

  6. Serum CA 19-9 levels [ Time Frame: Up to 5 years ]
    Logistic regression will be conducted to associate the serum CA 19-9 levels with response, and Cox proportional hazard regression will be used to associate the serum CA 19-9 expression with overall survival endpoints.

  7. SPARC expression levels [ Time Frame: Up to 5 years ]
    Logistic regression will be conducted to associate SPARC expression with response, and Cox proportional hazard regression will be used to associate SPARC expression with overall survival endpoints.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have histologically or cytologically confirmed adenocarcinoma of the pancreas
  • Tumors must be localized (non-metastatic) and classified as borderline resectable according to Americas Hepato-Pancreato-Biliary Association (AHPBA)/Society of Surgical Oncology (SSO)/Society for Surgery of the Alimentary Tract (SSAT) consensus criteria or be clinically node-positive via computed tomography (CT) or endoscopic ultrasound

    • AHPBA/SSO/SSAT criteria (any one of the following):

      • Tumor-associated deformity of the SMV (superior mesenteric vein) or PV (portal vein)
      • Abutment of the SMV or PV >= 180 degrees
      • Short-segment occlusion of the SMV or PV amenable to resection and venous reconstruction
      • Short-segment involvement of the hepatic artery or its branches amenable to resection and reconstruction
      • Abutment of the superior mesenteric artery (SMA) < 180 degrees
  • Subjects must have measurable disease (by RECIST 1.1), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
  • No prior therapy for pancreatic cancer, including chemotherapy, radiation therapy, definitive surgery or investigational therapy
  • Members of all races and ethnic groups will be included
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Absolute neutrophil count >= 1.5 K/cu mm
  • Platelets >= 100 K/cu mm
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 1.25 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min
  • No active prior malignancy within 3 years of registration (with the exception of non-melanoma skin cancer, in-situ cancers, or Rai stage 0 chronic lymphocytic leukemia [CLL]); if patient is disease free from a prior malignancy between 3-5 years, special consideration can be requested; in these cases, if the risk of recurrence at 5 years is less than 20%, and in the opinion of the investigator the prior malignancy will not affect the patient's outcome in light of newly diagnosed pancreatic cancer, the patient may be eligible; this will require principle investigator (PI) review and approval on a case by case basis, and approval will be documented in the medical record; all patients who have been disease free from a prior malignancy for at least 5 years will be eligible
  • No baseline peripheral sensory neuropathy >= grade 2
  • Women of child-bearing potential and men must be willing to use adequate contraception during the entire study and for 8 weeks following completion of all chemotherapy on study; this includes hormonal or barrier method, or abstinence
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Subjects with locally advanced, unresectable primary tumors will not be eligible

    • This includes any of the following:

      • Abutment of the SMA >= 180 degrees
      • Occlusion of the SMV or PV with insufficient normal vein above and below with which to perform venous reconstruction
      • Involvement of the hepatic artery with insufficient artery proximal and distal to perform reconstruction
  • Any prior therapy (chemotherapy, radiation or surgery) for pancreatic adenocarcinoma other than biliary decompression
  • Subjects who are receiving any other investigational agents
  • Subjects with known metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABRAXANE or other agents used in the study
  • Active infection requiring intravenous antibiotics at the time of registration
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • History of interstitial lung disease, idiopathic pulmonary fibrosis, silicosis, sarcoidosis or connective tissue disorders (including rheumatoid arthritis and systemic lupus erythematosus)
  • Pregnant or breastfeeding women are excluded from this study
  • Subjects known to be human immunodeficiency virus (HIV)-positive, including those on combination antiretroviral therapy, are ineligible
  • Subjects with plastic biliary stents will be excluded; metal biliary stents are allowed and will not be excluded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02427841


Locations
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United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Gina M. Vaccaro    503-260-7593    vaccarog@ohsu.edu   
Principal Investigator: Gina M. Vaccaro         
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Gina Vaccaro OHSU Knight Cancer Institute

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Responsible Party: Gina Vaccaro, Principal Investigator, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT02427841     History of Changes
Other Study ID Numbers: IRB00011256
NCI-2015-00498 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
SOL-14124-L
MR00045490
IRB00011256 ( Other Identifier: OHSU Knight Cancer Institute )
P30CA069533 ( U.S. NIH Grant/Contract )
First Posted: April 28, 2015    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Pancreatic Diseases
Adenocarcinoma
Carcinoma
Digestive System Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Fluorouracil
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs