Metastatic Pancreas AdenocarcinomaPhase 1FABLOxNCT02620800
Study of 5-fluorouracil (5-FU), Nab®1-paclitaxel, Bevacizumab, Leucovorin, and Oxaliplatin in Patients With Metastatic Pancreatic Cancer
A Phase 1 study testing 5FU, nab-paclitaxel and bevacizumab in people with Metastatic Pancreas Adenocarcinoma, run by Celgene at 7 sites in United States.
Trial summary
The purpose of this study is to learn about the safety and potential benefit of metronomic 5-fluorouracil in combination with nab®1-paclitaxel, bevacizumab, leucovorin, and oxaliplatin in treating patients with metastatic pancreatic adenocarcinoma. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Metastatic Pancreas Adenocarcinoma
- What is being tested?
- 5FU, nab-paclitaxel and bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 7 sitesUnited States
- Study dates
- 18 Jan 2016to 29 Oct 2018
- Phase
- Phase 1
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A subject will be eligible for inclusion in this study only if all of the following criteria are met:
- Male or female subject is between 18 and 65 years of age at the time of signing the Informed Consent Form (ICF).
- Subject has definitive histologically or cytologically confirmed metastatic pancreatic adenocarcinoma.
- Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
- Subject has one or more tumors measurable by CT scan (or (MRI), if allergic to CT contrast media) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
- Subject has the following blood counts / Hemoglobin (Hgb) at screening:
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- Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L;
- Platelet count ≥ 100,000/mm3 (100 × 10^9/L);
- Hgb ≥ LLN or 10 g/dL.
- Subject has the following blood chemistry levels at screening:
- AST (SGOT), ALT (SGPT) ≤ 2.5 x upper limit of normal range (ULN); if hepatic metastases present ≤ 5.0 x ULN
- Total bilirubin ≤ 1.5 X ULN
- Creatinine clearance ≥ 60 mL/min (by Cockroft-Gault)
- Albumin ≥ 3.5 grams/dL7.
- Females of childbearing potential (FOCBP) [defined as a sexually mature woman who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 consecutive months)] must:
- Have a negative pregnancy test (β-human chorionic gonadotropin [β -hCG]) as verified by the study doctor within 72 hours prior to starting study therapy
- Commit to complete abstinence from heterosexual contact, or agree to use medical doctor-approved contraception throughout the study without interruption; while receiving study medication and for at least 6 months following last dose of study IP.
- Males must practice complete abstinence or agree to use a condom (even if he has undergone a successful vasectomy) during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 6 months following last dose of study IP.
- Subject has no clinically significant abnormalities in urinalysis results at baseline.
- Subject is able to adhere to the study visit schedule and other protocol requirements.
- Subject understands the nature of the study, and has agreed to participate in the study, and has voluntarily signed the ICF prior to participation in any study-related activities.
- Subject must consent to provide protocol-mandated tumor and blood samples for molecular analysis.
- Subject is willing and able to adhere to the study visit schedule and other protocol requirements
Who cannot join
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- Subject has received previous systemic chemotherapy or investigational therapy (other than that as a radiosensitizer concomitant with radiotherapy) for the treatment of pancreatic adenocarcinoma, including neo-adjuvant or adjuvant therapy.
- Subject has known brain metastases unless previously treated and controlled for a minimum of 2 weeks prior to enrollment. Subject is not receiving corticosteroids with no evidence of cerebral edema.
- Pre-existing peripheral neuropathy > Grade 1
- Subject with unstable stent.
- History of malignancy in the last 3 years. Subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 3 years.
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- Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy , defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.
- Subject has known historical or active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C or subject receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the Investigator, increase the risk of serious neutropenic complications.
- Subject has undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study or surgical wound has not fully healed.
- Subject has a history of allergy or hypersensitivity to any of the IP or any of their excipients, or the subject exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections for and of the products' Summary of Product Characteristics or Prescribing Information.
- History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).
- Subject with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies that in the opinion of the Investigator may put them at increased risk of interstitial pneumonitis.
- Subject with high cardiovascular risk, including, but not limited to:
- uncontrolled hypertension
- unstable angina
- diagnosis of ischemic heart disease
- heart disease of New York Heart Association functional classification ≥ 3 (see Appendix C)
- prior history of hemorrhagic or thrombolytic stroke
- prior exposure to anthracycline
- history of peripheral artery disease (eg, claudication, Leo Buerger's disease)
- any of the following within the prior 6 months
- coronary stenting
- myocardial infarction
- coronary bypass surgery
- Recent history of clinically significant hemoptysis.
