Pancreatic CancerPhase 2OVERPASSNCT05861336
GEM+Nab-Paclitaxel Plus Losartan Followed by Stereotactic Radiotherapy for Locally Advanced Pancreatic Cancer
A Phase 2 study testing Losartan, Gemcitabine and Nab paclitaxel in people with Pancreatic Cancer, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 2 sites in Italy.
Trial summary
Single-arm, prospective, phase II study to evaluate safety and activity of an induction therapy with Gemcitabine (GEM) and nab-paclitaxel plus Losartan followed by Stereotactic Radiotherapy (SBRT) in patients affected by Locally Advanced Pancreatic Cancer (LAPC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Losartan, Gemcitabine and Nab paclitaxel
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesItaly
- Study dates
- 14 Jun 2023to 23 Dec 2024
- Phase
- Phase 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
- Patients with histologically or cytologically confirmed pancreatic carcinoma
- Clinical stage I-III, according to tumor, nodes and metastases (TNM) 8th ed.
- Locally advanced disease, as defined per National Comprehensive Cancer Network (NCCN) Guidelines version 1.2022 (Appendix D)
- Baseline systolic blood pressure (SBP) ≥ 100 mmHg (baseline SBP will be documented during the enrolment visit in a resting, seated position at least five minutes apart; SBP will be established as the average of the two readings; if SBP is borderline it may be measured in the other arm);
- Age >18 years and ≤75 years.
- Life expectancy greater than 12 weeks.
Show all 11Show fewer
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Presence of at least one measurable lesion in agreement to RECIST 1.1 criteria
- Patients must have normal organ and marrow function as defined below:
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence, prior to study entry and continuing throughout the study period and for 6 months after final study drug administration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Clinical stage IV, according to TNM 8th ed.
- Patients who have previously received chemotherapy or radiotherapy for pancreatic cancer.
- Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agent used in the study.
- Serious concomitant systemic disorders incompatible with the study (at discretion of the investigator);
- Patient already treated on other Losartan dosages than those prescribed by protocol or treated on other Angiotensin II Receptor Blockers (ARB) therapy for hypertension or renal protection (with diabetes) at the time of enrolment;
- Baseline hypotension, defined as systolic BP lower than 100 mmHg on two readings obtained on two separated days prior to study enrolment.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
U.O. Radioterapia IRCCS IRST
Meldola, Forlì, 47014
UO Oncologia, AUSL della Romagna
Ravenna, 48121
About this study
Official title: Phase II Study of Gemcitabine Plus Nab-Paclitaxel in Combination With Losartan Followed by Stereotactic Radiotherapy for Locally Advanced Pancreatic Cancer: OVERPASS Trial
Single-arm, prospective, phase II study to evaluate safety and activity of an induction therapy with Gemcitabine (GEM) and nab-paclitaxel plus Losartan followed by Stereotactic Radiotherapy (SBRT) in patients affected by Locally Advanced Pancreatic Cancer (LAPC).
Read the detailed description
Pancreatic cancer (PC) is a malignant disease presenting high mortality rates, with a 5-year survival of about 11%, partly because of its known resistance to Chemotherapy (CHT) and Radiotherapy (RT). Radiation therapy in locally advanced and borderline resectable pancreatic cancer improves only local control as demonstrated by 5 studies published from 1980 to 2011 and confirmed by the more recent LAP-07 trial, which investigated conventional RT after induction CHT with the same results.
Losartan was administered because it indirectly affects tumor microenvironment mechanisms of chemo- and radioresistance. PC cells, through transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF) and Angiotensin II activating signaling pathways lead to tumor microenvironment (TME) cells activation, like pancreatic stellate cells, which play a key role in chemoresistance. Angiotensin system and TGF-β increase and maintain the extracellular matrix, which acts as a barrier against drugs. Murphy et al. showed that Losartan administration during chemotherapy resulted in an effective decrease in plasma levels of TGF-β. Their unexpected successful results suggest that targeting not only tumor but also TME might be a novel treatment paradigm.
The purpose of this study is to prospectively evaluate the safety and activity, in terms of resectability rate, of GEM-nab-paclitaxel chemotherapy with concurrent Losartan followed by SBRT in patients with LAPC.
Secondary endpoints are margin-negative resection rate (R0), progression-free survival (PFS), overall survival (OS), blood biomarkers response, safety and quality of life. A Carbohydrate antigen-19.9 (CA19.9) reduction ≥15% from baseline to the end of induction therapy and Carcinoma embryonic antigen (CEA) are tested as a reliable prognostic factor.
- Conditions
- Pancreatic Cancer
- Being tested
- Losartan, Gemcitabine, Nab paclitaxel, Stereotactic Body Radiation Therapy
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Losartan will be administered at the dose of 25 mg PO qd starting on Cycle 1 Day 1. If this dose will be tolerated during week 1, escalation to 50 mg PO qd at Cycle 1 Day 8
GemcitabineDrug
Gemcitabine 1000 mg/m2 on days 1, 8 and 15 every 28 days
Nab paclitaxelDrug
nab-paclitaxel 125 mg/m2 on days 1, 8, and 15
Stereotactic Body Radiation TherapyRadiation
7 consecutive fractions for a total dose of 35-42 Gy
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy+Losartan+Stereotactic Radiation | Experimental | Chemotherapy will be administered for six cycles as per clinical practice (nab-paclitaxel and gemcitabine: nab-paclitaxel 125 mg/m2 on days 1, 8, and 15, Gemcitabine 1000 mg/m2 on days 1, 8 and 15 every 28 days) Losartan will be administered per os every day during induction chemotherapy and maintained until starting SBRT.
SBRT will be administered in 7 consecutive fractions for a total dose of 35-42 Gy if no progression will be observed after induction therapy. Receives: Drug: Losartan; Drug: Gemcitabine; Drug: Nab paclitaxel; Radiation: Stereotactic Body Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants discontinuing study treatment due to treatment related grade≥3 non-hematological adverse event [Toxicity]
Toxicity-related discontinuation is defined as:
for chemotherapy + losartan phase, discontinuation due to a treatment-related ≥grade3 non-hematological adverse event; Toxicity assessments will be done using the NCI Common Terminology Criteria for Adverse Events v 5.0.
Measured: 40 months
Number of participants discontinuing study treatment due to treatment related grade≥3 adverse event [Toxicity]
Toxicity-related discontinuation is defined as:
for SBRT phase, discontinuation due to a ≥grade3 Adverse Events (Enteritis, Gastritis, Malabsorption, Nausea) occurring for three consecutive days.
Toxicity assessments will be done using the NCI Common Terminology Criteria for Adverse Events v 5.0.
Measured: 40 months
Resectability rate
Rate of patients undergoing surgery on total patient population. Resectability will be determined by Multidisciplinary team according
Measured: 40 months
Secondary outcomes (6)
margin-negative resection rate (R0)
Rate of negative margin resection determined by final pathology of the surgical specimen
Measured: 80 months
progression-free survival (PFS)
Progression-free survival will be defined as the time from the start date of protocol therapy to first objective documentation of progressive disease (distant or local) or death due to any cause or last tumor evaluation
Measured: 80 months
overall survival (OS)
Overall survival will be calculated as the time from the start date of protocol therapy to date of death due to any cause or last follow-up
Measured: 80 months
biomarker blood response
A CA19.9 reduction ≥15% from baseline to the end of induction therapy and CEA are tested as a reliable prognostic factor
Measured: 80 months
Incidence of Treatment-Emergent Adverse Events [Toxicity]
All patient will be evaluated for toxicity using the NCI Common Terminology Criteria for Adverse Events (CTCAE v 5.0). All patients will be evaluated for toxicity after each therapy session. Toxicity analyses will be performed on all patients who received at least one dose of study treatment.
Frequency tables will be performed for all categorical variables. Continuous variables will be presented using the median and range.
Measured: 80 months
Quality of life questionnaire (QLQ)
Quality of Life will be measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire that is a patient-reported outcome measure used to assess health-related quality of life in patients undergoing cancer therapy. The scale ranging from 1-4, where 1 is labeled 'Good quality of life,' and 4 is labeled 'Bad quality of life'.
Measured: 80 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2023
- Study start14 Jun 2023
- Primary completion23 Dec 2024
- Study completion23 Dec 2024
Why it stopped: No patients enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antonino Romeo, MD, Principal investigator, IRCCS IRST
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05861336
- Sponsor's protocol ID
- IRST157.04
- Acronym
- OVERPASS
- Status last verified
- Dec 2024
- First submitted
- 21 Mar 2023
- Last updated
- 27 Dec 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Gemcitabine Plus Nab-Paclitaxel in Combination With Losartan Followed by Stereotactic Radiotherapy for Locally Advanced Pancreatic Cancer: OVERPASS Trial
- ClinicalTrials.gov ID
- NCT05861336
- Acronym / sponsor ID
- OVERPASS / IRST157.04
- Conditions
- Pancreatic Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No patients enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSUniversity, hospital or other
- Study start
- 14 Jun 2023 (actual)
- Primary completion
- 23 Dec 2024 (actual)
- Study completion
- 23 Dec 2024 (actual)
- First posted
- 16 May 2023 (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.
Single-arm, prospective, phase II study to evaluate safety and activity of an induction therapy with Gemcitabine (GEM) and nab-paclitaxel plus Losartan followed by Stereotactic Radiotherapy (SBRT) in patients affected by Locally Advanced Pancreatic Cancer (LAPC).
Detailed description
Pancreatic cancer (PC) is a malignant disease presenting high mortality rates, with a 5-year survival of about 11%, partly because of its known resistance to Chemotherapy (CHT) and Radiotherapy (RT). Radiation therapy in locally advanced and borderline resectable pancreatic cancer improves only local control as demonstrated by 5 studies published from 1980 to 2011 and confirmed by the more recent LAP-07 trial, which investigated conventional RT after induction CHT with the same results.
