Phase II Trial of Lurbinectedin Combined With Avelumab as Switch Maintenance Firstline Therapy

NCT05574504 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: VT# IST-21-11721
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Metastatic Cancer; Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  32 months

Secondary Outcomes (3)

• The secondary objectives of this study are to assess:

  32 months

• Overall Survival (OS)

  32 months

• Toxicities, associated with the combination treatment

  32 months

Study Arms (1)

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.

Drug: avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin

Interventions

avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin DRUG

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

avelumab (PD-L1 inhibitor immunotherapy) + lurbinectedin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eligibility based on this criterion will be determined by investigator review of pre-chemotherapy and post-chemotherapy radiological assessments (CT/MRI scans)
• \. 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.
• \. 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.
• \. 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.
• \. 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.
• \. Serum pregnancy test (for females of childbearing potential) negative at screening.
• \. 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

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• AdventHealth: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

AdventHealth Cancer Institute

Orlando, Florida, 32804, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Transitional Cell

Interventions

avelumab; PM 01183

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: October 10, 2022
• Study Start: May 8, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2028
• Last Updated: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)