A Phase II Study of Combine Modality Therapy in Locally Advanced Pancreatic Cancer
Recruitment status was Recruiting
|First Received Date ICMJE||September 7, 2005|
|Last Updated Date||May 16, 2007|
|Start Date ICMJE||October 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
||total of 45 patients are enrolled or until 14 responses are observed.|
|Change History||Complete list of historical versions of study NCT00149578 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||The secondary end points are to evaluate the distant metastasis rate and time to tumor progression, overall survival time and quality of life after induction|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||A Phase II Study of Combine Modality Therapy in Locally Advanced Pancreatic Cancer|
|Official Title ICMJE||A Phase II Study of Induction Chemotherapy Followed by Concurrent Chemotherapy With Radiotherapy in Locally Advanced Pancreatic Cancer|
Induction chemotherapy will be administered every 2 weeks for 6 cycles (about 3 months). Patients who have radiological evidence of progressive disease will be shifted to salvage chemotherapy. Patients who have responsive or stable disease after induction chemotherapy will receive concurrent chemoradiotherapy 3-4 weeks after the last dose of induction chemotherapy. Surgical evaluation will be performed 4-6 weeks after the completion of chemoradiotherapy. Patients who have resectable disease will undergo surgical resection. Postoperative adjuvant chemotherapy with GOFL for 6 cycles will be given for those who have curative resection. Patients who still have unresectable disease or non-curative resection will receive systemic chemotherapy of GOFL till disease progression or unacceptable toxicity.
Induction chemotherapy will be administered on a biweekly basis. Reported adverse events and potential risks for gemcitabine, oxaliplatin, 5-FU and leucovorin are described in Section 6. Appropriate dose modifications for are described in Section 5. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's malignancy.
4.1.1 Treatment schedule of induction chemotherapy
For each dose of GOFL chemotherapy, intravenous infusion of gemcitabine at a fixed rate of 10 mg/m2/min will be immediately followed by a 2-hour intravenous infusion of oxaliplatin and then a 48-hour intravenous infusion of 5-FU and leucovorin.
4.1.2 Premedication before chemotherapy
Patients will receive 4mg of dexamethasone and anti-histamine and appropriate anti-emetics (serotonin antagonists) before each dose of chemotherapy.
4.2 Supportive Care Guidelines
Prophylactic G-CSF or GM-CSF will not be routinely used in this study. In case of febrile neutropenia, patients should be treated with appropriate antibiotics. Therapeutic G-CSF may be used at the discretion of attending physicians
4.3 Duration of Induction Chemotherapy
In the absence of treatment delays due to adverse events, treatment may continue for 6 cycles or until one of the following criteria applies:
C Disease progression, C Intercurrent illness that prevents further administration of treatment, C Unacceptable adverse events(s), C Patient decides to withdraw from the study, or C General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.
4.4 Agents and Radiation Administration during Concurrent Chemoradiotherapy
4.4.1 Treatment schedule during concurrent chemoradiotherapy
126.96.36.199 Patient selection
Patients were evaluated after 6 cycles of induction chemotherapy. Patients who have progressive disease either due to distant metastasis or locoregional progression will be given salvage systemic chemotherapy and will not be enrolled into concurrent chemoradiotherapy. Patients who achieve complete remission, partial remission or stable disease will be enrolled into 2nd phase of the study, concurrent chemoradiotherapy, 3-4 weeks after the last dose of induction chemotherapy.
4.4.2 Study Agents
Gemcitabine 400mg/m2 will be dissolved in 250ml normal saline and infused intravenously at a fixed rate of 10mg/m2/min for 40 mins.
188.8.131.52 Treatment schedule
Gemcitabine 400mg/m2 in 250ml normal saline will be iv infused for 40mins, 2hrs before RT on day 1, 8, 15, 22, 29, 36. Radiation will be given 180cGy per day, 5 days a week for 28 fractions to totally 5040cGy.
