Trial of Carbon Ion Versus Photon Radiotherapy for Locally Advanced, Unresectable Pancreatic Cancer

Locally Advanced Pancreatic Adenocarcinoma Clinical Trial

— CIPHER  

Official title:

CIPHER: A Prospective, Multi-Center Randomized Phase 3 Trial of Carbon Ion Versus Conventional Radiation Therapy for Locally Advanced, Unresectable Pancreatic Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03536182
• Other study ID #: STU 022016-002
• Status: Withdrawn
• Phase: Phase 3
• Start date: May 29, 2019
• Est. completion date: July 1, 2023

Study information

• Verified date: May 2021
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine if carbon ion radiotherapy improves overall survival versus photon therapy in patients with locally advanced, unresectable pancreatic cancer

Description:

To compare the efficacy of carbon ion-based chemo radiotherapy with x-ray-based chemo radiotherapy for the treatment of locally advanced pancreatic adenocarcinoma by comparison of overall survival at 2 years following treatment. Patient has 2 in 3 chance of receiving Arm A and 1 in 3 chance of receiving Arm B. Arm A (chemoradiation takes place in Japan): CIRT in 12 fractions/treatments plus concurrent gemcitabine, followed by 4 cycles of gemcitabine + nab-Paclitaxel, or until progression or intolerance of therapy Arm B: IMRT in 28 fractions plus concurrent gemcitabine or capecitabine, followed by 4 cycles of gemcitabine + nab-Paclitaxel, or until progression or intolerance of therapy Per investigator discretion, patients may receive either: 1. Definitive treatment : 2. Neoadjuvant treatment: Adjuvant chemotherapy 4 cycles of gemcitabine/nab-paclitaxel or FOLFIRNOX, Gemcitabine alone if these regimens are unavailable

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 1, 2023
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

Inclusion Criteria:

1. All patients must be willing and capable to provide informed consent within the 30 days prior to registration to participate in the protocol.

2. Histological and/or cytological diagnosis of pancreas adenocarcinoma must be done at any point prior to registration

3. Unresectable by radiographic or exploration within 30 days of registration

4. Age = 18 years.

5. Distance from the pancreas tumor edge to the bowel and stomach > 3 mm (in both the prone and supine positions)

6. Tumor does not exceed 15 cm in greatest dimension

7. No evidence for metastatic disease as assessed by CT imaging of the chest, abdomen and pelvis OR by PET-CT within the 30 days prior to registration. Pancreas-protocol CT or magnetic resonance imaging (MRI) with gadolinium (for patients who cannot receive CT contrast) is required as part of this evaluation.

8. Zubrod performance status of 0-1, within 30 days prior to registration.

9. Adequate hematologic, renal, and liver function as defined by:Adequate hematologic, renal, and liver function as defined by: Absolute neutrophil count > 1500 cells/mm3 Creatinine <1.5 mg/dL Hemoglobin = 8.0 g/dL AST and ALT < 2.5 X ULN Bilirubin = 1.5 times the ULN (after stent placement, if necessary)

10. Patients must complete all required pretreatment evaluations

11. Able to travel to a foreign country within approximately 4 weeks of randomization (for patients enrolled outside of Japan and Italy)

12. If a patient receives 1 or 2 cycles of chemotherapy at an outside facility, pre-treatment laboratory values must meet the above criteria. If the protocol-compliant imaging had not been obtained prior to chemotherapy, they may be performed prior to registration and any additional chemotherapy being infused.

13. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following

criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

Exclusion Criteria:

1. Subjects receiving other investigational agents.

2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or nab-paclitaxel or other agents used in study.

3. Subjects who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

4. Prior radiation to the upper abdomen

5. Placement of a metal stent for relief of biliary obstruction (metal stents may be placed following completion of radiation therapy).

6. Body weight >100 kg

7. Active inflammatory bowel disease or active gastric/duodenal ulcer

8. Metal implants in the upper abdomen

9. Expected medical intolerance of radiotherapy, concurrent chemotherapy, and/or adjuvant chemotherapy.

10. History of HIV or hepatitis B or C

Related Conditions & MeSH terms

• Adenocarcinoma
• Locally Advanced Pancreatic Adenocarcinoma

Intervention

Radiation:
• Carbon Ion Radiation Therapy (CIRT)
Patient will receive CIRT daily, 4 days a week for a total of 12 fractions/treatments plus concurrent chemotherapy (gemcitabine) weekly for 3 weeks. Gemcitabine will be given intravenously over about 1 hour in the outpatient clinic. Within 6 weeks of completing radiotherapy, patient will start 4 cycles of chemotherapy. If the doctor chooses gemcitabine+nab-Paclitaxel, patient will receive gemcitabine and nab-paclitaxel intravenously once a week for 3 weeks then 1 week off, for a total of 4 cycles (16 weeks). If the doctor chooses FOLFIRINOX, then patient will receive oxaliplatin, irinotecan, infusional 5-fluorouracil, and possibly leucovorin, all intravenously, every 2 weeks, for a total of 16 weeks.
• Intensity Modulated Radiation Therapy (IMRT)
Patient will receive IMRT daily, 5 days a week for a total of 28 fractions/treatments plus concurrent chemotherapy (gemcitabine or capecitabine) weekly for 5 weeks. Gemcitabine will be given intravenously over about 1 hour in the outpatient clinic,within 6 weeks of completing radiotherapy,patient will start 4 cycles of chemotherapy. If the doctor chooses gemcitabine+nab-Paclitaxel, patient will receive gemcitabine and nab-paclitaxel intravenously once a week for 3 weeks then 1 week off, for a total of 4 cycles (16 weeks). If the doctor chooses FOLFIRINOX, then patient will receive oxaliplatin, irinotecan, infusional 5-fluorouracil, and possibly leucovorin, all intravenously, every 2 weeks, for a total of 16 weeks.

Locations

Country	Name	City	State
Japan	National Institute of Radiological Sciences,4-9-1, Anagawa, Inage-ku,	Chiba
United States	University of Texas Southwestern Medical Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Over all Survival	To compare the efficacy of carbon ion-based chemoradiotherapy with x-ray-based chemoradiotherapy for the treatment of locally advanced pancreatic adenocarcinoma by comparison of overall survival following treatment.	2 Years
Secondary	Progression-free survival	To compare progression-free survival between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma	2 Years
Secondary	Patterns-of-failure	To compare patterns-of-failure between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma	2 years
Secondary	Quality-of-life Comparison	To compare quality-of-life and toxicity outcomes between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma.The quality-of-life assessment will be performed during and after treatment. Patient-reported functional status will be assessed with the hepatobiliary subscales of the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep).	12 Months
Secondary	Toxicity using CTCAE 5.0	Only adverse events assessed to be definitely, probably, or possibly related to protocol treatment will be considered. The rates of all Grade 3-5 adverse events, and death during or within 30 days of discontinuation of protocol treatment using CTCAE 5.0.	2 years