Study of Gemcitabine, Carboplatin and VELIPARIB (ABT-888) in Refractory Testicular Germ Cell Cancer

NCT02860819 | Completed Phase 2

• 1 other identifier: GCTSK004
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a proof-of-concept study to define efficacy of gemcitabine, carboplatin and VELIPARIB (ABT-888) in patients with refractory germ cell tumors (GCTs). PARP proteins are involved in base excision repair (BER), one of the major DNA repair system in cells and PARP is overexpressed in testicular GCTs (TGCTs) compared to normal testis and data suggest that PARP overexpression is early event in TGCTs development. Patients with low PARP expression in primary tumour had non-significantly better OS compared to patients with high PARP expression (5-year OS 89.2% vs 78.7%; HR=0.50, 95% CI 0.21 to 1.17, p=0.12). The aim of this study is to evaluate PARP inhibitor VELIPARIB in combination with gemcitabine, carboplatin in patients with refractory germ cell tumors (GCTs).

Conditions

Testicular Cancer

Keywords

Multiple relapsed/refractory testicular germ cell tumors; PARP inhibition; Chemotherapy; Gemcitabine; Carboplatin

Outcome Measures

Primary Outcomes (1)

• Percentage of patients that will be free of disease progression according to RECIST criteria 12-months after the first administration of the treatment.

  Percentage of patients that will be free of disease progression according to RECIST criteria 12-months after the first administration of the treatment.

  12-months

Secondary Outcomes (4)

• Response rate

  6-weeks

• Median overall survival

  12 months

• Median progression-free survival

  12-months

• Frequency of grade III and IV adverse events

  3-weeks

Study Arms (1)

Gemcitabine, Carboplatin, Veliparib

EXPERIMENTAL

Gemcitabine 800mg/m2 day 1 and 8 every 3 weeks; Carboplatin AUC = 4, day 1, every 3 weeks, Veliparib 250mg bid day continuously.

Drug: Veliparib; Drug: Gemcitabine; Drug: Carboplatin

Interventions

Veliparib DRUG

Veliparib 250mg BID, continuously

Also known as: ABT-888

Gemcitabine, Carboplatin, Veliparib

Gemcitabine DRUG

Gemcitabine 800mg/m2, day 1 and 8

Gemcitabine, Carboplatin, Veliparib

Carboplatin DRUG

Carboplatin AUC = 4, day 1

Gemcitabine, Carboplatin, Veliparib

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,
• Measurable disease radiologically
• 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 \< 3 ULN or \< 5 in case of liver metastases. For subjects with Gilbert's syndrome bilirubin \> 1.5 × ULN is allowed if no symptoms of compromised liver function are present
• Adequate renal function: measured or calculated (by Cockcroft formula) creatinine clearance \> 50 ml/min. Cockcroft formula: CLcr = \[(140-age) x weight(Kg)\]/\[72 x creatinine (mg/dl)\]
• 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 nonmelanoma skin cancer
• Prior PARP1 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)
• Patients with other severe acute or chronic medical condition, or laboratory abnormality that would impair, in the judgment of investigator, excess risk associated with study treatment, or which, in judgment of the investigator, would make the patient inappropriate for entry into this study
• Inability of oral intake, or drug absorption (e.g. malabsorption syndrome)
• 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
• Patients with history of or current CNS metastasis
• Patients with history of seizures

Sponsors & Collaborators

• National Cancer Institute, Slovakia: lead

Study Sites (1)

National Cancer Institute

Bratislava, 83310, Slovakia

Location

Related Publications (1)

• Mego M, Svetlovska D, Reckova M, Angelis D, Kalavska K, Obertova J, Palacka P, Rejlekova K, Sycova-Mila Z, Chovanec M, Mardiak J. Gemcitabine, carboplatin and veliparib in multiple relapsed/refractory germ cell tumours: The GCT-SK-004 phase II trial. Invest New Drugs. 2021 Dec;39(6):1664-1670. doi: 10.1007/s10637-021-01130-5. Epub 2021 May 29.

  PMID: 34052929 DERIVED

MeSH Terms

Conditions

Testicular Neoplasms

Interventions

veliparib; Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Michal Mego, Assoc.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

Study Record Dates

• First Submitted: July 14, 2016
• First Posted: August 9, 2016
• Study Start: August 1, 2016
• Primary Completion: November 30, 2020
• Study Completion: February 15, 2021
• Last Updated: March 3, 2021

Record last verified: 2020-12

Locations

SL (1)