184.108.40.206 Premedication for concurrent chemoradiotherapy
Patients were given dexamethasone 2mg orally three times a day (tid) from the morning of their first radiotherapy fraction. The prophylactic dexamethasone will be continued until after they had received their fifth radiation treatment. Therefore, depending on the day of the week the patients started treatment, dexamethasone will be taken for 5 to 7 days. All patients will be issued with rescue medication, prochlorperazine 10mg every 6 hours orally if they develop nausea and vomiting. If patients still have nausea and/or vomiting during treatment of dexamethasone and prochlorperazine or after the fifth day of radiotherapy, ondansetron 8mg orally or iv one to three times per day or granisetron 1mg per os or iv once everyday 30mins before radiotherapy should be given.
220.127.116.11 Radiation technique
Radiation should be performed by high-energy linear accelerators. Three-dimensional radiation treatment planning was used in all cases. Patients will be immobilized in a foam cradle in a supine position, and the treatment planning CT was obtained. Tumor mapping should be performed according to treatment planning CT and the diagnostic CT before induction chemotherapy. Treatment planning was performed with the isocenter calculated at 100% and the 95% line encompassing the planning target volume. The spinal cord was limited to 4600cGy. If one kidney was to receive more than 20Gy then more than 90% of the remaining kidney was excluded from the primary beam. Generally, a three-field no-axial beam arrangement (opposed lateral with an anterior-inferior oblique) was used.
18.104.22.168 Radiation volume
The gross tumor volume is the primary tumor identifiable on CT scan before induction chemotherapy. The clinical target volume was defined as the gross tumor volume plus 0.5cm. The planning target volume was the clinical target volume plus 0.5cm for daily patient set-up variation. No prophylactic nodal irradiation will be given.
22.214.171.124 Radiation dosage
A total dose of 5040cGy in 28 fractions, 180cGy per fraction, one fraction per day, 5 days per week, will be given.
4.5.1 Surgical evaluation
Patients completed induction chemotherapy and concurrent chemoradiotherapy will be evaluated for surgical resection. If there is evidence of distant metastasis, surgery will not be arranged. The feasibility of surgical resection will be evaluated by qualified surgeon according to contrast-enhanced abdominal CT or MRI. Laparoscope is optional for pre-surgical evaluation.
126.96.36.199 Resectable l No distant metastases l Clear fat plane around celiac and superior mesenteric arteries (SMA) l Patent superior mesenteric vein (SMV)/portal vein 188.8.131.52 Borderline resectable l Severe unilateral SMV/portal impingement l Tumor abutment on SMA l Gastroduodenal artery (GDA) encasement up to origin at hepatic artery l Colon or mesocolon invasion l Adrenal, colon or mesocolon, or kidney invasion 184.108.40.206 Unresectable l Distant metastases l SMA, celiac encasement l SMV/portal occlusion l Aortic, inferior vena cava (IVC) invasion or encasement l Invasion of SMV below transverse mesocolon l Rib, vertebral invasion
4.5.2 Treatment schedule of surgery
Surgery will be performed within 4-6 weeks after chemoradiotherapy complete.
4.5.3 Surgical technique
Patients whose tumor are considered to be resectable will undergo laparotomy. If complete surgical resection is feasible, optimal surgery will be performed. If complete surgical resection is impossible, biopsy with or without palliative surgery (eg. bypass surgery) may be performed. 4.6 Adjuvant/Maintenance Chemotherapy
4.6.1 Treatment schedule
Patients who have curative surgical resection will receive 6 cycles of adjuvant GOFL chemotherapy within 4 weeks after surgery and then followed up until tumor progression. Patients who are not feasible for curative resection, will receive continued chemotherapy of GOFL 3-4 weeks after chemoradiotherapy complete. The regimen will continue till disease progression. Patients who develop progressive disease during GOFL will shift to salvage chemotherapy.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Pancreatic Cancer|
|Intervention ICMJE||Drug: Gemcitabine Oxaliplatin 5FU and Leucovorin|
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||45|
|Estimated Completion Date||October 2008|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||20 Years to 75 Years|
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||Taiwan|
|NCT Number ICMJE||NCT00149578|
|Other Study ID Numbers ICMJE||T1204|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Health Research Institutes, Taiwan|
|Information Provided By||National Health Research Institutes, Taiwan|
|Verification Date||May 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP