Clinical trial NCT02283372: Nab-Paclitaxel Plus Gemcitabine With Concurrent MR-Guided IMRT in Patients With Locally Advanced Pancreatic Cancer
Official title: Prospective Phase I Study of Nab-Paclitaxel Plus Gemcitabine With Concurrent MR-Guided IMRT in Patients With Locally Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2014-11-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A phase I study to evaluate safety of gemcitabine with nab-paclitaxel and concurrent IMRT for locally advanced and borderline resectable pancreatic cancer. The goal of this study is to evaluate if a chemotherapy regimen that provides superior systemic efficacy may be safely delivered and enhance efficacy of tumor directed radiation therapy.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed locally advanced adenocarcinoma of the pancreas that is considered unresectable or borderline resectable based on institutional standardized criteria of unresectability or medical inoperability. Patients with and without regional adenopathy are eligible.
* Prior systemic chemotherapy allowed. It is anticipated and suggested that most patients enrolled on study will have received a minimum of approximately 2 months of systemic therapy according to routine institutional practices. The patient must also be felt by the treating medical oncologist and radiation oncologist to be a candidate for treatment with gemcitabine/nab-paclitaxel chemoradiotherapy.
* At least 18 years of age.
* ECOG performance status ≤ 1
* Normal bone marrow and organ function as defined below:

  * Absolute neutrophil count ≥ 1,000/mcl
  * Platelets ≥ 100,000/mcl
  * Hemoglobin ≥ 9.0 g/dL
  * Total bilirubin ≤ 1.5 x ULN
  * AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN
  * Serum creatinine ≤ 1.5 mg/dL or calculated CrCL\>60mL/min using Cockcroft and Gault formula
* Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
* Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

* Distant metastatic disease, including known brain metastases.
* History of prior malignancy is acceptable, but prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields is not allowed.
* Currently receiving any other investigational agents.
* Major surgery within 4 weeks prior to first study drug administration.
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or nab-paclitaxel or other agents used in the study.
* 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.
* Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14 days of study entry.
* Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with gemcitabine and nab-paclitaxel. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Completion of toxicity follow-up for all patients (up to 32 months)
Secondary outcomes:
measure: Rate of conversion of patients with locally advanced pancreatic cancer or borderline resectable to resectable
timeFrame: 1 year
measure: Local control (Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
timeFrame: 1 year
measure: Progression-free survival (PFS)
timeFrame: 1 year
measure: Overall survival (OS)
timeFrame: 1 year
measure: Quality of life as measured by the EORTC QLQ-C30
timeFrame: 3 months after completion of treatment (up to 18 weeks)
measure: Frequency of RT adaptation based on MR guidance
timeFrame: 3 months after completion of treatment (up to 18 weeks)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Hyun Kim, M.D.
role: PRINCIPAL_INVESTIGATOR
References: