Locally Advanced Pancreatic AdenocarcinomaPhase 3CIPHERNCT03536182
Trial of Carbon Ion Versus Photon Radiotherapy for Locally Advanced, Unresectable Pancreatic Cancer
A Phase 3 study testing Carbon Ion Radiation Therapy (CIRT) and Intensity Modulated Radiation Therapy (IMRT) in people with Locally Advanced Pancreatic Adenocarcinoma, run by University of Texas Southwestern Medical Center at 2 sites in 2 countries.
Trial summary
To determine if carbon ion radiotherapy improves overall survival versus photon therapy in patients with locally advanced, unresectable pancreatic cancer Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Locally Advanced Pancreatic Adenocarcinoma
- What is being tested?
- Carbon Ion Radiation Therapy (CIRT) and Intensity Modulated Radiation Therapy (IMRT)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 29 May 2019to 1 Jul 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients must be willing and capable to provide informed consent within the 30 days prior to registration to participate in the protocol.
- Histological and/or cytological diagnosis of pancreas adenocarcinoma must be done at any point prior to registration
- Unresectable by radiographic or exploration within 30 days of registration
- Age ≥ 18 years.
- Distance from the pancreas tumor edge to the bowel and stomach > 3 mm (in both the prone and supine positions)
- Tumor does not exceed 15 cm in greatest dimension
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- 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.
- Zubrod performance status of 0-1, within 30 days prior to registration.
- 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)
- Patients must complete all required pretreatment evaluations
- Able to travel to a foreign country within approximately 4 weeks of randomization (for patients enrolled outside of Japan and Italy)
- 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.
- 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).
Who cannot join
- Subjects receiving other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or nab-paclitaxel or other agents used in study.
- Subjects who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
- Prior radiation to the upper abdomen
- Placement of a metal stent for relief of biliary obstruction (metal stents may be placed following completion of radiation therapy).
- Body weight >100 kg
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- Active inflammatory bowel disease or active gastric/duodenal ulcer
- Metal implants in the upper abdomen
- Expected medical intolerance of radiotherapy, concurrent chemotherapy, and/or adjuvant chemotherapy.
- History of HIV or hepatitis B or C
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Japan1 site
National Institute of Radiological Sciences,4-9-1, Anagawa, Inage-ku,
Chiba, 263-8555
About this study
Official title: CIPHER: A Prospective, Multi-Center Randomized Phase 3 Trial of Carbon Ion Versus Conventional Radiation Therapy for Locally Advanced, Unresectable Pancreatic Cancer
To determine if carbon ion radiotherapy improves overall survival versus photon therapy in patients with locally advanced, unresectable pancreatic cancer
Read the detailed 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:
- Definitive treatment :
- Neoadjuvant treatment:
Adjuvant chemotherapy 4 cycles of gemcitabine/nab-paclitaxel or FOLFIRNOX, Gemcitabine alone if these regimens are unavailable
- Being tested
- Carbon Ion Radiation Therapy (CIRT), Intensity Modulated Radiation Therapy (IMRT)
- Keywords
- Pancreas, Adenocarcinoma.
- Medical subject headings
- Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carbon Ion Radiation Therapy (CIRT)Radiation
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)Radiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Carbon ion radiotherapy | Active comparator | The dose calculation algorithms used in Japan and Europe (local effect model, LEM) are different, so the total dose must be modified to ensure consistency
1. Japan : 55.2 GyE in 4.6 GyE per fraction in 12 fractions delivered 4 days a week. At least 90% of each CTV receives at least 95% of the prescribed dose, and 100% of the GTV V95 must receive at least 95% of the prescribed dose.
2. European: . Patients treated in Europe should receive 57.6 GyE in 4.8 GyE per fraction in 12 fractions delivered 4 days a week. At least 90% of CTV receives at least 95% of the prescribed dose, and 100% of the GTV V95 must receive at least 95% of the prescribed dose. This evaluation will occur in the LEM system Receives: Radiation: Carbon Ion Radiation Therapy (CIRT) |
| Arm B: Photon radiotherapy | Active comparator | 50.4-56 Gy in 1.8-2.0 Gy per fraction in 28 fractions delivered 5 days a week. The plan should be normalized such that 100% of the PTV receives at least 48.9 Gy (i.e. 97% of 50.4 Gy). In addition, 100% of the GTV should receive at least 50.4 Gy. The maximum dose allowed to a point volume (0.03 mL) is 115% of the prescribed dose. Receives: Radiation: Intensity Modulated Radiation Therapy (IMRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 Years
Secondary outcomes (4)
Progression-free survival
To compare progression-free survival between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma
Measured: 2 Years
Patterns-of-failure
To compare patterns-of-failure between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma
Measured: 2 years
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).
Measured: 12 Months
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2018
- Study start29 May 2019
- Primary completion1 Jul 2021 (estimated)
- Study completion1 Jul 2023 (estimated)
Why it stopped: Due to COVID and other recruitment issues the trial could not be initiated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Eligible patients will be randomized in a 2:1 fashion (carbon:photon) between carbon ion radiotherapy or intensity modulated radiation therapy. Assuming a 10% dropout risk, the study will have 82% power to detect an increase in 2-year survival from 22% to 48% with carbon ion radiotherapy.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Sher, University of Texas Southwestern Medical Center
- Investigators
- David Sher, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03536182
- Sponsor's protocol ID
- STU 022016-002
- Acronym
- CIPHER
- Status last verified
- May 2021
- First submitted
- 20 Apr 2018
- Last updated
- 26 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CIPHER: A Prospective, Multi-Center Randomized Phase 3 Trial of Carbon Ion Versus Conventional Radiation Therapy for Locally Advanced, Unresectable Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT03536182
- Acronym / sponsor ID
- CIPHER / STU 022016-002
- Keywords
- Pancreas, Adenocarcinoma.
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to COVID and other recruitment issues the trial could not be initiated.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 29 May 2019 (actual)
- Primary completion
- 1 Jul 2021 (estimated)
- Study completion
- 1 Jul 2023 (estimated)
- First posted
- 24 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine if carbon ion radiotherapy improves overall survival versus photon therapy in patients with locally advanced, unresectable pancreatic cancer
Detailed 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:
- Definitive treatment :
- Neoadjuvant treatment:
Adjuvant chemotherapy 4 cycles of gemcitabine/nab-paclitaxel or FOLFIRNOX, Gemcitabine alone if these regimens are unavailable
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Eligible patients will be randomized in a 2:1 fashion (carbon:photon) between carbon ion radiotherapy or intensity modulated radiation therapy. Assuming a 10% dropout risk, the study will have 82% power to detect an increase in 2-year survival from 22% to 48% with carbon ion radiotherapy.
| Arm | Type | Receives |
|---|---|---|
| Arm A: Carbon ion radiotherapy | Active comparator | Radiation: Carbon Ion Radiation Therapy (CIRT)The dose calculation algorithms used in Japan and Europe (local effect model, LEM) are different, so the total dose must be modified to ensure consistency 1. Japan : 55.2 GyE in 4.6 GyE per fraction in 12 fractions delivered 4 days a week. At least 90% of each CTV receives at least 95% of the prescribed dose, and 100% of the GTV V95 must receive at least 95% of the prescribed dose. 2. European: . Patients treated in Europe should receive 57.6 GyE in 4.8 GyE per fraction in 12 fractions delivered 4 days a week. At least 90% of CTV receives at least 95% of the prescribed dose, and 100% of the GTV V95 must receive at least 95% of the prescribed dose. This evaluation will occur in the LEM system |
| Arm B: Photon radiotherapy | Active comparator | Radiation: Intensity Modulated Radiation Therapy (IMRT)50.4-56 Gy in 1.8-2.0 Gy per fraction in 28 fractions delivered 5 days a week. The plan should be normalized such that 100% of the PTV receives at least 48.9 Gy (i.e. 97% of 50.4 Gy). In addition, 100% of the GTV should receive at least 50.4 Gy. The maximum dose allowed to a point volume (0.03 mL) is 115% of the prescribed dose. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- All patients must be willing and capable to provide informed consent within the 30 days prior to registration to participate in the protocol.
- Histological and/or cytological diagnosis of pancreas adenocarcinoma must be done at any point prior to registration
- Unresectable by radiographic or exploration within 30 days of registration
- Age ≥ 18 years.
- Distance from the pancreas tumor edge to the bowel and stomach > 3 mm (in both the prone and supine positions)
Key exclusion criteria (10 listed)
- Subjects receiving other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or nab-paclitaxel or other agents used in study.
- Subjects who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
- Prior radiation to the upper abdomen
- Placement of a metal stent for relief of biliary obstruction (metal stents may be placed following completion of radiation therapy).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Radiation | Arm A: Carbon ion radiotherapy |
| 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. | Radiation | Arm B: Photon radiotherapy |
Primary outcome
Over all Survival
Time frame: 2 Years
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.
4 secondary outcomes
Progression-free survival
Time frame: 2 Years
Patterns-of-failure
Time frame: 2 years
Quality-of-life Comparison
Time frame: 12 Months
Toxicity using CTCAE 5.0
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Sher, MD principal investigator
University of Texas Southwestern Medical Center
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Carbon Ion Radiation Therapy (CIRT) and Intensity Modulated Radiation Therapy (IMRT) in people with Locally Advanced Pancreatic Adenocarcinoma, run by University of Texas Southwestern Medical Center at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 26 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Over all Survival (time frame: 2 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2021.