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A randomized multicentre phase II trial comparing adjuvant therapy in patients with interferon alpha-2b and 5-FU alone or in combination with either external radiation treatment and cisplatin (CapRI) or radiation alone regarding event-free survival - CapRI-2.

Märten A, Schmidt J, Ose J, Harig S, Abel U, Münter MW, Jäger D, Friess H, Mayerle J, Adler G, Seufferlein T, Gress T, Schmid R, Büchler MW - BMC Cancer (2009)

Bottom Line: First clinical results are expected for the end of 2009.Primary endpoint is the comparison of the treatment groups with respect to six-month event-free-survival.An event is defined as grade 3 or grade 4 toxicity, objective tumour recurrence, or death.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg 69120, Germany. angela.maerten@med.uni-heidelberg.de

ABSTRACT

Background: The 5-year survival of patients with resected pancreatic adenocarcinoma is still unsatisfying. The ESPAC-1 and the CONKO 001 trial proofed that adjuvant chemotherapy improves 5-year survival significantly from approximately 14% to 21%. In parallel, investigators from the Virginia Mason Clinic reported a 5-year survival rate of 55% in a phase II trial evaluating a combination of adjuvant chemotherapy, immunotherapy and external beam radiation (CapRI-scheme). Two other groups confirmed in phase II trials these results to a certain extent. However, these groups reported severe gastrointestinal toxicity (up to 93% grade 3 or 4 toxicity). In a randomized controlled phase III trial, called CapRI, 110 patients were enrolled from 2004 to 2007 in Germany and Italy to check for reproducibility. Interestingly, much less gastrointestinal toxicity was observed. However, dose-reduction due to haematological side effects had to be performed in nearly all patients. First clinical results are expected for the end of 2009.

Methods/design: CapRI-2 is an open, controlled, prospective, randomized, multicentre phase II trial with three parallel arms. A de-escalation of the CapRI-scheme will be tested in two different modifications. Patients in study arm A will be treated as outpatients with the complete CapRI-scheme consisting of cisplatin, Interferon alpha-2b and external beam radiation and three cycles of 5-fluorouracil continuous infusion. In study arm B the first de-escalation will be realised by omitting cisplatin. Next, patients in study arm C will additionally not receive external beam radiation. A total of 135 patients with pathologically confirmed R0 or R1 resected pancreatic adenocarcinoma are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to six-month event-free-survival. An event is defined as grade 3 or grade 4 toxicity, objective tumour recurrence, or death.

Discussion: The aim of this clinical trial is to evaluate de-escalation of the CapRI-scheme. It is hypothesised that removal of cisplatin and radiotherapy will have no significant effect or only a minor impact on the clinical response but result in substantially lower toxicity.

Trial registration: Current Controlled Trials ISRCTN79802092.

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Treatment scheme.
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Figure 1: Treatment scheme.

Mentions: After implantation of a Port-A-Cath catheter patients will be treated as follows (see figure 1): All arms: 200 mg/m2/day 5-FU by continuous intravenous infusion on days 1–38; 64–101, and 120–161; three million units IFN-α2b subcutaneous three times weekly days 1–38 plus one injection prior to treatment start given during week -1 (approx. day -6). Non-steroidal anti-inflammatory drugs and steroids should be avoided if possible during IFN-α2b treatment. Only arm A and B: Beside 5–FU and IFN-α2b patients will be treated with external beam radiation: The pancreatic bed will be covered with a minimum margin of 2 cm. The porta hepatis, origins of the celiac axis and superior mesenteric artery will be included. The fields must include the entire duodenal C-loop as seen on pre-operative CT scan. Total dose will be 50.4 Gy in 28 fractions over 5.5 weeks (1.8 Gy/day). Simulation should be done with the patient in the supine position with "arms up" position. A treatment planning CT is required to allow 3-D conformal treatment planning. Conventional 3-D treatment techniques as well as intensity modulated radiotherapy (IMRT) could be used for radiotherapy. At least a four field technique for 3-D planning or a multi-field technique for IMRT is necessary. Furthermore a multi-leaf collimator is required to allow customized blocking and IMRT. Equipment: greater than or equal to 6 MeV photons should be used. Only study arm A): Cisplatin 30 mg/m2 IV over 60 minutes on days 1, 8, 15, 22, 29, 36 (6 doses). Two to three hours before and after Cisplatin dose the patients will receive hydration of at least 2 litres. Patients will be taught to drink at least 1 litre during the day.


