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MesotheliomaPhase 2RAMESNCT03560973

A Double Blind, Placebo Controlled, Randomized Phase II Study Evaluating Gemcitabine With or Without Ramucirumab , for II Line Treatment MPM

A Phase 2 study testing Gemcitabine and Ramucirumab in people with Mesothelioma, run by Gruppo Oncologico Italiano di Ricerca Clinica at 1 site in Italy.

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

Study RAMES is a multicentre, double-blind, randomized Phase II study exploring the efficacy and evaluating the safety of the addition of ramucirumab to gemcitabine as the second-line treatment of patients with diffuse pleural mesothelioma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mesothelioma
What is being tested?
Gemcitabine and Ramucirumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
164 participants
Where
1 siteItaly
Study dates
22 Dec 2016to 20 Jul 2022
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

  • The patient has a histopathologically or cytologically confirmed diagnosis of malignant pleural mesothelioma.
  • The patient has documented disease progression after the last dose of first-line chemotherapy for metastatic disease,
  • Patients who are intolerant to first-line chemotherapy regimens are eligible. Disease progression must be assessed after the last dose of first-line therapy.
  • The patient received combination chemotherapy prior to disease progression.
  • Prior chemotherapy regimens must include a platinum or pemetrexed component. Exposure to antineoplastic therapy, in addition to platinum and/or pemetrexed, is acceptable if the agents were used in the first-line metastatic or neoadjuvant/adjuvant setting.
  • Patients who have had one or more components of first-line chemotherapy discontinued because of toxicity, but continued to receive the other component(s), are eligible following disease progression.
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  • The patient has metastatic disease or locally advanced disease that is measurable, or nonmeasurable but evaluable, by radiological imaging per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) (Eisenhauer et al. 2009 Baseline tumor assessment should be performed using a high resolution computed tomography (CT) scan using intravenous and oral contrast unless clinically contraindicated. Magnetic resonance imaging (MRI) is acceptable if a CT cannot be performed.
  • The patient has an ECOG performance status of 0-2
  • The patient has adequate organ function.
  • The patient is at least 18 years old or of an acceptable age according to local regulations, whichever is older.
  • The patient has provided written informed consent prior to any study-specific procedures and is amenable to compliance with protocol schedules and testing.
  • The patient has an estimated life expectancy of 12 weeks in the judgment of the investigator.
  • The patient has resolution to Grade 1 by Common Terminology Criteria for Adverse Events CTCAE Version 4 NCI 2009, of all clinically significant toxic effects of previous anticancer therapy.
  • The patient, if male, is sterile (including vasectomy confirmed by post-vasectomy semen analysis) or agrees to use a reliable method of birth control and to not donate sperm during the study and for at least 12 weeks following the last dose of study treatment.
  • The patient, if female, is surgically sterile, is postmenopausal, or agrees to use a highly effective method of birth control during the study and for 12 weeks following the last dose of study treatment. A highly effective method of birth control is defined as one that results in a low failure rate when used consistently and correctly.
  • The patient, if female and of child-bearing potential, must have a negative serum or urine pregnancy test within 7 days prior to randomization.

Who cannot join

  • The patient has cancer with histology other than mesothelioma.
  • The patient is receiving chronic therapy with any of the following within 7 days prior to randomization:
  • nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents)
  • other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide) Aspirin use at doses up to 325 mg/day is permitted.
  • The patient received radiotherapy within 14 days prior to randomization. Any lesion requiring palliative radiotherapy or which has been previously irradiated cannot be considered for response assessment.
  • The patient received >1 line of prior therapy for the treatment MPM.
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  • The patient received previous treatment with agents targeting the VEGF/VEGF Receptor 2 signaling pathway, including previous exposure to ramucirumab.
  • The patient has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression. Screening of asymptomatic patients is not required.
  • The patient has a significant bleeding disorder or vasculitis or had a Grade 3 bleeding episode within 12 weeks prior to randomization.
  • The patient experienced any arterial thromboembolic event (ATE), including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
  • The patient has symptomatic congestive heart failure (CHF; New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
  • The patient has uncontrolled hypertension, as defined in CTCAE Version 4.0, prior to initiating study treatment, despite antihypertensive intervention. CTCAE Version 4.0 defines uncontrolled hypertension as Grade >2 hypertension; clinically, the patient continues to experience elevated blood pressure (systolic >160 mmHg and/or diastolic >100 mmHg) despite medications).
  • The patient underwent major surgery within 28 days prior to randomization or central venous access device placement within 7 days prior to randomization. The patient has a serious or nonhealing wound, ulcer or bone fracture within 28 days prior to enrollment.
  • The patient has selective or planned major surgery to be performed during the course of clinical trial.
  • The patient has a history of gastrointestinal (GI) perforation or fistula within 6 months prior to randomization.
  • The patient has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) 12 months prior to randomization.
  • The patient has an acute or subacute bowel obstruction or history of chronic diarrhoea that is considered clinically significant in the opinion of the investigator.
  • The patient has either of the following:
  • cirrhosis at a level of Child-Pugh B (or worse)
  • cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis.
  • The patient has known allergy or hypersensitivity to any components of study treatment.
  • The patient received any previous investigational therapy within 4 half -lives of the investigational agent prior to randomization.
  • The patient has a serious illness or medical condition including, but not limited to, the following:
  • known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
  • active or uncontrolled clinically serious infection
  • The patient is pregnant or breast-feeding.
  • The patient has a concurrent active malignancy other than the following:
  • adequately treated not melanomatous skin cancer
  • curatively treated in situ carcinoma of the cervix or other not invasive carcinoma or in situ neoplasm A patient with a history of prior malignancy is eligible if he or she has been disease free for 3 years prior to randomization.
  • The patient has a serious nonhealing: (a) wound, (b) peptic ulcer, or (c) bone fracture, within 28 days prior to randomization.
  • The patient experienced any Grade 3 or 4 venous thromboembolic event (VTE) that is considered by the investigator to be life-threatening or that is symptomatic and not adequately treated by anticoagulation therapy, within 6 months prior to randomization (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant")
  • The patient has any condition (for example, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggests that the patient is, in the investigator's opinion, not an appropriate candidate for the study.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Struttura Complessa di OncologiaIRCCS- Istituto in Tecnologie Avanzate e Modelli Assistenziali in Oncologia Arcispedale Santa Maria Nuova

    Reggio Emilia, 42123

Other trials in Italy

About this study

Official title: A Double-blind, Placebo Controlled, Randomized Multicenter Phase II Study Evaluating Gemcitabine With or Without Ramucirumab as II Line Treatment for Advanced Malignant Pleural Mesothelioma

Study RAMES is a multicentre, double-blind, randomized Phase II study exploring the efficacy and evaluating the safety of the addition of ramucirumab to gemcitabine as the second-line treatment of patients with diffuse pleural mesothelioma. Patients will be randomly assigned (1:1) to receive intravenous gemcitabine 1000 mg/m2 on days 1 and 8 every 21 days with placebo or combined with intravenous ramucirumab 10 mg/Kg (ramucirumab group) on day 1 of a 21 day cycle until PD. Randomisation will be done via a centralized system and will stratified by performance status (0-1 vs 2), age (≤70 vs >70), histology (epithelioid vs others), time to progression (TTP) after a previous treatment (first line therapy, adjuvant or neoadjuvant therapy) (< 6 months vs ≥6 months).

Conditions
Mesothelioma
Being tested
Gemcitabine, Ramucirumab
Medical subject headings
Mesothelioma

What participants receive

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

  • GemcitabineDrug

    Also called gemsol

    ramucirumab/ placebo was added to gemcitabine

  • RamucirumabDrug

    Also called CYRAMZA

    ramucirumab/ placebo was added to gemcitabine

Study groups in NCT03560973
Study groupRoleWhat they receive
Gemcitabine + RamucirumabExperimentalGemcitabine 1000 mg/m2 iv D1, D8 plus Ramucirumab 10 mg/kg iv (21 days cycles)
Receives: Drug: Gemcitabine; Drug: Ramucirumab
Gemcitabine + PlaceboPlacebo comparatorGemcitabine 1000 mg/m2 iv D1, D8 plus placebo (21 days cycles)
Receives: Drug: Gemcitabine

What is being measured

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

  1. OS

    time from the date of randomization to the date of death from any cause. gemcitabine with placebo,

    Measured: 36 months

Secondary outcomes (8)

  1. PFS

    Progression-free survival (PFS) is measured from the date of randomization to the date of radiographic documentation of progression (as defined by RECIST v1.1) or the date of death due to any cause, whichever is earlier. RECIST 1.1

    Measured: 36 months

  2. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).

    TEAEs, AESIs, SAEs, and hospitalizations, Clinical laboratory tests, vital signs, and physical examinations

    Measured: 36 months

  3. ORR

    ORR is the proportion of randomized patients achieving a best overall response of complete response (CR) or partial response (PR).

    Measured: 36 months

  4. DCR

    DCR is the proportion of randomized patients achieving a best overall response of CR, PR, or stable disease (SD).

    Measured: 36 months

  5. Predictive molecular markers

    polymorphisms associated with ramucirumab response

    Measured: 36 months

  6. Quality life

    survey completed by patients at cycles

    Measured: 36 months

  7. Predictive molecular markers

    Evaluation of circulating pro-angiogenic factors in response to Ramucirumab treatment

    Measured: 36 months

  8. Predictive molecular markers

    Effect of the mutational asset of the tumor on Ramucirumab response

    Measured: 36 months

Timeline

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

  1. First posted19 Jun 2018
  2. Study start22 Dec 2016
  3. Primary completion30 Jul 2018
  4. Study completion20 Jul 2022

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
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
164 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03560973
Sponsor's protocol ID
GOIRC-03-2016
Acronym
RAMES
Status last verified
Jul 2020
First submitted
18 May 2018
Last updated
13 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pinto C, Zucali PA, Pagano M, Grosso F, Pasello G, Garassino MC, Tiseo M, Soto Parra H, Grossi F, Cappuzzo F, de Marinis F, Pedrazzoli P, Bonomi M, Gianoncelli L, Perrino M, Santoro A, Zanelli F, Bonelli C, Maconi A, Frega S, Gervasi E, Boni L, Ceresoli GL. Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2021 Oct;22(10):1438-1447. doi: 10.1016/S1470-2045(21)00404-6. Epub 2021 Sep 6.

    PubMed 34499874

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gemcitabine and Ramucirumab in people with Mesothelioma, run by Gruppo Oncologico Italiano di Ricerca Clinica 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 16 inclusion and 32 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 13 Mar 2025. 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. Some participants in this study may receive a placebo. 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?

OS (time frame: 36 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 NCT03560973, 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 13 Mar 2025.

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