Chemoradiation With Gemcitabine in Combination With Panitumumab for Patients With Locally Advanced Pancreatic Cancer

NCT01175733 | Completed Phase 1

• 1 other identifier: 20080686
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Keywords

Panitumumab; Chemoradiation; Pancreatic cancer; Locally advanced; Inoperable

Outcome Measures

Primary Outcomes (3)

• Phase I: the recommended safe dosing for the combination of chemoradiation with gemcitabine plus panitumumab.

  During the phase I part of the study, we have planned to study four dose levels of panitumumab if no MTD is being derived before the final dose level. Patients will be enrolled in cohorts of 3 per dose level. If there are no dose-limiting toxicities (DLTs) experienced by the first 3 patients in a cohort during the first 43 days after the first study treatment, additional patients will be entered in the next dose level. At the final dose level recommended for the phase II study a minimum of 6 patients will be treated.

  43 days

• Phase II: the proportion of patients that is alive and progression-free at 7 months.

  For each patient, the time of progression will be recorded. Any patient who discontinues treatment due to adverse reactions, refusal, or who goes on to receive alternate therapy will be considered censored at their last tumor assessment. The sample size was determined based upon a Bryant Day Phase II clinical trial design, taking into account both activity as well as toxicity. The proportion of patients with 7 month PFS will be calculated with exact 95% confidence intervals.

  1 year

• Phase II: safety and tolerability

  Toxicities will be tabulated and summarized overall and across grade and type according to CTC criteria. When grade ≥3 toxicity occurs in ≥ 50% of patients this will be evaluated as unacceptable toxicity according to the two step evaluation design as described. This relatively high percentage of toxicity is based on the details of multiple studies of combination chemoradiation with gemcitabine as given in the introduction.

  1 year

Secondary Outcomes (3)

• Early signs of clinical activity of the combination of chemoradiation with gemcitabine plus panitumumab.

  1 year

• Clinical response rate of the combination of chemoradiation with gemcitabine plus panitumumab.

  1 year

• Time-to-progression (TTP) and overall survival

  1 year

Study Arms (1)

Panitumumab

EXPERIMENTAL

Drug: Panitumumab

Interventions

Panitumumab DRUG

During the first 6 weeks Panitumumab will be administered weekly in combination with radiotherapy plus gemcitabine. From week 8 and further gemcitabine will be administered as monotherapy until disease progression or unacceptable toxicity, for a maximum duration of 1 year.

Panitumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Neutrophils ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hb ≥ 6 mmol/L
• Hepatic function:
• AST/ALT and alkaline phosphatase (ALP) ≤ 2.5 x institutional upper limit of normal (ULN)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Amgen: collaborator

Study Sites (1)

VU University Medical Center

Amsterdam, 1081HV, Netherlands

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Panitumumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Henk MW Verheul, MD, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: August 3, 2010
• First Posted: August 5, 2010
• Study Start: July 8, 2010
• Primary Completion: March 1, 2016
• Study Completion: May 1, 2016
• Last Updated: March 20, 2017

Record last verified: 2017-03

Locations

NL (1)