- Pregnant and nursing (lactating) women.
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Subject has any condition that confounds the ability to interpret data from the study.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Michigan
Ann Arbor, Michigan, 48103
Tufts - New England Medical Center
Boston, Massachusetts, 02111
Northwestern University
Chicago, Illinois, 60611
Karmanos Cancer Center Wayne State University
Detroit, Michigan, 48201
Cornell University Weill Medical College
New York, New York, 10065
Virginia Mason Cancer Center
Seattle, Washington, 98101
Gibbs Cancer Center and Research Institute
Spartanburg, South Carolina, 29303
About this study
Official title: An Open Label, Multicenter, Single Arm, Phase 1/2 Trial of Metronomic 5-fluorouracil in Combination With Nab-paclitaxel, Bevacizumab, Leucovorin, and Oxaliplatin in Patients With Metastatic Pancreatic Adenocarcinoma.
The purpose of this study is to learn about the safety and potential benefit of metronomic 5-fluorouracil in combination with nab®1-paclitaxel, bevacizumab, leucovorin, and oxaliplatin in treating patients with metastatic pancreatic adenocarcinoma.
Read the detailed description
The Phase 1 portion of the study is an open-label study enrolling subjects with metastatic pancreatic adenocarcinoma who have not previously received systemic chemotherapy at any time as treatment for pancreatic cancer (including adjuvant chemotherapy), except low dose chemotherapy administered as a radiosensitizer concomitant with radiotherapy and to determine the recommended Phase 2 dose (RP2D) and dose-limiting toxicities (DLTs) of metronomic 5-FU in combination with nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma.
Subjects will be enrolled in cohorts of 6 subjects. There will be no dose escalation. Dose limiting toxicities will be assessed in cycle 1. If there is an incidence of ≥2 of 6 subjects experiencing a DLT, the dose will be de-escalated to the next lower dose. Based on the totality of the data, the investigators may advise the Sponsor to evaluate additional subjects at any of the dose levels. Upon Sponsor agreement, if additional subjects are enrolled at any dose level, DLT evaluation will occur at that same ratio (if ≥ 4 of 12 subjects, or ≥ 6 of 18 subjects experience a DLT, the dose will be de-escalated). Approximately 12-24 subjects will be enrolled in the Phase 1 portion of the study, dependent on the number of dose levels examined and the number of subjects enrolled at each dose level.
Safety will continuously be evaluated by incidence of Treatment Emergent Adverse Events (TEAEs) by the Medical Dictionary for Drug Regulatory Activities (MedDRA) and severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 (v4.03).
The Phase 2 part of the study is to determine if the combination of metronomic 5-FU, nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin at the RP2D defined in Phase 1 achieves a clinically meaningful improvement in 1 year survival rate over the historical control. Approximately 60 subjects are planned to be enrolled in the Phase 2 portion of the study.
Subjects may remain on treatment until disease progression, unacceptable toxicity, withdrawal of consent, physician decision, or death. The anticipated duration of the study (including Phase 1, Phase 2 and follow-up) is approximately 4 years.
The Phase 1 portion of the study is an open-label study enrolling subjects with metastatic pancreatic adenocarcinoma who have not previously received systemic chemotherapy at any time as treatment for pancreatic cancer (including adjuvant chemotherapy), except low dose chemotherapy administered as a radiosensitizer concomitant with radiotherapy and to determine the recommended Phase 2 dose (RP2D) and dose-limiting toxicities (DLTs) of metronomic 5-FU in combination with nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma.
Subjects will be enrolled in cohorts of 6 subjects. There will be no dose escalation. Dose limiting toxicities will be assessed in cycle 1. If there is an incidence of ≥2 of 6 subjects experiencing a DLT, the dose will be de-escalated to the next lower dose. Based on the totality of the data, the investigators may advise the Sponsor to evaluate additional subjects at any of the dose levels. Upon Sponsor agreement, if additional subjects are enrolled at any dose level, DLT evaluation will occur at that same ratio (if ≥ 4 of 12 subjects, or ≥ 6 of 18 subjects experience a DLT, the dose will be de-escalated). Approximately 12-24 subjects will be enrolled in the Phase 1 portion of the study, dependent on the number of dose levels examined and the number of subjects enrolled at each dose level.
