Metastatic Pancreatic CancerPhase 1/2NabucCONCT02109341
Phase I/II Study to Evaluate Nab-paclitaxel in Substitution of CPT11 or Oxaliplatin in FOLFIRINOX Schedule as First Line Treatment in Metastatic Pancreatic Cancer
A Phase 1/2 study testing Paclitaxel bound albumine in people with Metastatic Pancreatic Cancer, run by Gruppo Oncologico Italiano di Ricerca Clinica at 8 sites in Italy.
Trial summary
At this moment, FOLFIRINOX is the best treatment for selected patients (pts) with metastatic pancreatic cancer (mPC). Investigator would like to evaluate the substitution of CPT11 or Oxaliplatin in FOLFIRINOX schedule with Nab-paclitaxel (Nab-p) [Nab-FOLFIRI and Nab-FOLFOX]. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metastatic Pancreatic Cancer
- What is being tested?
- Paclitaxel bound albumine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 8 sitesItaly
- Study dates
- Feb 2014to Jan 2016
- Phase
- Phase 1/2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- . Males or females ≥ 18 years old and ≤ 75 years old;
- Histological or cytological evidence of a diagnosis of pancreatic ductal adenocarcinoma;
- Written informed consent prior to any study-specific procedures; 4. Measurable metastatic disease, defined in according to RECIST Version 1.1 (Eisenhower et al. 2009), that had not previously been treated with CT for metastatic disease;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 ;
- Absence of previous abdominal radiotherapy on target lesions (except radiation therapy analgesic if it has not been performed on measurable targets);
- Absence of heart failure or angina or infarction within 12 months previous inclusion;
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- Have adequate organ function including:
- Hematologic: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L.
- Hepatic: Bilirubin ≤ 1.5 times upper limits of normal (ULN) (Pts may have endoscopic or radiologic stenting to treat biliary obstructions).
- Renal: Serum creatinine within normal limits ≤1.5 times ULN.
Who cannot join
- Age of 76 years or older;
- Endocrine or acinar pancreatic carcinoma;
- Previous radiotherapy for measurable lesions;
- Central nervous system metastasis;
- Other concomitant cancer or history of cancer outside a carcinoma in situ of the cervix or basal or squamous cell of the skin;
- Pts already included in another clinical trial with other experimental drugs;
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- Current active infection;
- Have serious pre-existing medical conditions or serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris, or a clinically significant history of cardiac disease or uncontrolled diabetes mellitus);
- Females who are pregnant or lactating;
- Unable to undergo medical test for geographical, social or psychological reason
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Italy8 sites
Ospedale Sacro cuore di Gesù - FATEBENEFRATELLI
Benevento, BN, 82100
Azienda Ospedaliera Istituti Ospedalieri di Cremona
Cremona, 26100
SC Oncologia Medica 1
Florence, FI, 50134
Ospedale S. Chiara - Azienda Ospedaliero-Universitaria Pisana
Pisa, 56126
Arcispedale Santa Maria Nuova
Reggio Emilia, 42100
Regina Elena National Cancer Institute
Rome, Rome, 00144
IRCCS Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, FG, 71013
Ospedale Borgo Roma
Verona, 37134
About this study
At this moment, FOLFIRINOX is the best treatment for selected patients (pts) with metastatic pancreatic cancer (mPC). Investigator would like to evaluate the substitution of CPT11 or Oxaliplatin in FOLFIRINOX schedule with Nab-paclitaxel (Nab-p) [Nab-FOLFIRI and Nab-FOLFOX].
Doses for Nab-FOLFIRI and Nab-FOLFOX will be determined by the phase I trial. One or both schedules will be evaluated in successive phase II part.
Read the detailed description
The primary objective for phase I of the study is to determine the MTD of Nab-p when used in substitution of OXA or CPT11 in FOLFIRINOX schedule, as first-line treatment in pts with mPC. The dose finding strategy will be based on the classical 3+3 dose escalation design.
-Analysis sets: Modified intention-to-treat population: it consists of all pts who are allocated and receive at least one dose of any component of study treatment. Pts will be grouped according to the randomized treatment assignment. Pts treated during the phase I step will be not included in this population.
Safety population: it consists of all pts who are allocated and receive at least one dose of any component of study treatment. Groups are defined by the study treatment actually received. Pts treated at the MTD during the phase I step will be not included in this population.
Statistical methods Best ORR will be summarized and 95% confidence limits will be calculated according to the exact method for each of the treatment arms included in the phase II step.
All the analyses of primary and secondary efficacy variables will be performed on the modified intention-to-treat population.
The overall incidences of AEs will be summarized. Pts who experienced the same event on more than one occasion are counted only once in the calculation of the event frequency, at the highest intensity ever observed.
Serious adverse events will be summarized. All the safety analyses will be performed on the safety population.
-Sample size: The experimental treatment, to be considered clinically worthwhile, should determine an overall best RR equal to or greater than 40%. According to the Fleming single stage design, for a 90% power towards an alternative hypothesis of an ORR equal to or greater than 40% and a one-sided type I error rate of 5%, respect to the null hypothesis of an ORR equal to or less than 20%, 42 pts must be included in the final evaluation, in each arm of the phase II step. According to the exact binomial test, the experimental treatment will be considered sufficiently promising and candidate to further studies in the case of a major objective response is seen in at least 14 pts.
- Conditions
- Metastatic Pancreatic Cancer
- Being tested
- Paclitaxel bound albumine
- Keywords
- mPC
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paclitaxel bound albumineDrug
Also called nab-paclitaxel
| Study group | Role | What they receive |
|---|---|---|
| Nab-FOLFIRI | Experimental | In the phase I study, all pts enrolled in this arm will receive Nab-FOLFIRI: Irinotecan, 180 mg per square meter of body surface area (m2 ) + Leucovorin, 400 mg/m2 and 5-Fluorouracil, 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion, plus Nab-p per cohort escalation assignment starting with 90 mg/m2 every 2 weeks. Pts continued treatment until a total of 12 administrations, disease progression or unacceptable toxicity.
Pts enrolled in arm A for phase II will receive the dose of Nab-FOLFIRI as determined in the Phase I and in the same sequence. Receives: Drug: Paclitaxel bound albumine |
| Nab-FOLFOX | Experimental | In the phase I study, all pts enrolled in this arm will receive Nab-FOLFOX: Oxaliplatin 85 mg/m2 +Leucovorin, 400 mg/m2 and 5-Fluorouracil, 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion, plus Nab-p per cohort escalation assignment starting with 90 mg/m2, every 2 weeks.
Pts continued treatment until a total of 12 administrations, disease progression or unacceptable toxicity.
Pts enrolled in arm B for phase II will receive the dose of Nab-FOLFOX as determined in the Phase I and in the same sequence Receives: Drug: Paclitaxel bound albumine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose finding safety and activity
To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the combination Nab-paclitaxel+ Irinotecan+ Leucovorin+ 5-Fluorouracil (Nab-FOLFIRI) and of the combination Nab-paclitaxel+ Oxaliplatin+ Leucovorin+ 5-Fluorouracil (Nab- FOLFOX) in pts with mPC in first-line chemotherapy (CT).
To assess efficacy of Nab-FOLFIRI and Nab-FOLFOX in pts with mPC in first-line CT , in term of ORR [Complete response (CR) + partial responses (PR)].
Measured: 18 months
Secondary outcomes (5)
Clinical benefit rate [CR+PR+ stable diseases (SD)]
- Clinical benefit rate [CR+PR+ stable diseases (SD)]: this is defined as the occurrence of either a confirmed CR or PR objective response or a SD over the entire course of treatment, as determined by the RECIST 1.1 criteria based on investigator assessment. Pts for whom no records of post-baseline tumor assessments are reported will be counted as non-responders
Measured: 18 months
Progression free survival (PFS) for each schedule
- Duration of PFS: this is defined as the time between the date of randomization and the date of first evidence of progressive disease or date of death, whichever occurs first. Documentation of disease progression will be defined as per RECIST 1.1 criteria based on investigator assessment. The censoring date for a patient who is known to be progression-free would be the date of the last tumor assessment.
Measured: 18 months
Overall survival (OS),
- Duration of OS: is the time from the date of randomization to the date of death from any cause. For pts who are still alive on the date of clinical data cut-off for the OS analysis, the last date when the patient is known to be alive on or prior to the clinical cut-off date will be used to determine the censoring date. For pts who do not have any post-baseline information, data will be censored at the date of randomization plus one day.
Measured: 18 months
Quality of life (QoL) for each schedule
- QoL : assessment of quality of life with the use of the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life core questionnaire (QLQ-C30, version 3.0). The primary QoL endpoint will be the time to a definitive 5% deterioration in the global health status/QoL scale of the QLQ-C30 questionnaire.
Measured: 18 months
Safety profile
- Safety profile: Safety of the treatment will be evaluated by serious and non serious adverse events (AEs). AEs will be graded according to the CTCAE v4.03
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2014 (estimated)
- Study startFeb 2014
- Primary completionDec 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Pancreatic CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gruppo Oncologico Italiano di Ricerca Clinica
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Francesco Di Costanzo, MD, Principal investigator, AOU CareggiElisa Giommoni, MD, Principal investigator, Gruppo Oncologico Italiano di Ricerca Clinica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02109341
- Sponsor's protocol ID
- Goirc 01-2013
- Other IDs
- 2013-002275-18
- Acronym
- NabucCO
- Status last verified
- Feb 2017
- First submitted
- 2 Apr 2014
- Last updated
- 3 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study to Evaluate Nab-paclitaxel in Substitution of CPT11 or Oxaliplatin in FOLFIRINOX Schedule as First Line Treatment in Metastatic Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT02109341
- Acronym / sponsor ID
- NabucCO / Goirc 01-2013
- Conditions
- Metastatic Pancreatic Cancer
- Keywords
- mPC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- Gruppo Oncologico Italiano di Ricerca ClinicaUniversity, hospital or other
- Study start
- Feb 2014 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 9 Apr 2014 (estimated)
- 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.
At this moment, FOLFIRINOX is the best treatment for selected patients (pts) with metastatic pancreatic cancer (mPC). Investigator would like to evaluate the substitution of CPT11 or Oxaliplatin in FOLFIRINOX schedule with Nab-paclitaxel (Nab-p) [Nab-FOLFIRI and Nab-FOLFOX].
Doses for Nab-FOLFIRI and Nab-FOLFOX will be determined by the phase I trial. One or both schedules will be evaluated in successive phase II part.
Detailed description
The primary objective for phase I of the study is to determine the MTD of Nab-p when used in substitution of OXA or CPT11 in FOLFIRINOX schedule, as first-line treatment in pts with mPC. The dose finding strategy will be based on the classical 3+3 dose escalation design.
-Analysis sets: Modified intention-to-treat population: it consists of all pts who are allocated and receive at least one dose of any component of study treatment. Pts will be grouped according to the randomized treatment assignment. Pts treated during the phase I step will be not included in this population.
Safety population: it consists of all pts who are allocated and receive at least one dose of any component of study treatment. Groups are defined by the study treatment actually received. Pts treated at the MTD during the phase I step will be not included in this population.
Statistical methods Best ORR will be summarized and 95% confidence limits will be calculated according to the exact method for each of the treatment arms included in the phase II step.
All the analyses of primary and secondary efficacy variables will be performed on the modified intention-to-treat population.
The overall incidences of AEs will be summarized. Pts who experienced the same event on more than one occasion are counted only once in the calculation of the event frequency, at the highest intensity ever observed.
Serious adverse events will be summarized. All the safety analyses will be performed on the safety population.
-Sample size: The experimental treatment, to be considered clinically worthwhile, should determine an overall best RR equal to or greater than 40%. According to the Fleming single stage design, for a 90% power towards an alternative hypothesis of an ORR equal to or greater than 40% and a one-sided type I error rate of 5%, respect to the null hypothesis of an ORR equal to or less than 20%, 42 pts must be included in the final evaluation, in each arm of the phase II step. According to the exact binomial test, the experimental treatment will be considered sufficiently promising and candidate to further studies in the case of a major objective response is seen in at least 14 pts.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nab-FOLFIRI | Experimental | Drug: Paclitaxel bound albumineIn the phase I study, all pts enrolled in this arm will receive Nab-FOLFIRI: Irinotecan, 180 mg per square meter of body surface area (m2 ) + Leucovorin, 400 mg/m2 and 5-Fluorouracil, 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion, plus Nab-p per cohort escalation assignment starting with 90 mg/m2 every 2 weeks. Pts continued treatment until a total of 12 administrations, disease progression or unacceptable toxicity. Pts enrolled in arm A for phase II will receive the dose of Nab-FOLFIRI as determined in the Phase I and in the same sequence. |
| Nab-FOLFOX | Experimental | Drug: Paclitaxel bound albumineIn the phase I study, all pts enrolled in this arm will receive Nab-FOLFOX: Oxaliplatin 85 mg/m2 +Leucovorin, 400 mg/m2 and 5-Fluorouracil, 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion, plus Nab-p per cohort escalation assignment starting with 90 mg/m2, every 2 weeks. Pts continued treatment until a total of 12 administrations, disease progression or unacceptable toxicity. Pts enrolled in arm B for phase II will receive the dose of Nab-FOLFOX as determined in the Phase I and in the same sequence |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- . Males or females ≥ 18 years old and ≤ 75 years old;
- Histological or cytological evidence of a diagnosis of pancreatic ductal adenocarcinoma;
- Written informed consent prior to any study-specific procedures; 4. Measurable metastatic disease, defined in according to RECIST Version 1.1 (Eisenhower et al. 2009), that had not previously been treated with CT for metastatic disease;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 ;
- Absence of previous abdominal radiotherapy on target lesions (except radiation therapy analgesic if it has not been performed on measurable targets);
Key exclusion criteria (11 listed)
- Age of 76 years or older;
- Endocrine or acinar pancreatic carcinoma;
- Previous radiotherapy for measurable lesions;
- Central nervous system metastasis;
- Other concomitant cancer or history of cancer outside a carcinoma in situ of the cervix or basal or squamous cell of the skin;
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 |
|---|---|---|
| Paclitaxel bound albumineAlso: nab-paclitaxel | Drug | Nab-FOLFIRI, Nab-FOLFOX |
Primary outcome
Dose finding safety and activity
Time frame: 18 months
To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the combination Nab-paclitaxel+ Irinotecan+ Leucovorin+ 5-Fluorouracil (Nab-FOLFIRI) and of the combination Nab-paclitaxel+ Oxaliplatin+ Leucovorin+ 5-Fluorouracil (Nab- FOLFOX) in pts with mPC in first-line chemotherapy (CT). To assess efficacy of Nab-FOLFIRI and Nab-FOLFOX in pts with mPC in first-line CT , in term of ORR [Complete response (CR) + partial responses (PR)].
5 secondary outcomes
Clinical benefit rate [CR+PR+ stable diseases (SD)]
Time frame: 18 months
Progression free survival (PFS) for each schedule
Time frame: 18 months
Overall survival (OS),
Time frame: 18 months
Quality of life (QoL) for each schedule
Time frame: 18 months
Safety profile
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2017.
- Goirc Web siteLink provided by the sponsor.
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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.
Francesco Di Costanzo, MD principal investigator
AOU Careggi
Elisa Giommoni, MD principal investigator
Gruppo Oncologico Italiano di Ricerca Clinica
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Paclitaxel bound albumine in people with Metastatic Pancreatic Cancer, run by Gruppo Oncologico Italiano di Ricerca Clinica at 8 sites in Italy.
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 10 inclusion and 11 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: finished, as of the sponsor's last update on 3 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Italy. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Dose finding safety and activity (time frame: 18 months). 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 3 Feb 2017.