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Testicular CancerPhase 2NCT02860819

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

A Phase 2 study testing Veliparib, Gemcitabine and Carboplatin in people with Testicular Cancer, run by National Cancer Institute, Slovakia at 1 site in Slovakia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Testicular Cancer
What is being tested?
Veliparib, Gemcitabine and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteSlovakia
Study dates
1 Aug 2016to 15 Feb 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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,
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Who cannot join

  • Patients who do not fit inclusion criteria
  • 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)
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  • 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

Trial locations and contacts

1 site in 1 country.

Slovakia1 site

  • National Cancer Institute

    Bratislava, 83310

Other trials in Slovakia

About this study

Official title: Phase II Study of Gemcitabine, Carboplatin and VELIPARIB (ABT-888) in Refractory Testicular Germ Cell Cancer

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).

Read the detailed description

PARP proteins are involved in base excision repair (BER), one of the major DNA repair system in cells. Recently, it was showed that PARP inhibitors have striking efficacy in patients with BRCA1 deficient or triple negative breast cancer in monotherapy or in combination with cisplatin based chemotherapy, without increased systemic toxicity. Pertubations affecting homologous recombination (HR) involved in DNA repair are associated with higher probability of response to PARP inhibitors. Inactivation of PTEN, tumor suppressor protein, is associated with defects in HR and response to PARP inhibitors.

Recently, PARP expression was evaluated in TGCTs. It was showed that PARP is overexpressed in testicular germ cell tumours compared to normal testis and 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).Loss of the tumor suppressor gene PTEN marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive germ cell tumors. In the testis, PTEN was abundantly expressed in germ cells whereas it was virtually absent from 56% of seminomas as well as from 86% of embryonal carcinomas and virtually all teratomas. On the contrary, ITGCN intensely expressed PTEN, indicating that loss of PTEN expression is not in early event in testicular tumor development, but is associated with progression of disease. Previously, it was showed, that testicular germ cell tumors cell lines have low activity of proteins involved in nuclear excision repair (NER) and it is assumed that low NER activity is related to the favorable response of testis tumors to cisplatin-based chemotherapy.

Gemcitabine and carboplatin showed activity in refractory TGCTs. Recently, maximal tolerated dose of Veliparib (ABT-888) with gemcitabine and carboplatin was established.

Based on aforementioned data, there is strong rationale to inhibit PARP in TGCT. Inactivation of PARP by Veliparib along with defects of homologous recombination due to PTEN inactivation in GCTs and low activity of nucleotide excision repair system will dramatically increase antitumor effect gemcitabine and carboplatin in patients with progressing or relapsing germ cell cancer.

Being tested
Veliparib, Gemcitabine, Carboplatin
Keywords
Multiple relapsed/refractory testicular germ cell tumors, PARP inhibition, Chemotherapy, Gemcitabine, Carboplatin
Medical subject headings
Testicular Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VeliparibDrug

    Also called ABT-888

    Veliparib 250mg BID, continuously

  • GemcitabineDrug

    Gemcitabine 800mg/m2, day 1 and 8

  • CarboplatinDrug

    Carboplatin AUC = 4, day 1

Study groups in NCT02860819
Study groupRoleWhat they receive
Gemcitabine, Carboplatin, VeliparibExperimentalGemcitabine 800mg/m2 day 1 and 8 every 3 weeks; Carboplatin AUC = 4, day 1, every 3 weeks, Veliparib 250mg bid day continuously.
Receives: Drug: Veliparib; Drug: Gemcitabine; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12-months

Secondary outcomes (4)

  1. Response rate

    Response rate as measured by RECIST 1.1

    Measured: 6-weeks

  2. Median overall survival

    Median overall survival. Overall survival will be measured from the date of first administration of the treatment until death or date of last follow-up.

    Measured: 12 months

  3. Median progression-free survival

    Median progression-free survival. Progression-free survival will be measured from the date of first administration of the treatment until progression, death or date of last follow-up.

    Measured: 12-months

  4. Frequency of grade III and IV adverse events

    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measured: 3-weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2016 (estimated)
  2. Study start1 Aug 2016
  3. Primary completion30 Nov 2020
  4. Study completion15 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02860819
Sponsor's protocol ID
GCTSK004
Status last verified
Dec 2020
First submitted
14 Jul 2016
Last updated
3 Mar 2021
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 34052929

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Veliparib, Gemcitabine and Carboplatin in people with Testicular Cancer, run by National Cancer Institute, Slovakia at 1 site in Slovakia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Slovakia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients that will be free of disease progression according to RECIST criteria 12-months after the first administration of the treatment. (time frame: 12-months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02860819, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2021.

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