Safety will continuously be evaluated by incidence of Treatment Emergent Adverse Events (TEAEs) by the Medical Dictionary for Drug Regulatory Activities (MedDRA) and severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 (v4.03).
The Phase 2 part of the study is to determine if the combination of metronomic 5-FU, nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin at the RP2D defined in Phase 1 achieves a clinically meaningful improvement in 1 year survival rate over the historical control. Approximately 60 subjects are planned to be enrolled in the Phase 2 portion of the study.
Subjects may remain on treatment until disease progression, unacceptable toxicity, withdrawal of consent, physician decision, or death. The anticipated duration of the study (including Phase 1, Phase 2 and follow-up) is approximately 4 years.
Upon completion of the Phase 1 portion of the study, a decision not to proceed with the Phase 2 portion was taken by the Sponsor. The decision to terminate the study after Phase 1 was not based on any safety concerns that posed an unacceptable risk for this patient population and no safety issues have been identified.
- Conditions
- Metastatic Pancreas Adenocarcinoma
- Being tested
- 5FU, nab-paclitaxel, bevacizumab, calcium leucovorin, oxaliplatin
- Keywords
- Metastatic Pancreatic Cancer, Adenocarcinoma, Open-label, Phase 1/2, Metronomic, Chemotherapy, ABI-007, nab-paclitaxel, Abraxane, gemcitabine, Gemzar, bevacizumab, Avastin, 5-Fluorouracil (5-FU), leucovorin, oxaliplatin, Eloxatin
- Medical subject headings
- Pancreatic Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5FUDrug
5 fluorouracil (5-FU) (180 mg/m^2/day for 14 days) by CIVI via ambulatory pump
nab-paclitaxelDrug
Also called Abraxane, ABI-007
nab-paclitaxel (75 mg/m^2) as a 30-minute (min) IV infusion on Days 1, 8, and 15
bevacizumabDrug
Also called Avastin
bevacizumab (5 mg/kg) as an IV infusion on Days 1 and 15
calcium leucovorinDrug
Also called Citrovorum Factor, Folinic Acid
calcium leucovorin (20 mg/m^2) IV bolus, on Days 1, 8, 15
oxaliplatinDrug
Also called Elotaxin
oxaliplatin (40 mg/m^2) as a 60-min IV infusion on Days 1, 8, and 15
| Study group | Role | What they receive |
|---|---|---|
| FABLOx | Experimental | 5 fluorouracil (5-FU ) (180 mg/m^2/day for 14 days), by continuous intravenous infusion (CIVI) via ambulatory pump, nab-paclitaxel (75 mg/m^2) as a 30-minute (min) IV infusion on Days 1, 8, and 15, bevacizumab (5 mg/kg) as an IV infusion on Days 1 and 15, calcium leucovorin (20 mg/m^2) IV bolus on Days 1, 8, 15, and oxaliplatin (40 mg/m^2) as a 60-min IV infusion on Days 1, 8, and 15. First bevacizumab infusion is given over 90 minutes. Receives: Drug: 5FU; Drug: nab-paclitaxel; Drug: bevacizumab; Drug: calcium leucovorin; Drug: oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities (Phase 1)
- Any toxicity starting during the first 28 days of treatment and requiring 14 days or more of treatment interruption • Grade 3 or 4 neutropenia associated with fever > 38.5°C • Grade 3 anemia requiring a transfusion • Any Grade 4 hematological toxicity lasting > 7 days • Grade 4 thrombocytopenia or a Grade 3 or 4 thrombocytopenia associated with clinically significant bleeding • Grade 3 or 4 non-hematological toxicity with the exception of fatigue, due to any of the study drugs and unresponsive to medical treatment within 4 days of onset • Subjects who experience Grade ≥ 3 hyperbilirubinemia as an apparent DLT. If a Phase 1 subject experiences a Grade ≥ 3 hyperbilirubinemia due principally to unconjugated bilirubin, it will not be defined as a DLT. The subject will be removed from the study and the Phase 1 subject will be replaced. • Any non-hematologic toxicity delaying the initiation of cycle 2 by > 21 days • Grade ≥ 2 pneumonitis or interstitial lung disease
Measured: Up to Day 1 of Cycle 2
1 year survival rate (Phase II portion)
1 year survival rate is defined as the time interval between the date of first dose of Investigational Product (IP) and the date of death.
Measured: Up to 1 year
Number of subjects experiencing Adverse Events (AEs) by severity and overall tabulations by cohort and overall including treatment emergent and Serious AEs
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. All AEs will be recorded by the Investigator from the time the subject signs informed consent until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to Investigational Product.
Measured: Up to 4 years
Secondary outcomes (7)
Summary for the number of subjects experiencing Adverse Events (AEs) by severity and overall in tabulations by cohort and overall including treatment emergent AEs and Serious AEs
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. All AEs will be recorded by the Investigator from the time the subject signs informed consent until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP
Measured: Up to 4 years
Objective Response Rate using Response Evaluation Criteria In Solid Tumours (Recist) v1.1 presented by frequency and percentages
Subjects with confirmed complete or partial response (CR and PR) will be presented by 95% Confidence Intervals (CIs) around the proportion of (CR+PR)/N where N is the total number of subjects who are evaluable for response by RECIST criteria.
Measured: Up to 4 years
Progression free survival (PFS)
The time interval between the date of first dose of IP until disease progression or death, whichever occurs first.
Measured: Up to 4 years
Overall Survival (OS)
OS is defined as the time interval between the date of first dose of IP and the date of death.
Measured: Up to 4 years
Percentage of subjects with symptom improvement
The Pancreatic cancer symptom management using: Functional Assessment Solid Tumors Hepatobiliary Symptom Index-8 (FHSI-8) questionaire will evaluate individual symptom improvement from baseline will be analyzed by different levels of improvement separately, ie, by reduction of score 1, 2, 3, and 4. At any given follow-up time point, the subject is classified having symptom improvement if the subject has reduced symptom severity compared to baseline regardless of subsequent symptom score.
Measured: Up to 4 years
Percentage of subjects with symptom improvement between subjects who experienced at least partial response and those without partial response
The FHSI-8 assessment will measure the correlation of symptom improvement between those who experienced a Partial Response (PR) to those without a PR.
Measured: Up to 4 years
Percentage of subjects who experienced symptom improvement by a score of ≥ 2
The FHSI-8 assessment will measure the correlation of symptom improvement with Eastern Cooperative Oncology Group (ECOG) performance status (PS) over the course of treatment
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2015 (estimated)
- Study start18 Jan 2016
- Primary completion29 Oct 2018
- Study completion29 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Pancreas AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by CelgeneThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chrystal Louis, MD, Study director, Celgene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02620800
- Sponsor's protocol ID
- ABI-007-PANC-009
- Acronym
- FABLOx
- Status last verified
- Oct 2019
- First submitted
- 30 Nov 2015
- Last updated
- 22 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Multicenter, Single Arm, Phase 1/2 Trial of Metronomic 5-fluorouracil in Combination With Nab-paclitaxel, Bevacizumab, Leucovorin, and Oxaliplatin in Patients With Metastatic Pancreatic Adenocarcinoma.
- ClinicalTrials.gov ID
- NCT02620800
- Acronym / sponsor ID
- FABLOx / ABI-007-PANC-009
- Conditions
- Metastatic Pancreas Adenocarcinoma
- Keywords
- Metastatic Pancreatic Cancer, Adenocarcinoma, Open-label, Phase 1/2, Metronomic, Chemotherapy, ABI-007, nab-paclitaxel
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 18 Jan 2016 (actual)
- Primary completion
- 29 Oct 2018 (actual)
- Study completion
- 29 Oct 2018 (actual)
- First posted
- 3 Dec 2015 (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.
The purpose of this study is to learn about the safety and potential benefit of metronomic 5-fluorouracil in combination with nab®1-paclitaxel, bevacizumab, leucovorin, and oxaliplatin in treating patients with metastatic pancreatic adenocarcinoma.
Detailed description
The Phase 1 portion of the study is an open-label study enrolling subjects with metastatic pancreatic adenocarcinoma who have not previously received systemic chemotherapy at any time as treatment for pancreatic cancer (including adjuvant chemotherapy), except low dose chemotherapy administered as a radiosensitizer concomitant with radiotherapy and to determine the recommended Phase 2 dose (RP2D) and dose-limiting toxicities (DLTs) of metronomic 5-FU in combination with nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma.
Subjects will be enrolled in cohorts of 6 subjects. There will be no dose escalation. Dose limiting toxicities will be assessed in cycle 1. If there is an incidence of ≥2 of 6 subjects experiencing a DLT, the dose will be de-escalated to the next lower dose. Based on the totality of the data, the investigators may advise the Sponsor to evaluate additional subjects at any of the dose levels. Upon Sponsor agreement, if additional subjects are enrolled at any dose level, DLT evaluation will occur at that same ratio (if ≥ 4 of 12 subjects, or ≥ 6 of 18 subjects experience a DLT, the dose will be de-escalated). Approximately 12-24 subjects will be enrolled in the Phase 1 portion of the study, dependent on the number of dose levels examined and the number of subjects enrolled at each dose level.
Safety will continuously be evaluated by incidence of Treatment Emergent Adverse Events (TEAEs) by the Medical Dictionary for Drug Regulatory Activities (MedDRA) and severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 (v4.03).
The Phase 2 part of the study is to determine if the combination of metronomic 5-FU, nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin at the RP2D defined in Phase 1 achieves a clinically meaningful improvement in 1 year survival rate over the historical control. Approximately 60 subjects are planned to be enrolled in the Phase 2 portion of the study.
Subjects may remain on treatment until disease progression, unacceptable toxicity, withdrawal of consent, physician decision, or death. The anticipated duration of the study (including Phase 1, Phase 2 and follow-up) is approximately 4 years.
The Phase 1 portion of the study is an open-label study enrolling subjects with metastatic pancreatic adenocarcinoma who have not previously received systemic chemotherapy at any time as treatment for pancreatic cancer (including adjuvant chemotherapy), except low dose chemotherapy administered as a radiosensitizer concomitant with radiotherapy and to determine the recommended Phase 2 dose (RP2D) and dose-limiting toxicities (DLTs) of metronomic 5-FU in combination with nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma.
Subjects will be enrolled in cohorts of 6 subjects. There will be no dose escalation. Dose limiting toxicities will be assessed in cycle 1. If there is an incidence of ≥2 of 6 subjects experiencing a DLT, the dose will be de-escalated to the next lower dose. Based on the totality of the data, the investigators may advise the Sponsor to evaluate additional subjects at any of the dose levels. Upon Sponsor agreement, if additional subjects are enrolled at any dose level, DLT evaluation will occur at that same ratio (if ≥ 4 of 12 subjects, or ≥ 6 of 18 subjects experience a DLT, the dose will be de-escalated). Approximately 12-24 subjects will be enrolled in the Phase 1 portion of the study, dependent on the number of dose levels examined and the number of subjects enrolled at each dose level.
Safety will continuously be evaluated by incidence of Treatment Emergent Adverse Events (TEAEs) by the Medical Dictionary for Drug Regulatory Activities (MedDRA) and severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 (v4.03).
The Phase 2 part of the study is to determine if the combination of metronomic 5-FU, nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin at the RP2D defined in Phase 1 achieves a clinically meaningful improvement in 1 year survival rate over the historical control. Approximately 60 subjects are planned to be enrolled in the Phase 2 portion of the study.
Subjects may remain on treatment until disease progression, unacceptable toxicity, withdrawal of consent, physician decision, or death. The anticipated duration of the study (including Phase 1, Phase 2 and follow-up) is approximately 4 years.
Upon completion of the Phase 1 portion of the study, a decision not to proceed with the Phase 2 portion was taken by the Sponsor. The decision to terminate the study after Phase 1 was not based on any safety concerns that posed an unacceptable risk for this patient population and no safety issues have been identified.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FABLOx | Experimental | Drug: 5FU, Drug: nab-paclitaxel, Drug: bevacizumab, Drug: calcium leucovorin, Drug: oxaliplatin5 fluorouracil (5-FU ) (180 mg/m^2/day for 14 days), by continuous intravenous infusion (CIVI) via ambulatory pump, nab-paclitaxel (75 mg/m^2) as a 30-minute (min) IV infusion on Days 1, 8, and 15, bevacizumab (5 mg/kg) as an IV infusion on Days 1 and 15, calcium leucovorin (20 mg/m^2) IV bolus on Days 1, 8, 15, and oxaliplatin (40 mg/m^2) as a 60-min IV infusion on Days 1, 8, and 15. First bevacizumab infusion is given over 90 minutes. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- A subject will be eligible for inclusion in this study only if all of the following criteria are met:
- Male or female subject is between 18 and 65 years of age at the time of signing the Informed Consent Form (ICF).
- Subject has definitive histologically or cytologically confirmed metastatic pancreatic adenocarcinoma.
- Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
- Subject has one or more tumors measurable by CT scan (or (MRI), if allergic to CT contrast media) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Key exclusion criteria (29 listed)
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- Subject has received previous systemic chemotherapy or investigational therapy (other than that as a radiosensitizer concomitant with radiotherapy) for the treatment of pancreatic adenocarcinoma, including neo-adjuvant or adjuvant therapy.
- Subject has known brain metastases unless previously treated and controlled for a minimum of 2 weeks prior to enrollment. Subject is not receiving corticosteroids with no evidence of cerebral edema.
- Pre-existing peripheral neuropathy > Grade 1
- Subject with unstable stent.
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 |
|---|---|---|
| 5FU5 fluorouracil (5-FU) (180 mg/m^2/day for 14 days) by CIVI via ambulatory pump | Drug | FABLOx |
| nab-paclitaxelAlso: Abraxane, ABI-007nab-paclitaxel (75 mg/m^2) as a 30-minute (min) IV infusion on Days 1, 8, and 15 | Drug | FABLOx |
| bevacizumabAlso: Avastinbevacizumab (5 mg/kg) as an IV infusion on Days 1 and 15 | Drug | FABLOx |
| calcium leucovorinAlso: Citrovorum Factor, Folinic Acidcalcium leucovorin (20 mg/m^2) IV bolus, on Days 1, 8, 15 | Drug | FABLOx |
| oxaliplatinAlso: Elotaxinoxaliplatin (40 mg/m^2) as a 60-min IV infusion on Days 1, 8, and 15 | Drug | FABLOx |
Primary outcome
Dose limiting toxicities (Phase 1)
Time frame: Up to Day 1 of Cycle 2
• Any toxicity starting during the first 28 days of treatment and requiring 14 days or more of treatment interruption • Grade 3 or 4 neutropenia associated with fever > 38.5°C • Grade 3 anemia requiring a transfusion • Any Grade 4 hematological toxicity lasting > 7 days • Grade 4 thrombocytopenia or a Grade 3 or 4 thrombocytopenia associated with clinically significant bleeding • Grade 3 or 4 non-hematological toxicity with the exception of fatigue, due to any of the study drugs and unresponsive to medical treatment within 4 days of onset • Subjects who experience Grade ≥ 3 hyperbilirubinemia as an apparent DLT. If a Phase 1 subject experiences a Grade ≥ 3 hyperbilirubinemia due principally to unconjugated bilirubin, it will not be defined as a DLT. The subject will be removed from the study and the Phase 1 subject will be replaced. • Any non-hematologic toxicity delaying the initiation of cycle 2 by > 21 days • Grade ≥ 2 pneumonitis or interstitial lung disease
1 year survival rate (Phase II portion)
Time frame: Up to 1 year
1 year survival rate is defined as the time interval between the date of first dose of Investigational Product (IP) and the date of death.
Number of subjects experiencing Adverse Events (AEs) by severity and overall tabulations by cohort and overall including treatment emergent and Serious AEs
Time frame: Up to 4 years
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. All AEs will be recorded by the Investigator from the time the subject signs informed consent until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to Investigational Product.
7 secondary outcomes
Summary for the number of subjects experiencing Adverse Events (AEs) by severity and overall in tabulations by cohort and overall including treatment emergent AEs and Serious AEs
Time frame: Up to 4 years
Objective Response Rate using Response Evaluation Criteria In Solid Tumours (Recist) v1.1 presented by frequency and percentages
Time frame: Up to 4 years
Progression free survival (PFS)
Time frame: Up to 4 years
Overall Survival (OS)
Time frame: Up to 4 years
Percentage of subjects with symptom improvement
Time frame: Up to 4 years
Percentage of subjects with symptom improvement between subjects who experienced at least partial response and those without partial response
Time frame: Up to 4 years
Percentage of subjects who experienced symptom improvement by a score of ≥ 2
Time frame: Up to 4 years
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 22 Oct 2019.
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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.
Chrystal Louis, MD study director
Celgene
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 5FU, nab-paclitaxel and bevacizumab in people with Metastatic Pancreas Adenocarcinoma, run by Celgene at 7 sites in United States.
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 23 inclusion and 29 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 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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 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.
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 limiting toxicities (Phase 1) (time frame: Up to Day 1 of Cycle 2). The study lists 3 primary outcomes in all. 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 22 Oct 2019.