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

NCT03921671 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: NT-TET1-73712017-004494-13
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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 / 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).

Conditions

Thymic Carcinoma; Thymoma

Keywords

metastatic or relapsed non-pre-treated disease

Outcome Measures

Primary Outcomes (1)

• Best tumour response (CR+PR)

  Objective tumor response will be assessed according to RECIST 1.1.

  6 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  4 years

• Overall Survival (OS)

  4 years

• Safety

  4 years

Other Outcomes (4)

• Comprehensive analysis of tumor mutational status on paraffin-embedded tissue

  4 years

• Comprehensive analysis of single nucleotide polymorphism in blood

  4 years

• Analysis of circulating micro-RNA

  4 years

Study Arms (1)

Ramucirumab +carboplatin+ paclitaxel

EXPERIMENTAL

All 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.

Combination Product: Ramucirumab

Interventions

Ramucirumab COMBINATION_PRODUCT

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.

Also known as: CARBOPLATIN (AUC 5) + PACLITAXEL(200 mg / m2)

Ramucirumab +carboplatin+ paclitaxel

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• \. 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).
• \. 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Claudia Proto: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Related Publications (13)

• 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.

  PMID: 25396308 RESULT

• 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.

  PMID: 10555755 RESULT

• 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.

  PMID: 27844328 RESULT

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

  PMID: 11123390 RESULT

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

  PMID: 14963856 RESULT

• 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.

  PMID: 25403584 RESULT

• 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.

  PMID: 28759346 RESULT

• 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.

  PMID: 18268188 RESULT

• 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.

  PMID: 21502559 RESULT

• 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.

  PMID: 19220526 RESULT

• 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.

  PMID: 25146529 RESULT

• 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.

  PMID: 25202099 RESULT

• 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.

  PMID: 8637524 RESULT

MeSH Terms

Conditions

Thymoma; Neoplasm Metastasis

Interventions

Ramucirumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Thymus Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Marina Garassino, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Green-Dahlberg 2-stage design

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: April 19, 2019
• Study Start: November 1, 2018
• Primary Completion: October 9, 2021
• Study Completion: July 16, 2024
• Last Updated: May 29, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: From the first patient enrolled, to the end of the study
• Access Criteria: Direct access to source data will be granted to authorised representatives from the Sponsor, host institution and the regulatory authorities to permit trial-related monitoring, audits and inspections. Access to the study clinical data entry platform will be granted to trial staff through a computer-based credential generation system in the following manner:

Locations

IT (1)