Metastatic CancerPhase 2NCT05574504
Phase II Trial of Lurbinectedin Combined With Avelumab as Switch Maintenance Firstline Therapy
A Phase 2 study testing avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin in people with Metastatic Cancer and Urothelial Carcinoma, run by AdventHealth at 1 site in United States.
Trial summary
A nonrandomized phase II trial is proposed combining avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin as switch maintenance therapy for mUC following stable or responding disease on 4-6 cycles of first line platinum-based chemotherapy Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Cancer, Urothelial Carcinoma
- What is being tested?
- avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2023to Nov 2028
- 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
- Patient eligibility should be reviewed and documented by an appropriate member of the investigator's study team before patients are included in the study. Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- Diagnosis:
- Histologically confirmed, unresectable locally advanced or metastatic predominant transitional cell carcinoma of the urothelium.
- Documented Stage IV disease (T4b, N0, M0; any T, N1-N3, M0; any T, any N, M1) at the start of first-line chemotherapy.
- Measurable disease prior to the start of first-line chemotherapy by RECIST v1.1.
- Prior first-line chemotherapy must have completed 4-10 weeks before registration and consisted of at least 4 cycles and no more than 6 cycles of platinum-based chemotherapy. No other chemotherapy regimens are allowed in this study 3. Patients without progressive disease as per RECIST v1.1 guidelines (ie, with an ongoing CR, PR, or SD) following completion of 4 to 6 cycles of first-line chemotherapy.
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- Eligibility based on this criterion will be determined by investigator review of pre-chemotherapy and post-chemotherapy radiological assessments (CT/MRI scans)
- 4. Tumor samples: Provision of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or slides from the most recent primary or metastatic tumor biopsy or resection obtained prior to treatment with first line chemotherapy is desirable (but not mandatory). If an FFPE tissue block cannot be provided, 15 unstained slides of 5 µM sections (10 minimum) will be acceptable.
- 5. Evidence of a signed and dated informed consent document indicating that the patient (or a legally acceptable representative, as allowed by local guideline/practice) has been informed of all pertinent aspects of the study. 6. Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
- 7. Age >18 years. 8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. 9. Adequate bone marrow function, including:
- Absolute neutrophil count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L;
- Platelets ≥100,000/mm3 or ≥100 x 109/L;
- Hemoglobin ≥8 g/dL (may have been transfused). 10. Adequate renal function, defined as estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation.
- 11. Adequate liver function, including: a. Total serum bilirubin ≥1.5 x upper limit of normal (ULN); b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥2.5 x ULN.
- 12. Serum pregnancy test (for females of childbearing potential) negative at screening.
- 13. Male patients able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use 2 highly effective methods of contraception throughout the study and for at least 60 days after the last dose of assigned treatment
Who cannot join
- Patients with any of the following characteristics/conditions will not be included in the study:
- Patients whose disease progressed by RECIST v1.1 on or after first-line chemotherapy for urothelial cancer.
- Prior adjuvant or neoadjuvant therapy within 12 months of registration
- Prior immunotherapy with IL-2, PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
- Major surgery <4 weeks or major radiation therapy <2 weeks prior to randomization. Prior palliative radiotherapy (10 fractions) to metastatic lesion(s) is permitted, provided it has been completed at least 48 hours prior to patient randomization.
- Patients with known symptomatic central nervous system (CNS) metastases requiring steroids. Patients with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable.
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- Persisting toxicity related to prior therapy NCI CTCAE v5.0 Grade >1; however, sensory neuropathy Grade ≤2 is acceptable.
- Diagnosis of any other malignancy within 2 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention (eg, surgery, radiation, or castration), or any other cancer that is felt by the PI to be clinically insignificant not requiring systemic therapy in future.
- Participation in other studies involving investigational drug(s) within 4 weeks prior to randomization. Observational studies are permitted.
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
- Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or symptomatic pulmonary embolism.
- Active infection requiring systemic therapy.
- Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of asthma symptom control per the Global Initiative for Asthma 2015).
- Known prior or suspected hypersensitivity to study drugs or any component in their formulations.
- Current or prior use of immunosuppressive medication within 7 days prior to registration, EXCEPT the following:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection);
- Systemic corticosteroids at physiologic doses equivalent;
- Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
- Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy, or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
- Any test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection.
- Vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivate vaccines (for example, inactivated influenza vaccines).
- Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Jazz Pharma employees directly involved in the conduct of the study.
- Pregnant female patients; breastfeeding female patients; male patients able to father children, and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 60 days after the last dose of investigational product.
- Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, and pneumonitis; psychiatric condition including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
AdventHealth Cancer Institute
Orlando, Florida, 32804
About this study
Official title: Phase II Trial of Lurbinectedin Combined With Avelumab as Switch Maintenance Firstline Therapy for Metastatic Urothelial Carcinoma With Stable or Responding Disease Following Platinum-based Chemotherapy
A nonrandomized phase II trial is proposed combining avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin as switch maintenance therapy for mUC following stable or responding disease on 4-6 cycles of first line platinum-based chemotherapy
Read the detailed description
The purpose of this research is to study benefit of the combination of lurbinectedin chemotherapy with maintenance avelumab immunotherapy in patients with advanced cancer of the urinary tract who have completed platinum-based chemotherapy. Avelumab alone is the usual approach and is already approved by the US FDA for the treatments of patients with this type of cancer. Lurbinectedin is approved for a type of lung cancer, but is not approved for urinary tract cancer.
- Conditions
- Metastatic Cancer, Urothelial Carcinoma
- Being tested
- avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin
- Medical subject headings
- Neoplasm Metastasis, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedinDrug
Avelumab 800 mg IV q 2 weeks (days 1,15, and 29 every 6 week cycle ) (premedication includes a H1 blocker, H2 blocker and Tylenol) Lurbinectedin 3.2 mg/m2 administered as a 1-h intravenous infusion once every 3 weeks (day 1 and 22 every 6 week cycle )
1 cycle= 6 weeks
Premedication for lurbinectedin:
- Corticosteroids (dexamethasone 8 mg intravenously or equivalent)
- Serotonin antagonists (ondansetron 8 mg intravenously or equivalent) Granulocyte-colony stimulating factor (G-CSF) or equivalent per ASCO guidelines per investigator discretion
| Study group | Role | What they receive |
|---|---|---|
| avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin | Experimental | Phase II trial is designed to evaluate the combination of avelumab (800 mg IV every 2 weeks-(days 1,15, and 29 every 6 week cycle ) and lurbinectedin (3·2 mg/m2 lurbinectedin administered as a 1-h intravenous infusion once every 3 weeks-day 1 and 22 every 6 week cycle ) for those with stable or responding disease following 4-6 cycles of platinum-based firstline chemotherapy for mUC with stable or responding disease following 4-6 cycles of platinum-based firstline chemotherapy for mUC. Receives: Drug: avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The combination of lurbinectedin chemotherapy with maintenance avelumab immunotherapy in patients with advanced cancer of the urinary tract
The primary objective of this study is to evaluate the progression-free survival (PFS) with switch maintenance combination of avelumab and lurbinectedin in patients with metastatic urothelial carcinoma with stable or responding disease with 4-6 cycles of platinum-based chemotherapy.
Measured: 32 months
Secondary outcomes (3)
The secondary objectives of this study are to assess:
- Objective response rate (ORR) for those with measurable disease. B. Duration of response (DOR)
Response will be measured using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
Duration of Response is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented, or death due to any cause
Measured: 32 months
Overall Survival (OS)
Overall Survival (OS) is defined as the time from treatment initiation to death due to any cause or censored at date last known alive.
Measured: 32 months
Toxicities, associated with the combination treatment
For safety and tolerability, all adverse events will be graded and analyzed using CTCAE version 5.0. The worst grade will be used if any toxicity event is reported multiple times on the same participant. Any adverse events resulting in discontinuation, dose modification, and/or dosing interruption, and/or treatment delay of drug will also be summarized.
Measured: 32 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2022
- Study start8 May 2023
- Primary completionNov 2026 (estimated)
- Study completionNov 2028 (estimated)
Why it stopped: PI Decision based on no enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic 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
- AdventHealth
- Sponsor type
- University, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Responsible party
- Principal investigator, Guru Sonpavde, AdventHealth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05574504
- Sponsor's protocol ID
- VT# IST-21-11721
- Status last verified
- Jul 2024
- First submitted
- 19 Sep 2022
- Last updated
- 1 Aug 2024
- Results posted
- No
- 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 1 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Lurbinectedin Combined With Avelumab as Switch Maintenance Firstline Therapy for Metastatic Urothelial Carcinoma With Stable or Responding Disease Following Platinum-based Chemotherapy
- ClinicalTrials.gov ID
- NCT05574504
- Acronym / sponsor ID
- VT# IST-21-11721
- Conditions
- Metastatic Cancer, Urothelial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI Decision based on no enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- AdventHealthUniversity, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Study start
- 8 May 2023 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 10 Oct 2022 (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.
A nonrandomized phase II trial is proposed combining avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin as switch maintenance therapy for mUC following stable or responding disease on 4-6 cycles of first line platinum-based chemotherapy
Detailed description
The purpose of this research is to study benefit of the combination of lurbinectedin chemotherapy with maintenance avelumab immunotherapy in patients with advanced cancer of the urinary tract who have completed platinum-based chemotherapy. Avelumab alone is the usual approach and is already approved by the US FDA for the treatments of patients with this type of cancer. Lurbinectedin is approved for a type of lung cancer, but is not approved for urinary tract cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin | Experimental | Drug: avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedinPhase II trial is designed to evaluate the combination of avelumab (800 mg IV every 2 weeks-(days 1,15, and 29 every 6 week cycle ) and lurbinectedin (3·2 mg/m2 lurbinectedin administered as a 1-h intravenous infusion once every 3 weeks-day 1 and 22 every 6 week cycle ) for those with stable or responding disease following 4-6 cycles of platinum-based firstline chemotherapy for mUC with stable or responding disease following 4-6 cycles of platinum-based firstline chemotherapy for mUC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patient eligibility should be reviewed and documented by an appropriate member of the investigator's study team before patients are included in the study. Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- 4. Tumor samples: Provision of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or slides from the most recent primary or metastatic tumor biopsy or resection obtained prior to treatment with first line chemotherapy is desirable (but not mandatory). If an FFPE tissue block cannot be provided, 15 unstained slides of 5 µM sections (10 minimum) will be acceptable.
- 5. Evidence of a signed and dated informed consent document indicating that the patient (or a legally acceptable representative, as allowed by local guideline/practice) has been informed of all pertinent aspects of the study. 6. Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
- 7. Age >18 years. 8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. 9. Adequate bone marrow function, including:
- 11. Adequate liver function, including: a. Total serum bilirubin ≥1.5 x upper limit of normal (ULN); b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥2.5 x ULN.
Key exclusion criteria (24 listed)
- Patients with any of the following characteristics/conditions will not be included in the study:
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 |
|---|---|---|
| avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedinAvelumab 800 mg IV q 2 weeks (days 1,15, and 29 every 6 week cycle ) (premedication includes a H1 blocker, H2 blocker and Tylenol) Lurbinectedin 3.2 mg/m2 administered as a 1-h intravenous infusion once every 3 weeks (day 1 and 22 every 6 week cycle ) 1 cycle= 6 weeks Premedication for lurbinectedin: * Corticosteroids (dexamethasone 8 mg intravenously or equivalent) * Serotonin antagonists (ondansetron 8 mg intravenously or equivalent) Granulocyte-colony stimulating factor (G-CSF) or equivalent per ASCO guidelines per investigator discretion | Drug | avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin |
Primary outcome
The combination of lurbinectedin chemotherapy with maintenance avelumab immunotherapy in patients with advanced cancer of the urinary tract
Time frame: 32 months
The primary objective of this study is to evaluate the progression-free survival (PFS) with switch maintenance combination of avelumab and lurbinectedin in patients with metastatic urothelial carcinoma with stable or responding disease with 4-6 cycles of platinum-based chemotherapy.
3 secondary outcomes
The secondary objectives of this study are to assess:
Time frame: 32 months
Overall Survival (OS)
Time frame: 32 months
Toxicities, associated with the combination treatment
Time frame: 32 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 1 Aug 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin in people with Metastatic Cancer and Urothelial Carcinoma, run by AdventHealth 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 16 inclusion and 24 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 1 Aug 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 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?
The combination of lurbinectedin chemotherapy with maintenance avelumab immunotherapy in patients with advanced cancer of the urinary tract (time frame: 32 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2024.