A Study Combining Eribulin Mesylate With Avelumab in Cisplatin Ineligible Metastatic Urothelial Cell Cancer Patients

NCT03502681 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: BTCRC-GU16-051
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single arm, open-label phase Ib study of combining eribulin mesylate with avelumab. The initial 9-12 patients (MTD cohort) will be enrolled to determine safety of avelumab in combination with eribulin mesylate. Upon determination of maximum tolerated dose (MTD), 12 additional patients will be enrolled in an expansion cohort (efficacy cohort) to determine ORR at 6 months.

Conditions

Metastatic Urothelial Cell Cancer

Keywords

Cisplatin-Ineligible; Avelumab; PD-L1 Monoclonal Antibody; Eribulin Mesylate

Outcome Measures

Primary Outcomes (2)

• Assess the Adverse Events of Combining Eribulin Mesylate With Avelumab - (MTD Cohort)

  Dose limiting toxicities (DLTs) experienced by subjects while being treated with the combination of eribulin+avelumab, by dose level.

  4-weeks

• Assess Response Rates (RR) - (Efficacy Cohort)

  Complete Response (CR) + Partial Response (PR)

  12 months

Secondary Outcomes (6)

• Assess Disease Control Rate (DCR)

  at 3, 6 months

• Estimate Progression Free Survival (PFS)

  12 months

• Estimate Overall Survival (OS)

  12 months

• Estimate Median Progression Free Survival (PFS)

  12 months

• Estimate Median Overall Survival (OS)

  2.5 years

Study Arms (1)

Maximum tolerated dose (MTD) cohort

EXPERIMENTAL

The initial 9-12 patients (MTD cohort) will be enrolled to determine safety of avelumab in combination with eribulin mesylate. Upon determination of maximum tolerated dose (MTD), 12 additional patients will be enrolled in an expansion cohort (efficacy cohort) to determine objective response rate (ORR) at 6 months.

Drug: Eribulin Mesylate; Drug: Avelumab

Interventions

Eribulin Mesylate DRUG

Days 1, 15 Eribulin mesylate: Dose level -1: 0.7mg/m\^2; Dose level 0: 1.1 mg/m\^2; Dose level +1: 1.4 mg/m\^2

Also known as: Halaven

Maximum tolerated dose (MTD) cohort

Avelumab DRUG

Days 1, 15 Avelumab (10mg/kg)

Also known as: MSB0010718C, BAVENCIO

Maximum tolerated dose (MTD) cohort

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2 at the time of enrollment.
• Life expectancy of \>12 weeks.
• Stage IV patients either locally advanced node positive (these patients must have N3 disease) or metastatic-M1 positive urothelial cancer of bladder and upper tract.
• Histologically proven urothelial carcinoma of bladder with predominant transitional cell component. Adenocarcinoma, squamous cell differentiation, or other atypical histology (such as plasmacytoid or sarcomotoid) of the bladder will be allowed on the study, provided they form \<50% of the histology.
• Presence of measurable disease per RECIST v1.1 for solid tumors.
• Patients who are cisplatin ineligible defined by the presence of one or more of the following:
• Impaired renal function (GFR ≥ 30 but ≤ 60 cc/min). GFR should be assessed by direct measurement (i.e. creatinine clearance or ethylenediaminetetra-acetate) or, if not available, by calculation from serum/plasma creatinine by Cockroft-Gault equation.
• Grade ≥ 2 Hearing Loss (hearing loss measured by audiometry of 25 dB at two contiguous frequencies)
• Grade ≥ 2 peripheral neuropathy (Please note that for enrollment on this trial patients must have peripheral neuropathy grade 2 or lower)
• ECOG Performance Status of 2
• NYHA Class III-IV CHF (Please note that for enrollment on this trial patients must have Ejection Fraction of \>35% measured on ECHO)
• Patients must be treatment naïve for metastatic disease. Use of chemotherapy in neoadjuvant or adjuvant form is allowed provided the time period between last dose of treatment and enrollment is \>12 months and subjects must have recovered from all reversible toxic effects of the regimen (other than alopecia) to ≤Grade 1 or baseline.
• Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to study registration:

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Participation in another clinical study with an investigational product within 2 weeks prior to registration.
• Any previous treatment with a PD1 or PD-L1 inhibitor, including Avelumab.
• Previous systemic immunotherapy. Previous use of intravesical BCG is acceptable.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence. However adequately treated prostate cancer \>3 years ago with no significant change in PSA for past 6 months can be included.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ.
• Receipt of the last dose of anti-cancer therapy for local recurrence only and not for any systemic disease (immunotherapy, endocrine therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigational agent) within14 days prior to study registration and within 6 weeks for intravesical BCG or mitomycin C .
• Mean QT interval corrected for heart rate (QTc) ≥470 ms on electrocardiogram (ECG) using Frediricia's Correction.
• Current or prior use of immunosuppressive medication within 28 days before study registration, with the exceptions of: a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) b) systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, c) steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Any unresolved toxicity (≥CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss). Alopecia, sensory neuropathy grade ≤ 2, or other grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
• Active or prior documented autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. NOTE: Subjects with diabetes type I, vitiligo, hypo- or hyperthyroid diseases, or psoriasis not requiring immunosuppressive systemic treatment are eligible. Patients with a history of completely resolved childhood asthma or atopy are also eligible.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of and/or confirmed pneumonitis.

Sponsors & Collaborators

• Monika Joshi, MD: lead
• Pfizer: collaborator
• Eisai Inc.: collaborator
• Big Ten Cancer Research Consortium: collaborator

Study Sites (2)

Univeristy of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

Penn State Cancer Intsitute

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (1)

• Joshi M, Holder SL, Zhu J, Zheng H, Komanduri S, Warrick J, Yasin H, Garje R, Jia B, Drabick JJ, DeGraff DJ, Zakharia Y. Avelumab in Combination with Eribulin Mesylate in Metastatic Urothelial Carcinoma: BTCRC GU-051, a Phase 1b Study. Eur Urol Focus. 2022 Mar;8(2):483-490. doi: 10.1016/j.euf.2021.03.005. Epub 2021 Mar 17.

  PMID: 33741296 DERIVED

Related Links

• Big Ten Cancer Research Consortium Website

MeSH Terms

Interventions

eribulin; avelumab

Limitations and Caveats

Due to the early termination of the study, no primary or secondary endpoints were analyzed.

Results Point of Contact

• Title: Clinicaltrials.gov Results Coordinator
• Organization: Hoosier Cancer Research Network

jsmith@hoosiercancer.org

317-921-2050

Study Officials

• Monika Joshi, M.D.

  Big Ten Cancer Research Consortium

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: Sponsor-Investigator

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: April 19, 2018
• Study Start: June 12, 2018
• Primary Completion: October 25, 2019
• Study Completion: October 25, 2019
• Last Updated: July 1, 2022
• Results First Posted: July 9, 2020

Record last verified: 2022-06

Locations

US (2)