Losartan was administered because it indirectly affects tumor microenvironment mechanisms of chemo- and radioresistance. PC cells, through transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF) and Angiotensin II activating signaling pathways lead to tumor microenvironment (TME) cells activation, like pancreatic stellate cells, which play a key role in chemoresistance. Angiotensin system and TGF-β increase and maintain the extracellular matrix, which acts as a barrier against drugs. Murphy et al. showed that Losartan administration during chemotherapy resulted in an effective decrease in plasma levels of TGF-β. Their unexpected successful results suggest that targeting not only tumor but also TME might be a novel treatment paradigm.
The purpose of this study is to prospectively evaluate the safety and activity, in terms of resectability rate, of GEM-nab-paclitaxel chemotherapy with concurrent Losartan followed by SBRT in patients with LAPC.
Secondary endpoints are margin-negative resection rate (R0), progression-free survival (PFS), overall survival (OS), blood biomarkers response, safety and quality of life. A Carbohydrate antigen-19.9 (CA19.9) reduction ≥15% from baseline to the end of induction therapy and Carcinoma embryonic antigen (CEA) are tested as a reliable prognostic factor.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy+Losartan+Stereotactic Radiation | Experimental | Drug: Losartan, Drug: Gemcitabine, Drug: Nab paclitaxel, Radiation: Stereotactic Body Radiation TherapyChemotherapy will be administered for six cycles as per clinical practice (nab-paclitaxel and gemcitabine: nab-paclitaxel 125 mg/m2 on days 1, 8, and 15, Gemcitabine 1000 mg/m2 on days 1, 8 and 15 every 28 days) Losartan will be administered per os every day during induction chemotherapy and maintained until starting SBRT. SBRT will be administered in 7 consecutive fractions for a total dose of 35-42 Gy if no progression will be observed after induction therapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with histologically or cytologically confirmed pancreatic carcinoma
- Clinical stage I-III, according to tumor, nodes and metastases (TNM) 8th ed.
- Locally advanced disease, as defined per National Comprehensive Cancer Network (NCCN) Guidelines version 1.2022 (Appendix D)
- Baseline systolic blood pressure (SBP) ≥ 100 mmHg (baseline SBP will be documented during the enrolment visit in a resting, seated position at least five minutes apart; SBP will be established as the average of the two readings; if SBP is borderline it may be measured in the other arm);
- Age >18 years and ≤75 years.
Key exclusion criteria (8 listed)
- Clinical stage IV, according to TNM 8th ed.
- Patients who have previously received chemotherapy or radiotherapy for pancreatic cancer.
- Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agent used in the study.
- Serious concomitant systemic disorders incompatible with the study (at discretion of the investigator);
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 |
|---|---|---|
| LosartanLosartan will be administered at the dose of 25 mg PO qd starting on Cycle 1 Day 1. If this dose will be tolerated during week 1, escalation to 50 mg PO qd at Cycle 1 Day 8 | Drug | Chemotherapy+Losartan+Stereotactic Radiation |
| GemcitabineGemcitabine 1000 mg/m2 on days 1, 8 and 15 every 28 days | Drug | Chemotherapy+Losartan+Stereotactic Radiation |
| Nab paclitaxelnab-paclitaxel 125 mg/m2 on days 1, 8, and 15 | Drug | Chemotherapy+Losartan+Stereotactic Radiation |
| Stereotactic Body Radiation Therapy7 consecutive fractions for a total dose of 35-42 Gy | Radiation | Chemotherapy+Losartan+Stereotactic Radiation |
Primary outcome
Number of participants discontinuing study treatment due to treatment related grade≥3 non-hematological adverse event [Toxicity]
Time frame: 40 months
Toxicity-related discontinuation is defined as: for chemotherapy + losartan phase, discontinuation due to a treatment-related ≥grade3 non-hematological adverse event; Toxicity assessments will be done using the NCI Common Terminology Criteria for Adverse Events v 5.0.
Number of participants discontinuing study treatment due to treatment related grade≥3 adverse event [Toxicity]
Time frame: 40 months
Toxicity-related discontinuation is defined as: for SBRT phase, discontinuation due to a ≥grade3 Adverse Events (Enteritis, Gastritis, Malabsorption, Nausea) occurring for three consecutive days. Toxicity assessments will be done using the NCI Common Terminology Criteria for Adverse Events v 5.0.
Resectability rate
Time frame: 40 months
Rate of patients undergoing surgery on total patient population. Resectability will be determined by Multidisciplinary team according
6 secondary outcomes
margin-negative resection rate (R0)
Time frame: 80 months
progression-free survival (PFS)
Time frame: 80 months
overall survival (OS)
Time frame: 80 months
biomarker blood response
Time frame: 80 months
Incidence of Treatment-Emergent Adverse Events [Toxicity]
Time frame: 80 months
Quality of life questionnaire (QLQ)
Time frame: 80 months
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 27 Dec 2024.
- 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.
Antonino Romeo, MD principal investigator
IRCCS IRST
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Losartan, Gemcitabine and Nab paclitaxel in people with Pancreatic Cancer, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 2 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 11 inclusion and 8 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 27 Dec 2024. 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 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 phase mean?
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 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?
Number of participants discontinuing study treatment due to treatment related grade≥3 non-hematological adverse event [Toxicity] (time frame: 40 months). 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 27 Dec 2024.