Clinical trial NCT01921751
Conditions: Pancreatic Adenocarcinoma Stage III Pancreatic Cancer
Keywords: SMAD4 IMRT gemcitabine high-dose radiotherapy
Sponsor: Radiation Therapy Oncology Group
Start date: 2013-08-01; Completion date: 2016-06-01
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized phase II trial studies how well high or standard intensity radiochemotherapy after gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) work compared with gemcitabine hydrochloride and nab-paclitaxel alone in treating patients with pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as capecitabine, may make tumor cells more sensitive to radiation therapy. Giving radiation therapy in different ways and adding chemotherapy may kill more tumor cells. It is not yet known whether high intensity radiochemotherapy after gemcitabine hydrochloride and nab-paclitaxel is more effective than standard intensity radiochemotherapy after gemcitabine hydrochloride and nab-paclitaxel or gemcitabine hydrochloride and nab-paclitaxel alone in treating pancreatic cancer.

Detailed description:
PRIMARY OBJECTIVES:

* I. To determine if intensified radiochemotherapy following gemcitabine and nab-paclitaxel in patients with unresectable pancreatic cancer will show a signal for improved 2-year overall survival (OS) from 10% to 22.5% as compared to chemotherapy with gemcitabine and nab-paclitaxel alone.
* II. To determine if standard radiochemotherapy, following gemcitabine and nab-paclitaxel, in patients with unresectable pancreatic cancer will show a signal for improved 2-year OS from 10% to 22.5% as compared to chemotherapy with gemcitabine and nab-paclitaxel alone.

SECONDARY OBJECTIVES:

* I. To evaluate patterns of failure (local and systemic progression) by SMAD family member 4 (SMAD4) status and intensity of radiation therapy.
* II. To evaluate the impact of radiochemotherapy on OS for the subset of SMAD4 intact patients.
* III. To evaluate adverse events associated with the treatments.
* IV. To evaluate correlation between SMAD4 status determined by immunohistochemistry (IHC) and genetic SMAD4 status.

Patients are randomized to 1 of 3 treatment arms.

After completion of study treatment, patients are followed up at 1 month and then every 3 months.

Arms: arm 1: Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent high intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity arm 2: Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent low intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity arm 3: Gemcitabine and nab-paclitaxel until progression or unacceptable toxicity \[randomized to this arm after 3rd cycle and no progression\]
Interventions: intervention 1: low intensity radiation therapy intervention 2: Capecitabine intervention 3: Gemcitabine intervention 4: high intensity radiation therapy intervention 5: nab-Paclitaxel
Intervention descriptions: intervention 1: 50.4 Gy in 28 1.8 Gy fractions (IMRT or 3D-CRT), 5 days/week, starting 3-5 weeks after the last dose of induction chemotherapy intervention 2: 825 mg/m2 PO twice daily, 5 days/week, beginning on the first day of radiation therapy and ending on the last day of radiation therapy. intervention 3: 1000 mg/m2 weekly as a 30 minute infusion after nab-Paclitaxel, three weeks on and 1 week off \[1 cycle = 4 weeks\] intervention 4: 63 Gy intensity-modulated radiation therapy (IMRT) in 28 2.25 Gy fractions, 5 days/week, starts 3-5 weeks after the last dose of induction chemotherapy intervention 5: 125 mg/m2 weekly as a 30-40 minute infusion, three weeks on and 1 week \[1 cycle = 4 weeks\]

Protocol documents: