Clinical trial NCT00408564: Cetuximab, Gemcitabine, and Oxaliplatin Followed By Surgery or External-Beam Radiation Therapy and Capecitabine in Treating Patients With Locally Advanced, Nonmetastatic Pancreatic Cancer That Cannot Be Removed By Surgery
Official title: Phase II Study of Neoadjuvant Gemcitabine/Oxaliplatin and Cetuximab Followed by Surgery or Concurrent External Beam Radiation With Capecitabine for Patients With Locally Advanced Unresectable Nonmetastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
stage II pancreatic cancer
stage III pancreatic cancer
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2006-12-07
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as gemcitabine, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving cetuximab together with chemotherapy may reduce drug resistance and allow the tumor cells to be killed. Giving cetuximab and chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with oxaliplatin and gemcitabine followed by surgery or external-beam radiation therapy and capecitabine works in treating patients with locally advanced, nonmetastatic pancreatic cancer that cannot be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* Determine the progression-free survival rate in patients with unresectable, locally advanced, nonmetastatic adenocarcinoma of the pancreas treated with neoadjuvant therapy comprising cetuximab, gemcitabine hydrochloride, and oxaliplatin followed by either surgery or chemoradiotherapy comprising external-beam radiotherapy and capecitabine.

Secondary

* Determine the toxicity and tolerability of this regimen in these patients.
* Determine overall survival and progression-free survival.
* Determine the response rate in these patients.
* Determine the response duration (defined as the time from first observation response to the time of progressive disease) in patients who achieve at least a partial response to treatment.
* Determine the biomarker response of CA19-9.

OUTLINE: This is an open-label study.

* Neoadjuvant therapy: Patients receive cetuximab IV over 1-2 hours on days 1 and 8, gemcitabine hydrochloride IV over 100 minutes on day 1, and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are evaluated after completion of neoadjuvant therapy. Patients with metastatic disease are taken off study. Beginning within 4 weeks after completion of neoadjuvant therapy, patients with resectable disease proceed to surgical resection or chemoradiotherapy (by choice); patients with unresectable disease proceed to chemoradiotherapy.

* Surgery: Patients undergo surgical resection with the Whipple procedure.
* Chemoradiotherapy: Patients receive oral capecitabine twice daily 5 days a week (on days 1-5) and undergo external-beam radiotherapy once daily 5 days a week for 5½ weeks.

After completion of study treatment, patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or radiologically confirmed pancreatic cancer, meeting both of the following criteria:

  * Locally advanced, nonmetastatic disease
  * Surgically unresectable disease
* Measurable disease, defined as unidimensionally measurable by physical exam or imaging study

  * The following are considered nonmeasurable disease:

    * Bone-only disease
    * Pleural or peritoneal effusions
    * CNS lesions
    * Irradiated lesions in the absence of progression after radiotherapy
* No history or evidence of CNS disease
* No metastatic disease to distant organs (e.g., liver, lung, brain, or bone)

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Granulocyte count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Bilirubin ≤ 2.0 mg/dL
* Creatinine ≤ 2.0 mg/dL
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 90 days after completion of study therapy
* No acute hepatitis
* No known HIV positivity
* No active or uncontrolled infection
* No significant history of uncontrolled cardiac disease, including, but not limited to, any of the following:

  * Uncontrolled hypertension
  * Unstable angina
  * Myocardial infarction within the past 6 months
  * Uncontrolled congestive heart failure
  * Cardiomyopathy with decreased ejection fraction
* No prior severe infusion reaction to a monoclonal antibody
* No active second malignancy other than nonmelanoma skin cancer
* No history of deep vein thrombosis
* No history of bleeding diathesis or coagulopathy
* No other severe concurrent disease, mental incapacitation, or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

* No prior therapy for pancreatic cancer
* No prior therapy specifically targeting the epidermal growth factor-receptor pathway
* No major surgical procedure or open biopsy within the past 28 days
* No prior radiotherapy or chemotherapy
* No prior or concurrent full-dose anticoagulants or thrombolytics

Primary outcomes:
measure: Progression-free Survival at 6 Months
timeFrame: up to 46 weeks after the start of study treatment
Secondary outcomes:
measure: Number of Participants With Grade 3-4 Adverse Events Reported
timeFrame: from start of study treatment until end of study visit, about 30 weeks
measure: Overall Survival
timeFrame: up to 46 weeks after the start of study treatment
measure: Response Rate
timeFrame: up to 46 weeks after the start of study treatment
measure: Response Duration in Patients With at Least Partial Response to Treatment
timeFrame: up to 46 weeks after the start of study treatment
measure: Determine the Biomarker Response of CA 19-9 to Therapy
timeFrame: from start up treatment to one year after end of treatment, up to 81 weeks
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Andrew S. Kraft, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina, Hollings Cancer Center
name: Gustavo Leone
role: STUDY_CHAIR
References: