Cancer of PancreasPhase 1/2NCT02902484
Study of Nintedanib and Chemotherapy for Advanced Pancreatic Cancer
A Phase 1/2 study testing Nintedanib in people with Cancer of Pancreas, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
The study will perform a clinical study evaluating the safety and tolerability of nintedanib when combined with standard chemotherapy (Gemcitabine + nab-Paclitaxel) for metastatic pancreatic cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Pancreas
- What is being tested?
- Nintedanib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Sep 2017to 26 Oct 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated written informed consent prior to admission to the study;
- Histologically or cytologically confirmed metastatic or locally advanced adenocarcinoma of the pancreas;
- At least one measurable disease lesion according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1);
- Age ≥ 18 years;
- No more than one prior line of non-gemcitabine/nab-paclitaxel containing systemic therapy for metastatic/locally advanced pancreatic cancer;
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1;
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- Women of childbearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to registration; (Note: contraception in patients with reproductive capacity will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.)
- Adequate biological parameters at baseline (obtained within 14 days prior to registration).
- If elevated liver function tests develop at the time of initial presentation or develop during workup and are the result of mechanical obstruction of the biliary drainage by tumor compression or invasion, a biliary drain may be placed. If drainage allows the liver function tests to come within inclusion criteria, the patient may be enrolled.
Who cannot join
- More than one systemic therapy regimen of any type for metastatic or locally advanced disease. Adjuvant gemcitabine that ended more than 6 months from diagnosis of recurrent disease is not considered as a regimen;
- Prior treatment with nintedanib or any other VEGFR inhibitor;
- Known hypersensitivity to nintedanib, gemcitabine and nab-Paclitaxal peanut or soya or any other trial drug, their excipients or to contrast media;
- Chemo-, hormon-, radio-(except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug;
- Radiotherapy to the target lesion within the past 3 months prior to baseline imaging
- Persistence of clinically relevant therapy related toxicity from previous chemo and/or radiotherapy;
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- Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomization);
- Leptomeningeal disease;
- Radiographic evidence of cavitary or necrotic tumors;
- Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial;
- Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325mg per day);
- Major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period;
- History of clinically significant hemorrhagic or thromboembolic event in the past 6 months;
- Known inherited predisposition to bleeding or thrombosis;
- Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion);
- Proteinuria CTCAE grade 2 or greater;
- Creatinine > 1.5 x ULN or GFR < 45 mL/min;
- Hepatic function: total bilirubin outside of normal limits; ALT or AST > 1.5 ULN in pts without liver metastasis. For Pts with liver metastasis: total bilirubin outside of normal limits, ALT or AST > 2.5 ULN;
- Coagulation parameters: International Normalized Ratio (INR) > 2, prothrombin time (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN;
- Absolute neutrophil count (ANC) < 1500/mL, platelets < 100,000/mL, Hemoglobin < 9.0 g/dl;
- Any known active cancer other than pancreatic primary;
- Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy;
- Active or chronic hepatitis C and/or B infection;
- Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug;
- Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study;
- Pregnancy or breast feeding female;
- Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule;
- Active alcohol or drug abuse;
- Significant weight loss (> 20% of BW) within past 6 months prior to inclusion into the trial or actual body weight of less than 50 kg;
- Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectable, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner for participating females, condoms for participating males) during the trial and for at least three months after end of active therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75063
About this study
Official title: A Phase 1b and Pharmacodynamic Study of Nintedanib Monotherapy for Advanced Pancreatic Cancer
The study will perform a clinical study evaluating the safety and tolerability of nintedanib when combined with standard chemotherapy (Gemcitabine + nab-Paclitaxel) for metastatic pancreatic cancer. It will utilize advanced imaging correlates including dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) which correlates with tumor grade and microvessel density.
Read the detailed description
Preclinical data suggest nintedanib inhibits primary tumor growth in in vivo xenograft models of pancreatic cancer, as well as inhibiting metastasis in pancreatic cancer models. This effect appears primarily due to nintedanib anti-angiogenic properties. The study will perform a clinical study evaluating the safety and tolerability of nintedanib when combined with standard chemotherapy (Gemcitabine + nab-Paclitaxel) for metastatic pancreatic cancer. It will utilize advanced imaging correlates including dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) which correlates with tumor grade and microvessel density.
For each patient, treatment will have two phases: nintedanib monotherapy for a two week period (Days 1-14) followed by combination phase of nintedanib plus chemotherapy (Cycle 2+).
- Conditions
- Cancer of Pancreas
- Being tested
- Nintedanib
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NintedanibDrug
Also called Ofev, Vargatef
Nintedanib Monotherapy Followed by Combination Therapy of Nintedanib and Gemcitabine Plus nab-Paclitaxel
| Study group | Role | What they receive |
|---|---|---|
| Nintedanib Monotherapy | Experimental | One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first.
1. Nintedanib dose escalation: 150, 200 mg PO BID
2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days
3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days Receives: Drug: Nintedanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
A standard 3+3 phase 1 trial design will be used for Nintedanib monotherapy for a two week period (Days 1-14) followed by combination therapy of nintedanib plus chemotherapy. Two dose levels of nintedanib will be explored 150 mg BID and 200 mg BID. The combination phase will include gemcitabine + nab-paclitaxel, and nintedanib. Treatment will be administered intravenously on days 1, 8, 15 every 28 days.
One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first.
- Nintedanib dose escalation: 150 mg PO BID and 200mg PO BID
- Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days
- Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days
MTD assessed after combination therapy.
Measured: Each 28 day cycle for up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2016 (estimated)
- Study start7 Sep 2017
- Primary completion26 Oct 2021
- Study completion26 Oct 2021
Why it stopped: The study was terminated due to futility and lack of future funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cancer of PancreasStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim, The University of Texas Health Science Center at San Antonio, South Plains Oncology Consortium
- Responsible party
- Principal investigator, Salwan Al Mutar MD MS, University of Texas Southwestern Medical Center
- Investigators
- Salwan Al Mutar, MD, Principal investigator, UT Southwestern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02902484
- Sponsor's protocol ID
- STU 022016-083
- Status last verified
- May 2024
- First submitted
- 2 Sep 2016
- Last updated
- 3 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b and Pharmacodynamic Study of Nintedanib Monotherapy for Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT02902484
- Acronym / sponsor ID
- STU 022016-083
- Conditions
- Cancer of Pancreas
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to futility and lack of future funding
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim, The University of Texas Health Science Center at San Antonio, South Plains Oncology Consortium
- Study start
- 7 Sep 2017 (actual)
- Primary completion
- 26 Oct 2021 (actual)
- Study completion
- 26 Oct 2021 (actual)
- First posted
- 15 Sep 2016 (estimated)
- Results
- Posted 3 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will perform a clinical study evaluating the safety and tolerability of nintedanib when combined with standard chemotherapy (Gemcitabine + nab-Paclitaxel) for metastatic pancreatic cancer. It will utilize advanced imaging correlates including dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) which correlates with tumor grade and microvessel density.
Detailed description
Preclinical data suggest nintedanib inhibits primary tumor growth in in vivo xenograft models of pancreatic cancer, as well as inhibiting metastasis in pancreatic cancer models. This effect appears primarily due to nintedanib anti-angiogenic properties. The study will perform a clinical study evaluating the safety and tolerability of nintedanib when combined with standard chemotherapy (Gemcitabine + nab-Paclitaxel) for metastatic pancreatic cancer. It will utilize advanced imaging correlates including dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) which correlates with tumor grade and microvessel density.
For each patient, treatment will have two phases: nintedanib monotherapy for a two week period (Days 1-14) followed by combination phase of nintedanib plus chemotherapy (Cycle 2+).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nintedanib Monotherapy | Experimental | Drug: NintedanibOne cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 150, 200 mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed and dated written informed consent prior to admission to the study;
- Histologically or cytologically confirmed metastatic or locally advanced adenocarcinoma of the pancreas;
- At least one measurable disease lesion according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1);
- Age ≥ 18 years;
- No more than one prior line of non-gemcitabine/nab-paclitaxel containing systemic therapy for metastatic/locally advanced pancreatic cancer;
Key exclusion criteria (30 listed)
- More than one systemic therapy regimen of any type for metastatic or locally advanced disease. Adjuvant gemcitabine that ended more than 6 months from diagnosis of recurrent disease is not considered as a regimen;
- Prior treatment with nintedanib or any other VEGFR inhibitor;
- Known hypersensitivity to nintedanib, gemcitabine and nab-Paclitaxal peanut or soya or any other trial drug, their excipients or to contrast media;
- Chemo-, hormon-, radio-(except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug;
- Radiotherapy to the target lesion within the past 3 months prior to baseline imaging
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 |
|---|---|---|
| NintedanibAlso: Ofev, VargatefNintedanib Monotherapy Followed by Combination Therapy of Nintedanib and Gemcitabine Plus nab-Paclitaxel | Drug | Nintedanib Monotherapy |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Each 28 day cycle for up to 2 years
A standard 3+3 phase 1 trial design will be used for Nintedanib monotherapy for a two week period (Days 1-14) followed by combination therapy of nintedanib plus chemotherapy. Two dose levels of nintedanib will be explored 150 mg BID and 200 mg BID. The combination phase will include gemcitabine + nab-paclitaxel, and nintedanib. Treatment will be administered intravenously on days 1, 8, 15 every 28 days. One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 150 mg PO BID and 200mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days MTD assessed after combination therapy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Salwan Al Mutar, MD principal investigator
UT Southwestern
1 site 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 Nintedanib in people with Cancer of Pancreas, run by University of Texas Southwestern Medical Center at 1 site 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 9 inclusion and 30 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: stopped early, as of the sponsor's last update on 3 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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?
Yes. Results are posted in the registry (first posted 3 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) (time frame: Each 28 day cycle for up to 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 3 Jun 2024.