A randomized multicentre phase II trial comparing adjuvant therapy in patients with interferon alpha-2b and 5-FU alone or in combination with either external radiation treatment and cisplatin (CapRI) or radiation alone regarding event-free survival - CapRI-2.

Märten A, Schmidt J, Ose J, Harig S, Abel U, Münter MW, Jäger D, Friess H, Mayerle J, Adler G, Seufferlein T, Gress T, Schmid R, Büchler MW - BMC Cancer (2009)

Treatment scheme.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2696468&req=5

Figure 1: Treatment scheme.
Mentions: After implantation of a Port-A-Cath catheter patients will be treated as follows (see figure 1): All arms: 200 mg/m2/day 5-FU by continuous intravenous infusion on days 1–38; 64–101, and 120–161; three million units IFN-α2b subcutaneous three times weekly days 1–38 plus one injection prior to treatment start given during week -1 (approx. day -6). Non-steroidal anti-inflammatory drugs and steroids should be avoided if possible during IFN-α2b treatment. Only arm A and B: Beside 5–FU and IFN-α2b patients will be treated with external beam radiation: The pancreatic bed will be covered with a minimum margin of 2 cm. The porta hepatis, origins of the celiac axis and superior mesenteric artery will be included. The fields must include the entire duodenal C-loop as seen on pre-operative CT scan. Total dose will be 50.4 Gy in 28 fractions over 5.5 weeks (1.8 Gy/day). Simulation should be done with the patient in the supine position with "arms up" position. A treatment planning CT is required to allow 3-D conformal treatment planning. Conventional 3-D treatment techniques as well as intensity modulated radiotherapy (IMRT) could be used for radiotherapy. At least a four field technique for 3-D planning or a multi-field technique for IMRT is necessary. Furthermore a multi-leaf collimator is required to allow customized blocking and IMRT. Equipment: greater than or equal to 6 MeV photons should be used. Only study arm A): Cisplatin 30 mg/m2 IV over 60 minutes on days 1, 8, 15, 22, 29, 36 (6 doses). Two to three hours before and after Cisplatin dose the patients will receive hydration of at least 2 litres. Patients will be taught to drink at least 1 litre during the day.

Bottom Line: First clinical results are expected for the end of 2009.Primary endpoint is the comparison of the treatment groups with respect to six-month event-free-survival.An event is defined as grade 3 or grade 4 toxicity, objective tumour recurrence, or death.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg 69120, Germany. angela.maerten@med.uni-heidelberg.de

ABSTRACT

Background: The 5-year survival of patients with resected pancreatic adenocarcinoma is still unsatisfying. The ESPAC-1 and the CONKO 001 trial proofed that adjuvant chemotherapy improves 5-year survival significantly from approximately 14% to 21%. In parallel, investigators from the Virginia Mason Clinic reported a 5-year survival rate of 55% in a phase II trial evaluating a combination of adjuvant chemotherapy, immunotherapy and external beam radiation (CapRI-scheme). Two other groups confirmed in phase II trials these results to a certain extent. However, these groups reported severe gastrointestinal toxicity (up to 93% grade 3 or 4 toxicity). In a randomized controlled phase III trial, called CapRI, 110 patients were enrolled from 2004 to 2007 in Germany and Italy to check for reproducibility. Interestingly, much less gastrointestinal toxicity was observed. However, dose-reduction due to haematological side effects had to be performed in nearly all patients. First clinical results are expected for the end of 2009.

Methods/design: CapRI-2 is an open, controlled, prospective, randomized, multicentre phase II trial with three parallel arms. A de-escalation of the CapRI-scheme will be tested in two different modifications. Patients in study arm A will be treated as outpatients with the complete CapRI-scheme consisting of cisplatin, Interferon alpha-2b and external beam radiation and three cycles of 5-fluorouracil continuous infusion. In study arm B the first de-escalation will be realised by omitting cisplatin. Next, patients in study arm C will additionally not receive external beam radiation. A total of 135 patients with pathologically confirmed R0 or R1 resected pancreatic adenocarcinoma are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to six-month event-free-survival. An event is defined as grade 3 or grade 4 toxicity, objective tumour recurrence, or death.

Discussion: The aim of this clinical trial is to evaluate de-escalation of the CapRI-scheme. It is hypothesised that removal of cisplatin and radiotherapy will have no significant effect or only a minor impact on the clinical response but result in substantially lower toxicity.

Trial registration: Current Controlled Trials ISRCTN79802092.

Show MeSH
Related in: MedlinePlus