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Neuroendocrine CarcinomasPhase 2NCT02695459

Cisplatinum and Everolimus in Patients With Metastatic or Unresectable NEC of Extrapulmonary Origin

A Phase 2 study testing cisplatinum and everolimus in people with Neuroendocrine Carcinomas, run by The Netherlands Cancer Institute at 3 sites in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Phase II, open-label, multicentre national study. Patients with metastatic neuroendocrine carcinomas of extrapulmonary origin will be eligible. Treatment will be performed as indicated in the section "Investigational drug and reference therapy". Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Carcinomas
What is being tested?
cisplatinum and everolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
3 sitesNetherlands
Study dates
30 Mar 2016to Aug 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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Pathologically confirmed unresectable locally advanced and/or metastatic NEC of extrapulmonary origin (WHO 2010 classification; Ki67 >20 %) where no curative (chemoradiation) treatment options are available(including merkel cell carcinoma).
  • Measurable disease according to RECIST 1.1, on CT-scan or MRI
  • ECOG Performance status 0-2 (see Appendix 2)
  • Adequate bone marrow function as shown by: ANC≥1.5 x 109/L, Platelets ≥100 x 109/L, Hb >6 mmol/L
  • Adequate liver function as shown by:
  • Total serum bilirubin ≤1.5 ULN
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  • ALT and AST ≤2.5x ULN (≤5x ULN in patients with liver metastases)
  • Adequate renal function: calculated creatinin clearance > 60ml/min. (Cockcroft-Gault formula)
  • Life expectancy of at least 3 months.
  • Male or female age ≥ 18 years.
  • Signed informed consent.
  • Able to swallow and retain oral medication.
  • Locally advanced or metastatic lesion(s) of which a histological biopsy can safely be obtained:
  • Patients with safely accessible locally advanced or metastatic lesion(s) including bone lesions.
  • Patients not known with bleeding disorders (such as hemophilia) or bleeding complications from biopsies, dental procedures or surgeries.
  • Patients not using any anti-coagulant medication at the time of biopsy: all aspirin derivatives, NSAID's, coumarines, platelet function inhibitors, heparins (including LMWHs) and oral factor Xa inhibitors are not allowed, unless medication can either be safely stopped or counteracted.
  • Adequate coagulation status as measured by:
  • PT < 1.5 x ULN or PT-INR < 1.5
  • APTT < 1.5 x ULN
  • On the day of biopsy in patients using coumarines: PT-INR < 1.5
  • Patients not known with contraindications for lidocaine (or its derivatives)

Who cannot join

  • Previous chemotherapy for metastatic or unresectable NEC of extrapulmonary origin. (prior peri-operative chemotherapy or chemoradiation for curative intention is allowed if at least 6 months have elapsed between completion of this therapy and enrolment into the study).
  • Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus, everolimus)
  • Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma.
  • Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) or cisplatinum
  • Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
  • Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary
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  • Patients who have any severe and/or uncontrolled medical conditions such as: a. unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to randomization, serious uncontrolled cardiac arrhythmia and poorly controlled hypertension (systolic BP >180 mmHg or diastolic BP >100 mmHg);. b. active or uncontrolled severe infection, c. liver disease such as cirrhosis, decompensated liver disease, and known history chronic hepatitis d. known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air), e. active, bleeding diathesis;
  • Chronic treatment with corticosteroids or other immunosuppressive agents
  • Known history of HIV seropositivity
  • Pregnant or nursing (lactating) women
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 6 months after stopping study treatment.
  • Sexually active males, unless they use a condom during intercourse while taking study medication and for 6 months after stopping study medication.
  • Patients with dyspnoea at rest due to complications of advanced malignancy or other disease, or who require supportive oxygen therapy.
  • History or clinical evidence of brain metastases.
  • Any investigational drug treatment within 4 weeks of start of study treatment.
  • Radiotherapy within 4 weeks of start of study treatment (2 week interval allowed if palliative radiotherapy given to bone metastatic site peripherally and patient recovered from any acute toxicity).

Trial locations and contacts

3 sites in 1 country.

Netherlands3 sites

  • NKI-AVL

    Amsterdam, 1066CX

  • UMCG

    Groningen

  • Erasmus Medisch Centrum

    Rotterdam

Other trials in Netherlands

About this study

Official title: Phase II Study of Cisplatinum and Everolimus in Patients With Metastatic or Unresectable Neuroendocrine Carcinomas (NEC) of Extrapulmonary Origin

Phase II, open-label, multicentre national study. Patients with metastatic neuroendocrine carcinomas of extrapulmonary origin will be eligible. Treatment will be performed as indicated in the section "Investigational drug and reference therapy". Cisplatinum and everolimus dosing is based upon earlier phase 1 studies (Fury et al. 2012). CTs will be done at 9 weekly intervals (after 3 courses of chemotherapy;). Patients will be treated until documented progression according to RECIST 1.1. Enrolment is expected to take between 14 - 16 months. The total study duration is estimated to be 2 to 3 years until publication. Three NET centres in The Netherlands will participate, (Erasmus Medical Center in Rotterdam, Netherlands Cancer Institute in Amsterdam and , the University Medical Center of Groningen) A pre-treatment (and optional post-treatment) tumour biopsy will be included for DNA/RNA analyses and organoid culture. An additional 5cc of blood will be withdrawn as a germline DNA reference. A second 5 cc of blood will be included for measuring circulating tumour transcripts to identify all types of GEP-NET (NETTest).

Being tested
cisplatinum and everolimus
Medical subject headings
Carcinoma, Neuroendocrine

What participants receive

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

  • cisplatinum and everolimusDrug

    Also called cisplatinum, everolimus

    Cisplatinum : 75 mg/m2 days 1,iv Everolimus : 7.5 mg daily: days 1-21 orally

Study groups in NCT02695459
Study groupRoleWhat they receive
cisplatinum and everolimusExperimentalCisplatinum : 75 mg/m2 days 1,iv Everolimus : 7.5 mg daily: days 1-21 orally
Receives: Drug: cisplatinum and everolimus

What is being measured

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

  1. disease control rate

    patients having a complete response, partial response or stable disease are considered successes

    Measured: every 9 weeks until up to 16 months

Secondary outcomes (4)

  1. time to relapse

    Measured: From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

  2. overall survival

    Measured: Time from registration until the date of death from any cause, assessed up to 60 months

  3. Effect on the markers chromogranin A (CgA) and neuron-specific enolase (NSE);

    Measured: from registration in the study markers will be taken every cycle until a maximum of 6 cycles is reached (cycle is every 3 weeks), until a maximum of 18 weeks.

  4. Safety of everolimus in combination with cisplatin (AEs according to CTCAE v4.0)

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

    Measured: up to 30 days after end of treatment

Timeline

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

  1. First posted1 Mar 2016 (estimated)
  2. Study start30 Mar 2016
  3. Primary completionApr 2021
  4. Study completionAug 2021 (estimated)

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
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02695459
Sponsor's protocol ID
M14NEC
Status last verified
Apr 2021
First submitted
18 Feb 2016
Last updated
20 Apr 2021
Results posted
No
Data monitoring committee
No

Publications

  • Levy S, Verbeek WHM, Eskens FALM, van den Berg JG, de Groot DJA, van Leerdam ME, Tesselaar MET. First-line everolimus and cisplatin in patients with advanced extrapulmonary neuroendocrine carcinoma: a nationwide phase 2 single-arm clinical trial. Ther Adv Med Oncol. 2022 Feb 27;14:17588359221077088. doi: 10.1177/17588359221077088. eCollection 2022.

    PubMed 35251315

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cisplatinum and everolimus in people with Neuroendocrine Carcinomas, run by The Netherlands Cancer Institute at 3 sites in Netherlands.

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 21 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 20 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Netherlands. 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?

Results are not available in the source record.

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?

disease control rate (time frame: every 9 weeks until up to 16 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 NCT02695459, 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 20 Apr 2021.

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