Metastatic Urothelial CarcinomaPhase 2NCT03464734
Pembrolizumab and Nab Paclitaxel in Patients With Metastatic Urothelial Carcinoma
A Phase 2 study testing Pembrolizumab and Nanoparticle Albumin-bound Paclitaxel in people with Metastatic Urothelial Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 2 sites in Italy.
Trial summary
This phase II, single-center study will assess the efficacy of pembrolizumab + nab-paclitaxel in patients who have metastatic urothelial tumor and do not respond to chemotherapy. The time between drug administration and progression of the disease will be assessed to determine if the drug will work. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Urothelial Carcinoma
- What is being tested?
- Pembrolizumab and Nanoparticle Albumin-bound Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 2 sitesItaly
- Study dates
- 16 Jan 2019to 21 Jan 2020
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent/assent for the trial, and be willing and able to follow trial procedures.
- Be 18 years-old on day of signing informed consent.
- Have an histologically-confirmed diagnosis of UC of the bladder or the urothelium, originating from either the bladder or the urinary tract (including upper tract), with predominant (>50%) UC component if other divergent histologies (e.g. squamous cell carcinoma, adenocarcinoma, small cell carcinoma) are found.
- Have a life expectancy of at least 12 weeks.
- Have experienced failure of 1 or 2 platinum-based conventional chemotherapy regimens for metastatic disease (2nd-to-3rd line only); a relapse should be occurred within 6 months from the last cycle of chemotherapy.
- Have measurable disease based on RECIST 1.1.
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- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may provide an archived specimen.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- Demonstrate adequate organ function.
- (Female subject of childbearing potential) Have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- (Female subjects of childbearing potential ) Be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
- (Male subjects of childbearing potential) Agree to use an adequate method of contraception, starting from the first dose of study therapy through 120 days after the last dose of study therapy.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has a known history of active Bacillus Tuberculosis
- Had prior administration of taxane-based chemotherapy
- Is taking regular oral steroids, above the allowed limit of 10mg/day methylprednisolone or analogues, for any reason. Patients must not have had steroids for 28 days prior to study entry
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., Grade ≤1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
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- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent
- Note: Subjects with Grade ≤2 neuropathy are an exception to this criterion and may qualify for the study
- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- Has known active Hepatitis B or Hepatitis C
- Has received a live vaccine within 30 days of planned start of study therapy
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Clinical Trial Center, Istituto Nazionale dei Tumori di Milano
Milan, 20133
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
About this study
Official title: An Open Label, Single-arm, Phase 2 Study of Pembrolizumab and Nanoparticle Albumin-bound Paclitaxel in Patients With Metastatic Urothelial Carcinoma After Chemotherapy Failure; the PEANUT Study
This phase II, single-center study will assess the efficacy of pembrolizumab + nab-paclitaxel in patients who have metastatic urothelial tumor and do not respond to chemotherapy. The time between drug administration and progression of the disease will be assessed to determine if the drug will work.
Read the detailed description
In an open-label, single-arm, single-center, phase 2 trial, patients will receive pembrolizumab 200 mg intravenously (IV) on D1 and nab paclitaxel at the dose of 125 mg/m2 IV on D1 and D8. Cycles are repeated every 3 weeks until PD or onset of unacceptable toxicity. Key inclusion criteria are: predominant UC, failure of maximum 2 platinum-based CT regimens for metastatic disease (2nd-to-3rd line only). Neoadjuvant/adjuvant CT is counted if relapse occurred 6 months of the last CT cycle. Response is evaluated by RECIST criteria v.1.1 every 2 cycles. PD-L1 expression will be prospectively assessed on both immune cells (IC) and tumor cells at a centralized laboratory (National Cancer Institute Milano). Combined positivity score (CPS) for PD-L1 assessment will be used, as previously reported, and the 10% cutoff will be adopted for the analyses. The primary endpoint of the study is the progression-free survival (PFS). The target is to detect an improvement in the median PFS from 3.0 months (H0) to 5.0 months (H1). To achieve 90% power with a one-sided non-parametric test at the 10% significance level, we estimated that 64 patients must be accrued over 18 months, with follow-up duration of 12 months. PFS will be also analyzed according to the PD-L1 expression. Should the above investigation suggest that the treatment benefit is stronger in patients with CPS 10%, there is the option to expand this cohort up to a maximum of 50 patients. As such, we estimate 85% power to detect the target improvement in PFS. The decision of cohort expansion will rely on predictive power (PP) calculation: a PP 30% will be regarded as promising. Translational analyses will include multiparametric flow cytometry of blood samples, gene expression (RNA-seq, Illumina HiSeq) and mutation profiling of tumor samples (Ion Torrent Personal Genome Machine). These profiles will be matched with response to treatment and PFS/overall survival.
- Conditions
- Metastatic Urothelial Carcinoma
- Being tested
- Pembrolizumab and Nanoparticle Albumin-bound Paclitaxel
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab and Nanoparticle Albumin-bound PaclitaxelDrug
At study entry, patients will receive 2 cycles of pembrolizumab at the dose of 200 mg, intravenously in 30 min, on day 1 and nab-paclitaxel 125 mg/m2 intravenously in 30-40 min, on day 1 and 8.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + nab-paclitaxel | Experimental | pembrolizumab 200 mg + nab-paclitaxel 125 mg/m2, intravenously Receives: Drug: Pembrolizumab and Nanoparticle Albumin-bound Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free-survival
Increment of median PFS from 3 months to 5 months, with 10% of statistical significance
Measured: Through study completion, average 4 months
Secondary outcomes (3)
Incidence of all-grade and grade 3-4 side effects
number of patients with adverse events, frequency and type of adverse events
Measured: 9 weeks
Objective response-rate (ORR) to RECIST v1.1 criteria
Rate of complete response + partial response
Measured: 9 weeks
Overall survival
overall survival
Measured: Through study completion, average 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start16 Jan 2019
- Primary completion21 Jan 2020
- Study completion21 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03464734
- Sponsor's protocol ID
- PEANUT
- Status last verified
- Nov 2022
- First submitted
- 19 Feb 2018
- Last updated
- 30 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Giannatempo P, Raggi D, Marandino L, Bandini M, Fare E, Calareso G, Colecchia M, Gallina A, Ross JS, Alessi A, Briganti A, Montorsi F, Madison R, Necchi A. Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma: interim results of the open-label, single-arm, phase II PEANUT study. Ann Oncol. 2020 Dec;31(12):1764-1772. doi: 10.1016/j.annonc.2020.09.012. Epub 2020 Sep 23.
PubMed 32979512
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Single-arm, Phase 2 Study of Pembrolizumab and Nanoparticle Albumin-bound Paclitaxel in Patients With Metastatic Urothelial Carcinoma After Chemotherapy Failure; the PEANUT Study
- ClinicalTrials.gov ID
- NCT03464734
- Acronym / sponsor ID
- PEANUT
- Conditions
- Metastatic Urothelial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- 16 Jan 2019 (actual)
- Primary completion
- 21 Jan 2020 (actual)
- Study completion
- 21 Jan 2020 (actual)
- First posted
- 14 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II, single-center study will assess the efficacy of pembrolizumab + nab-paclitaxel in patients who have metastatic urothelial tumor and do not respond to chemotherapy. The time between drug administration and progression of the disease will be assessed to determine if the drug will work.
Detailed description
In an open-label, single-arm, single-center, phase 2 trial, patients will receive pembrolizumab 200 mg intravenously (IV) on D1 and nab paclitaxel at the dose of 125 mg/m2 IV on D1 and D8. Cycles are repeated every 3 weeks until PD or onset of unacceptable toxicity. Key inclusion criteria are: predominant UC, failure of maximum 2 platinum-based CT regimens for metastatic disease (2nd-to-3rd line only). Neoadjuvant/adjuvant CT is counted if relapse occurred 6 months of the last CT cycle. Response is evaluated by RECIST criteria v.1.1 every 2 cycles. PD-L1 expression will be prospectively assessed on both immune cells (IC) and tumor cells at a centralized laboratory (National Cancer Institute Milano). Combined positivity score (CPS) for PD-L1 assessment will be used, as previously reported, and the 10% cutoff will be adopted for the analyses. The primary endpoint of the study is the progression-free survival (PFS). The target is to detect an improvement in the median PFS from 3.0 months (H0) to 5.0 months (H1). To achieve 90% power with a one-sided non-parametric test at the 10% significance level, we estimated that 64 patients must be accrued over 18 months, with follow-up duration of 12 months. PFS will be also analyzed according to the PD-L1 expression. Should the above investigation suggest that the treatment benefit is stronger in patients with CPS 10%, there is the option to expand this cohort up to a maximum of 50 patients. As such, we estimate 85% power to detect the target improvement in PFS. The decision of cohort expansion will rely on predictive power (PP) calculation: a PP 30% will be regarded as promising. Translational analyses will include multiparametric flow cytometry of blood samples, gene expression (RNA-seq, Illumina HiSeq) and mutation profiling of tumor samples (Ion Torrent Personal Genome Machine). These profiles will be matched with response to treatment and PFS/overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + nab-paclitaxel | Experimental | Drug: Pembrolizumab and Nanoparticle Albumin-bound Paclitaxelpembrolizumab 200 mg + nab-paclitaxel 125 mg/m2, intravenously |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Be willing and able to provide written informed consent/assent for the trial, and be willing and able to follow trial procedures.
- Be 18 years-old on day of signing informed consent.
- Have an histologically-confirmed diagnosis of UC of the bladder or the urothelium, originating from either the bladder or the urinary tract (including upper tract), with predominant (>50%) UC component if other divergent histologies (e.g. squamous cell carcinoma, adenocarcinoma, small cell carcinoma) are found.
- Have a life expectancy of at least 12 weeks.
- Have experienced failure of 1 or 2 platinum-based conventional chemotherapy regimens for metastatic disease (2nd-to-3rd line only); a relapse should be occurred within 6 months from the last cycle of chemotherapy.
Key exclusion criteria (21 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has a known history of active Bacillus Tuberculosis
- Had prior administration of taxane-based chemotherapy
- Is taking regular oral steroids, above the allowed limit of 10mg/day methylprednisolone or analogues, for any reason. Patients must not have had steroids for 28 days prior to study entry
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 |
|---|---|---|
| Pembrolizumab and Nanoparticle Albumin-bound PaclitaxelAt study entry, patients will receive 2 cycles of pembrolizumab at the dose of 200 mg, intravenously in 30 min, on day 1 and nab-paclitaxel 125 mg/m2 intravenously in 30-40 min, on day 1 and 8. | Drug | Pembrolizumab + nab-paclitaxel |
Primary outcome
Progression-free-survival
Time frame: Through study completion, average 4 months
Increment of median PFS from 3 months to 5 months, with 10% of statistical significance
3 secondary outcomes
Incidence of all-grade and grade 3-4 side effects
Time frame: 9 weeks
Objective response-rate (ORR) to RECIST v1.1 criteria
Time frame: 9 weeks
Overall survival
Time frame: Through study completion, average 6 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 30 Nov 2022.
- Derived from this study: PubMed 32979512Giannatempo P, Raggi D, Marandino L, Bandini M, Fare E, Calareso G, Colecchia M, Gallina A, Ross JS, Alessi A, Briganti A, Montorsi F, Madison R, Necchi A. Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma: interim results of the open-label, single-arm, phase II PEANUT study. Ann Oncol. 2020 Dec;31(12):1764-1772. doi: 10.1016/j.annonc.2020.09.012. Epub 2020 Sep 23.
- Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma: interim results of the open-label, single-arm, phase II PEANUT studyLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Pembrolizumab and Nanoparticle Albumin-bound Paclitaxel in people with Metastatic Urothelial Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano 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 12 inclusion and 21 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 30 Nov 2022. 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 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?
Progression-free-survival (time frame: Through study completion, average 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03464734, which also lists 1 linked publication.
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 30 Nov 2022.