Avelumab in Refractory Testicular Germ Cell Cancer.

NCT03403777 | Completed Phase 2

• 1 other identifier: NCISlovakia
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a proof-of-concept study to define efficacy of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). Data suggest that PD-L1 is overexpressed in TGCTs, and PD-L1 expression is significantly higher in GCTs in comparison to normal testicular tissue.Patients with low PD-L1 expression had significantly better progression-free survival (hazard ratio \[HR\] = 0.40, 95% CI (0.16 - 1.01, p = 0.008) and overall survival (HR = 0.43, 95% CI (0.15 - 1.23, p = 0.040) compared to patients with high PD-L1 expression. These data suggest that PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs and that there is strong rationale to inhibit PD-1/PD-L1 signaling in GCTs.

Conditions

Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms; Testicular Diseases; Gonadal Disorders; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action

Keywords

Multiple relapsed/refractory testicular germ cell tumors; Avelumab; Anti PD-L1

Outcome Measures

Primary Outcomes (1)

• To determine the efficacy (as measured by 12-week progression-free survival) of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs).

  12-week progression-free survival

  12-weeks

Secondary Outcomes (3)

• To describe the favorable response rate of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs).

  4-weeks

• Progression-free survival (PFS) of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs).

  12-months

• Toxic effects of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs).

  12-weeks

Study Arms (1)

Avelumab

EXPERIMENTAL

AVELUMAB will be administered intravenously 10mg/kg every 2 weeks. Courses will be repeated every 14 days until progression or unacceptable toxicity. AVELUMAB will be administered as a 1-hour (-10 minutes / +20 minutes, i.e., 50-80 minutes) intravenous (i.v.) infusion. The dose of AVELUMAB will be calculated based on the weight of the subject determined on the day prior to or the day of each drug administration.

Drug: Avelumab

Interventions

Avelumab DRUG

AVELUMAB will be administered intravenously 10mg/kg every 2 weeks.

Also known as: Bavencio

Avelumab

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent
• Men aged 18 years or older
• ECOG performance status: 0-1
• Histologically confirmed extracranial primary germ cell cancer, seminoma, or nonseminoma
• Rising serum markers (i.e., alpha-fetoprotein and human chorionic gonadotropin) on sequential measurement or biopsy-proven unresectable germ cell cancer
• Refractory GCTs e.g. patients relapsing after high-dose chemotherapy or for patients non fit enough for high-dose chemotherapy
• Primary mediastinal GCTs in first relapse
• Patient's disease must not be amenable to cure with either surgery or chemotherapy in the opinion of investigator,
• RECIST 1.1 Measurable disease
• Adequate hematologic function defined by ANC ≥ 1500/mm3, platelet count ≥ 100 000/mm3 and hemoglobin level ≥ 9g/dl.
• Adequate liver function defined by a total bilirubin level ≤ 1.5 ULN, and ALT, AST ≤ 2.5 × ULN . or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
• Adequate renal function: measured or calculated (by Cockcroft formula) creatinine clearance ≥ 30 ml/min. Cockcroft formula: CLcr = \[(140-age) x weight(Kg)\]/\[72 x creat (mg/dl)\]
• At least 4 weeks must have elapsed since the last radiotherapy and/or chemotherapy before study entry,
• At least 4 weeks must have elapsed since the last major surgery
• Complete recovery from prior surgery, and/or reduction of all adverse events from previous systemic therapy or radiotherapy to grade 1,

You may not qualify if:

• Other prior malignancy except successfully treated non-melanoma skin cancer
• No prior PD-1/PD-L1 inhibitor
• Other concurrent approved or investigational anticancer treatment, including surgery, radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or immunotherapy
• Female patients
• Patients infected by the Human Immunodeficiency Virus (HIV)
• 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.
• Other significant diseases: e.g. immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; Patients with other severe acute or chronic medical condition, or laboratory abnormality that would impair, in the judgment of investigator, excess risk associated with the study participation, study treatment administration, or may interfere with the interpretation of study results and, which, in judgment of the investigator, would make the patient inappropriate for entry into this study.
• Hypersensitivity to any compound of the drug
• Sexually active men not using highly effective birth control if their partners are women of child-bearing potential
• All subjects with brain metastases, except those meeting the following criteria:
• Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment
• No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
• Subjects must be either off steroids or on a stable or decreasing dose of \<10mg daily prednisone (or equivalent)
• Prior organ transplantation, including allogeneic stem cell transplantation
• Significant acute or chronic infections including, among others:

Sponsors & Collaborators

• National Cancer Institute, Slovakia: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

National Cancer Institute

Bratislava, 83310, Slovakia

Location

Related Publications (1)

• 1) Broun ER et al. Ann Intern Med 1993; 117: 124-8 2) Cierna et al., Ann Oncol, Ann Oncol. 2016 Feb;27(2):300-5. 3) Feldman et al Cancer 2012;118:981-6. 4) Horwich A, et al. Lancet 2006; 367: 754-65 5) Kollmannsberger C et al. Cancer 2006; 106: 1217-26 6) Kondagunta GV et al. J Clin Oncol. 2005 23:6549-55. 7) Mardiak J et al. Neoplasma, 2005; 52: 497-501 8) Fankhauser, C. D et al. Br J Cancer. 2015, 113: 411-413 9) Heery et al. J Clin Oncol 33, 2015 (suppl; abstr 3055) 10) Yamada et al. J Clin Oncol 33, 2015 (suppl; abstr 4047) 11) Disis et al. J Clin Oncol 33, 2015 (suppl; abstr 5509) 12) Gulley et al. J Clin Oncol 33, 2015 (suppl; abstr 8034) 13) Shitara K et al. J Clin Oncol 33, 2015 (suppl; abstr 3023) 14) Kelly K et al. J Clin Oncol 33, 2015 (suppl; abstr 3044) 15) Boyerinas B et al. Cancer Immunol Res. 2015 Oct;3(10):1148-57.

  BACKGROUND

MeSH Terms

Conditions

Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms; Testicular Diseases; Gonadal Disorders

Interventions

avelumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Neoplasms by Histologic Type

Study Officials

• Michal Mego, prof

  National Cancer Institute (NCI)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Non-randomized, open-label, multi-centre trial to assess efficacy (as measured by 12-week progression-free survival) of AVELUMAB in patients with refractory germ cell tumors (GCTs). The Simon optimal 2-stage design (see statistical section) will be used. See section 6 (Statistical Considerations) for specific details.

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 19, 2018
• Study Start: November 15, 2017
• Primary Completion: February 28, 2019
• Study Completion: February 28, 2019
• Last Updated: March 5, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)