A Combination of Avelumab and Taxane (AVETAX) for Urothelial Cancer

NCT03575013 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201804833
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the safety and efficacy of the combination of Avelumab, (a fully human anti-programmed death ligand 1 (PD-L1) IgG1 antibody) in combination with a taxane chemotherapy (docetaxel) in patients with metastatic urothelial cancer who are either ineligible to receive cisplatin based chemotherapy, refractory to cisplatin in first line setting or have disease relapse after receiving cisplatin based chemotherapy within a year in the neoadjuvant or adjuvant setting.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

• Dose De-Escalation Phase: To assess dose limiting toxicities (DLTs) using CTCAE v4.03.

  All adverse events (AEs )will be considered in DLT assessment unless an event is clearly unrelated to trial treatment. DLTs for phase 1b only include AEs that are considered possibly, probably, or definitely related to the Docetaxel plus Avelumab regimen which occur during the first 21 days of therapy. All AEs, including DLTs, are to be reported according to instructions in the Study Reference Manual and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

  From the start of treatment up to 5 years

• Dose Expansion Phase: To determine overall response rate (ORR) (complete response [CR] + partial response [PR]) per RECIST v1.1

  Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 will be used to determine ORR.

  From the start of treatment up to 5 years

Secondary Outcomes (2)

• Dose Expansion: To determine radiologic progression-free survival (PFS) per RECIST v1.1 and immune RECIST criteria

  From the start of treatment up to 5 years

• Dose Expansion: To determine ORR per RECIST v1.1

  From the start of treatment up to 5 years

Study Arms (1)

Avelumab and Docetaxel

EXPERIMENTAL

Induction phase: Avelumab (10 mg/kg) + Docetaxel (75 mg/m2) every 3 weeks for 6 cycles Maintenance phase: Avelumab (10 mg/kg) every 2 weeks until disease progression or toxicity

Drug: Avelumab; Drug: Docetaxel

Interventions

Avelumab DRUG

Avelumab is a fully human anti-programmed death ligand 1 (PD-L1) IgG1 antibody

Also known as: MSB0010718C

Avelumab and Docetaxel

Docetaxel DRUG

Docetaxel is a antineoplastic agent belonging to the taxoid family

Also known as: Taxotere

Avelumab and Docetaxel

Eligibility Criteria

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

You may qualify if:

• Age \>/=18 years to 85 years
• Histologically or cytologically confirmed locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra). Additional mixed histologies such as squamous, plasmacytoid, adenocarcinoma, sarcomatoid, papillary, micropapillary are permitted provided the urothelial cancer is the predominant histological component.
• Eligible patients must have had either:
• Progressed after treatment with at least 1 platinum-containing regimen, (e.g., ciplatin or carboplatin plus another agent such as gemcitabine, methotrexate, vinblastine, doxorubicin, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence, or
• Were ineligible for cisplatin-based chemotherapy, with ineligibility to cisplatin defined by impaired renal function (creatinine clearance \< 60 ml/min), a hearing loss of 25 decibels at 2 contiguous frequencies, or grade ≥ 2 peripheral neuropathy or
• Locally advanced or metastatic bladder cancer whose disease has progressed within 12 months of neoadjuvant or adjuvant chemotherapy.
• Biopsy material is required (archival tissue is acceptable if patient could not provide fresh or recent biopsy)
• ECOG performance status of 0 to 1
• Estimated life expectancy ≥3 months
• At least one measurable lesion by RECIST version 1.1
• Adequate hematologic function defined by white blood cell count ≥3 × 109/L with absolute neutrophil count ≥1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥100 × 109/L, and hemoglobin ≥9 g/dL (may have been transfused)
• Adequate hepatic function defined by a total bilirubin level ≤ the upper limit of normal range (ULN), an aspartate aminotransferase (AST) level ≤1.5 × ULN, and an alanine aminotransferase (ALT) level ≤1.5 × ULN
• Adequate renal function defined by an calculated creatinine clearance \> 30 mL/min according to the Cockcroft-Gault formula
• Both male and female subjects must be willing to use highly effective contraception (that is, methods with a failure rate of less than 1% per year) throughout the study and for at least 30 days after last avelumab treatment administration if the risk of conception exists (see section 6.1.7). \[NOTE: The effects of the study treatment on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use highly effective contraception, as stipulated in national or local guidelines. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the treating physician should be informed immediately.
• Signed written informed consent

You may not qualify if:

• Concurrent treatment with an anticancer treatment
• Prior therapy with any drug targeting T cell coregulatory proteins
• Major surgery for any reason within 4 weeks or if the patient had not fully recovered within 4 weeks
• Concurrent systemic therapy with corticosteroids or other immunosuppressive agents, or use of any investigational drug within 28 days before starting trial drug; short-term administration of systemic steroids (that is, for allergic reactions or the management of immune-mediated adverse events while on study is allowed
• Patients with active central nervous metastases will be excluded. Appropriately treated CNS metastases with either surgery or radiation therapy are permitted to participate in the study
• Prior organ transplantation, including allogenic stem-cell transplantation
• Known history of testing positive for HIV/AIDS, HBV, or HCV (including acute and chronic infection)
• Active or history of any autoimmune disease or immune-deficiencies (patients with type 1 diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible)
• Known monoclonal antibody hypersensitivity, history of anaphylaxis, or uncontrolled asthma
• Persisting toxicity related to prior therapy that was \> grade 1 according to NCI-CTCAE v4.0; grade ≤2 sensory neuropathy is allowed
• Pregnancy or lactation
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication All other significant diseases, which in the investigator's opinion may influence the patient's tolerance of trial treatment. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities 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
• Legal incapacity or limited legal capacity, including any psychiatric condition that would prohibit the understanding or rendering of informed consent
• Vaccination within 4 weeks of the first dose of Avelumab and while on study was prohibited except for administration of inactivated vaccines (e.g., inactivated influenza vaccines)

Sponsors & Collaborators

• Yousef Zakharia: lead
• Pfizer: collaborator
• University of Iowa: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Related Publications (1)

• Garje R, Ravindra A, Rahim B, Kroll M, Johnson JS, Torres J, Bonner J, Packiam VT, Mott S, O'Donnell M, Zakharia Y. Avelumab and taxol chemotherapy in platinum-refractory or ineligible metastatic urothelial carcinoma (AVETAX trial). Urol Oncol. 2025 Sep;43(9):520.e9-520.e18. doi: 10.1016/j.urolonc.2025.04.005. Epub 2025 May 31.

  PMID: 40451703 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

avelumab; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Yousef Zakharia, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: June 18, 2018
• First Posted: July 2, 2018
• Study Start: October 29, 2018
• Primary Completion: December 15, 2021
• Study Completion: February 9, 2024
• Last Updated: December 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)