Clinical trial NCT01175733: Chemoradiation With Gemcitabine in Combination With Panitumumab for Patients With Locally Advanced Pancreatic Cancer
Official title: Chemoradiation With Gemcitabine in Combination With Panitumumab for Patients With Locally Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: Panitumumab
Chemoradiation
Pancreatic cancer
Locally advanced
Inoperable
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2010-08-05
Enrollment: 18
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: The purpose of this study is to investigate whether the addition of panitumumab to radiotherapy plus gemcitabine will increase the number of patients who are alive and progression free at 7 months.

Detailed description: This is a phase I/II, multi-center dose escalation study.

Phase I:

Patients will be enrolled in cohorts of 3 per dose level until the MTD of panitumumab has been established.

Phase II:

Up to approximately 56 patients will be treated at the MTD level of panitumumab as established in the phase I part of the study.

Based on the historic data of patients with pancreatic cancer treated with gemcitabine based chemoradiation, we aim to increase the number of patients who are alive and progression free at 7 months from the historical value of 50% to 70% with the combination treatment of chemoradiation plus panitumumab.

Eligibility criteria: Inclusion Criteria:

* Histological or cytological confirmed pancreatic cancer.
* Not eligible for curative resection.
* No distant metastases present.
* Previously untreated with chemotherapy and anti-cancer biologicals for current malignancy.
* No other current malignant disease, except for basal cell carcinoma of the skin.
* Measurable or evaluable disease as defined by RECIST 1.1 criteria.
* Performance status 0-2 Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Scale.
* Age ≥ 18 years.
* Adequate haematological and biological functions:

  * Bone marrow function:

    1. Neutrophils ≥ 1.5 x 109/L
    2. Platelets ≥ 100 x 109/L
    3. Hb ≥ 6 mmol/L
  * Hepatic function:

    1. AST/ALT and alkaline phosphatase (ALP) ≤ 2.5 x institutional upper limit of normal (ULN)
    2. Bilirubin ≤ 1.5 times institutional ULN
  * Renal function:

eGFR \>50ml/min

• Metabolic Function:

1. Magnesium ≥ lower limit of normal
2. Calcium ≥ lower limit of normal.

   * No imminent bowel obstruction.
   * No active bleeding.
   * No uncontrolled infection.
   * Patients with reproductive potential must use effective contraception. Female patients must have a negative pregnancy test.
   * Signed informed consent.

Exclusion Criteria:

* Participation in another therapeutic clinical study within 30 days of enrollment or during this clinical study.
* No adequate radiation therapy possible: based on the opinion of the radiation oncologist when radiation therapy cannot be performed because radiation field is too large (PTV volume too large or OAR too high)
* History of allergic reactions to gemcitabine or antibody treatment.
* Presence of any serious concomitant systemic disorders incompatible with the clinical study (e.g. uncontrolled inter-current illness including ongoing or active infection, uncontrolled hypertension).
* Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within 1 year before enrolment/randomization
* History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
* Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance.
* Pregnant or breastfeeding women.
* Absence of adequate contraception for both male and female fertile patients for the duration of the study; and also for six months after last treatment.
* Known positive status for HIV and/or hepatitis B or C.
* Any reason why, in the investigator's opinion, the patient should not participate in the study.
* Drug or alcohol abuse.

Primary outcomes:
measure: Phase I: the recommended safe dosing for the combination of chemoradiation with gemcitabine plus panitumumab.
timeFrame: 43 days
measure: Phase II: the proportion of patients that is alive and progression-free at 7 months.
timeFrame: 1 year
measure: Phase II: safety and tolerability
timeFrame: 1 year
Secondary outcomes:
measure: Early signs of clinical activity of the combination of chemoradiation with gemcitabine plus panitumumab.
timeFrame: 1 year
measure: Clinical response rate of the combination of chemoradiation with gemcitabine plus panitumumab.
timeFrame: 1 year
measure: Time-to-progression (TTP) and overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Henk MW Verheul, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: