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Thymic CarcinomaPhase 2RELEVENTNCT03921671

Ramucirumab and Carbo-Paclitaxel for Untreated Thymic Carcinoma / B3 Thymoma With Carcinoma (RELEVENT)

A Phase 2 study testing Ramucirumab in people with Thymic Carcinoma and Thymoma, run by Claudia Proto at 1 site in Italy.

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 The sponsor has not verified this record for over two years, so it may be out of date.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

This is a multicentric study. All patients with TET (thymic epithelial tumors) of any histological type will participate in the study. This is an open-label phase 2 study that will follow a Green-Dahlberg 2-stage design whose objective is to evaluate the activity and safety of the combination of ramucirumab (10 mg /… Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Thymic Carcinoma, Thymoma
What is being tested?
Ramucirumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteItaly
Study dates
1 Nov 2018to 16 Jul 2024
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 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • provision of written informed consent before treatment initiation
  • pathologically confirmed thymic carcinoma and B3 thymomas, with areas of carcinoma locally advanced as per central histological revision, recurrent and/or metastatic, not amenable to potentially curative treatments.
  • age>= 18 years old
  • provision of archival or fresh tissue (block or at least 15 charged slides 4μM of thickness).
  • Blood and plasma sampling at baseline and at first clinical revaluation
  • measurable disease (defined according to Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1);7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
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  • 8. adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1500/μL, haemoglobin
  • ≥9 g/dL (5.58 mmol/L), and platelets ≥100,000/μL; 9. adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy 10. adequate hepatic function as defined by a total bilirubin ≤1.5times the upper limit of normal (ULN), (Except for patients with Gilbert's syndrome who may only be included in the total bilirubin is < 3.0 x ULN or direct bilirubin < 1.5 x ULN) and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (or 5.0 times the ULN in the setting of liver metastases) 11. adequate renal function as defined by a serum creatinine ≤1.5 times the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is >1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed). The patient's urinary protein is
  • ≤1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥2+, a 24-hour urine collection for protein must demonstrate <1000 mg of protein in 24 hours to allow participation in this protocol).
  • 12. sexually active patients, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods). Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of protocol therapy. 13. Prior radiation therapy is allowed.
  • In case of chest radiotherapy a 28 days interval is needed between the end of the radiation treatment and the start of treatment .
  • In the case of focal or palliative radiation treatment a 7 days interval is needed from last radiation treatment to start of treatment (and provided that 25% or less of total bone marrow had been irradiated).
  • In the case of CNS radiation a minimum of 14 days interval is needed from the end of radiation treatment to start of treatment.

Who cannot join

  • previous systemic treatment for locally advanced/metastatic thymic carcinoma/B3 thymomas; patients treated in the neoadjuvant or adjuvant setting can be enrolled after discussion with PI
  • untreated CNS metastases. Patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least 2 weeks prior to start of treatment, or after surgical resection performed at least 28 days prior to start of treatment. The patient may have no evidence of Grade ≥1 CNS haemorrhage based on pre-treatment Magnetic Resonance Imaging (MRI) or IV contrast CT scan (performed within 28 days before start of treatment)
  • any Grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy
  • peripheral neuropathy ≥ G2History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy.
  • patient has experienced hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months prior to first dose of protocol therapy
  • radiographic evidence of intra-tumour cavitation, radiologically documented evidence of major blood vessel invasion or encasement by cancer
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  • history of uncontrolled hereditary or acquired thrombotic disorder
  • The patient has:
  • cirrhosis at a level of Child-Pugh B (or worse) or
  • cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
  • clinically relevant congestive heart failure (NYHA II-IV) or symptomatic or poorly controlled cardiac arrhythmia
  • The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy.uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management.
  • serious or no healing wound, ulcer, or bone fracture within 28 days prior to start of treatment
  • significant bleeding disorders, vasculitis, or experienced grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to start of treatment
  • history of GI perforation and / or fistulae within 6 months prior to start of treatment
  • bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhoea
  • peripheral neuropathy ≥grade 2 (NCI-CTCAE v 4.0)
  • serious illness or medical condition(s) including, but not limited to, the following: -Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)- related illness.
  • Active or uncontrolled clinically serious infection.
  • Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumours treated curatively and without evidence of recurrence for at least 3 years prior to start of treatment.
  • Uncontrolled metabolic disorders or other non-malignant organ or systemic diseases or secondary effects of cancer that induce a high medical risk and/or make assessment of survival uncertain.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient ineligible for entry into this study.
  • significant third-space fluid retention (for example, ascites or pleural effusion), and is not amenable for required repeated drainage
  • known allergy or hypersensitivity reaction to any of the treatment components
  • known history of active drug abuse
  • patient is pregnant or breastfeeding
  • major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy
  • elective or planned major surgery to be performed during the course of the clinical trial
  • patient is receiving concurrent treatment with other anticancer therapy
  • patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents.
  • Once-daily aspirin use (maximum dose 325 mg/day) is permitted.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan

Other trials in Italy

About this study

Official title: Improving Treatment Strategies in Thymic Epithelial Tumors: a TYME Collaborative Effort

This is a multicentric study. All patients with TET (thymic epithelial tumors) of any histological type will participate in the study. This is an open-label phase 2 study that will follow a Green-Dahlberg 2-stage design whose objective is to evaluate the activity and safety of the combination of ramucirumab (10 mg / kg) + carboplatin (AUC 5) and paclitaxel (200 mg / m2) in patients with relapsed and / or metastatic thymic carcinoma/ thymoma B3, in the first line (RELEVENT trial).

Read the detailed description

Clinical and quality of life data will be collected for all treated patient. Based on the histological evaluation performed by each participating center, patients will be screened for inclusion in one of the four studies, based on the following criteria:

  • TOPS study only: all patients with A, AB, B1, B2, B3 without areas of carcinoma histology, diagnosed during or after 2018, that do not have a fresh tissue sample and screen failures of the RELEVENT and BIOTET study;
  • TRY registry: all patients with TETs diagnosed, treated or followed from 2010 to 2017 included (retrospective data collection);
  • BIOTET only: all patients with A, AB, B1, B2, B3 without areas of histology of the carcinoma that have a fresh tissue sample;
  • RELEVENT only: all patients with thymoma B3 and areas of carcinoma and pa-tients with thymic carcinoma who do not have a fresh tissue sample.

Patients with thymic carcinoma or thymoma B3 with areas of carcinoma will receive a centralized pathological review of the tumour block or slides and will be screened to participate in the Phase II RELEVENT pharmacological study.Histological diagnosis will be confirmed before screening.

Being tested
Ramucirumab
Keywords
metastatic or relapsed non-pre-treated disease
Medical subject headings
Thymoma, Neoplasm Metastasis

What participants receive

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

  • RamucirumabCombination product

    Also called CARBOPLATIN (AUC 5) + PACLITAXEL(200 mg / m2)

    Combination of ramucirumab (10 mg / kg) + carboplatin (AUC 5) and paclitaxel (200 mg / m2) in patients with carcinoma thymic (or thymoma B3 with areas of carcinoma), relapsed and / or metastatic, in the first line.

Study groups in NCT03921671
Study groupRoleWhat they receive
Ramucirumab +carboplatin+ paclitaxelExperimentalAll patient will receive the combination of ramucirumab (10 mg / kg) + carboplatin (AUC 5) and paclitaxel (200 mg / m2) in patients with recurrent and / or metastatic thymic carcinoma or thymoma B3 with area of carcinoma, in the first line.
Receives: Combination Product: Ramucirumab

What is being measured

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

  1. Best tumour response (CR+PR)

    Objective tumor response will be assessed according to RECIST 1.1.

    Measured: 6 months

Secondary outcomes (3)

  1. Progression Free Survival (PFS)

    Disease progression will be established as the radiological progression according to RECIST 1.1 or through clinical assessment in case radiological evaluation is not feasible or as death from any cause due to clinical condition. PFS will be estimated through Kaplan-Meier method

    Measured: 4 years

  2. Overall Survival (OS)

    OS will be estimated through Kaplan-Meier method

    Measured: 4 years

  3. Safety

    AE/SAE will be reported and graded. Evaluaton of relationship with experimental drug will be done

    Measured: 4 years

Timeline

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

  1. First posted19 Apr 2019
  2. Study start1 Nov 2018
  3. Primary completion9 Oct 2021
  4. Study completion16 Jul 2024 (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
Model description
Green-Dahlberg 2-stage design
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03921671
Sponsor's protocol ID
NT-TET1-7371
Other IDs
2017-004494-13, 2017
Acronym
RELEVENT
Status last verified
Feb 2024
First submitted
22 Jun 2018
Last updated
29 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: hospital records; clinical and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, and correspondence. Data collection will be performed using electronic CRFs exclusively. No paper CRFs are provided to study investigators.

Publications

  • Benveniste MF, Korst RJ, Rajan A, Detterbeck FC, Marom EM; International Thymic Malignancy Interest Group. A practical guide from the International Thymic Malignancy Interest Group (ITMIG) regarding the radiographic assessment of treatment response of thymic epithelial tumors using modified RECIST criteria. J Thorac Oncol. 2014 Sep;9(9 Suppl 2):S119-24. doi: 10.1097/JTO.0000000000000296.

    PubMed 25396308

  • Berruti A, Borasio P, Gerbino A, Gorzegno G, Moschini T, Tampellini M, Ardissone F, Brizzi MP, Dolcetti A, Dogliotti L. Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience. Br J Cancer. 1999 Nov;81(5):841-5. doi: 10.1038/sj.bjc.6690773.

    PubMed 10555755

  • Enkner F, Pichlhofer B, Zaharie AT, Krunic M, Holper TM, Janik S, Moser B, Schlangen K, Neudert B, Walter K, Migschitz B, Mullauer L. Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets. Pathol Oncol Res. 2017 Jul;23(3):551-564. doi: 10.1007/s12253-016-0144-8. Epub 2016 Nov 14.

    PubMed 27844328

  • Garg RK. Posterior leukoencephalopathy syndrome. Postgrad Med J. 2001 Jan;77(903):24-8. doi: 10.1136/pmj.77.903.24.

    PubMed 11123390

  • Lopez-Garcia F, Amoros-Martinez F, Sempere AP. [A reversible posterior leukoencephalopathy syndrome]. Rev Neurol. 2004 Feb 1-15;38(3):261-6. Spanish.

    PubMed 14963856

  • Hirai F, Yamanaka T, Taguchi K, Daga H, Ono A, Tanaka K, Kogure Y, Shimizu J, Kimura T, Fukuoka J, Iwamoto Y, Sasaki H, Takeda K, Seto T, Ichinose Y, Nakagawa K, Nakanishi Y; West Japan Oncology Group. A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L. Ann Oncol. 2015 Feb;26(2):363-8. doi: 10.1093/annonc/mdu541. Epub 2014 Nov 17.

    PubMed 25403584

  • Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, Danso MA, Dennis K, Dupuis LL, Dusetzina SB, Eng C, Feyer PC, Jordan K, Noonan K, Sparacio D, Somerfield MR, Lyman GH. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017 Oct 1;35(28):3240-3261. doi: 10.1200/JCO.2017.74.4789. Epub 2017 Jul 31.

    PubMed 28759346

  • Lee VH, Wijdicks EF, Manno EM, Rabinstein AA. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Arch Neurol. 2008 Feb;65(2):205-10. doi: 10.1001/archneurol.2007.46.

    PubMed 18268188

  • Lemma GL, Lee JW, Aisner SC, Langer CJ, Tester WJ, Johnson DH, Loehrer PJ Sr. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol. 2011 May 20;29(15):2060-5. doi: 10.1200/JCO.2010.32.9607. Epub 2011 Apr 18.

    PubMed 21502559

  • Marinella MA, Markert RJ. Reversible posterior leucoencephalopathy syndrome associated with anticancer drugs. Intern Med J. 2009 Dec;39(12):826-34. doi: 10.1111/j.1445-5994.2008.01829.x. Epub 2008 Nov 3.

    PubMed 19220526

  • Okuma Y, Saito M, Hosomi Y, Sakuyama T, Okamura T. Key components of chemotherapy for thymic malignancies: a systematic review and pooled analysis for anthracycline-, carboplatin- or cisplatin-based chemotherapy. J Cancer Res Clin Oncol. 2015 Feb;141(2):323-31. doi: 10.1007/s00432-014-1800-6. Epub 2014 Aug 22.

    PubMed 25146529

  • Pagano M, Sierra NM, Panebianco M, Rossi G, Gnoni R, Bisagni G, Boni C. Sorafenib efficacy in thymic carcinomas seems not to require c-KIT or PDGFR-alpha mutations. Anticancer Res. 2014 Sep;34(9):5105-10.

    PubMed 25202099

  • Schwartz RB. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996 Jun 27;334(26):1743; author reply 1746. doi: 10.1056/NEJM199606273342613. No abstract available.

    PubMed 8637524

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ramucirumab in people with Thymic Carcinoma and Thymoma, run by Claudia Proto at 1 site in Italy.

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 13 inclusion and 31 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 29 May 2024. 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 Italy. 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?

Best tumour response (CR+PR) (time frame: 6 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 NCT03921671, which also lists 13 linked publications.

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 29 May 2024.

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