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

NCT03560973 | Completed Phase 2 DMC

• 1 other identifier: GOIRC-03-2016
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• OS

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

  36 months

Secondary Outcomes (8)

• PFS

  36 months

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

  36 months

• ORR

  36 months

• DCR

  36 months

• Predictive molecular markers

  36 months

Study Arms (2)

Gemcitabine + Ramucirumab

EXPERIMENTAL

Gemcitabine 1000 mg/m2 iv D1, D8 plus Ramucirumab 10 mg/kg iv (21 days cycles)

Drug: Gemcitabine; Drug: Ramucirumab

Gemcitabine + Placebo

PLACEBO COMPARATOR

Gemcitabine 1000 mg/m2 iv D1, D8 plus placebo (21 days cycles)

Drug: Gemcitabine

Interventions

Gemcitabine DRUG

ramucirumab/ placebo was added to gemcitabine

Also known as: gemsol

Gemcitabine + Placebo; Gemcitabine + Ramucirumab

Ramucirumab DRUG

ramucirumab/ placebo was added to gemcitabine

Also known as: CYRAMZA

Gemcitabine + Ramucirumab

Eligibility Criteria

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

You may qualify if:

• 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,
• a. 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead

Study Sites (1)

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

Reggio Emilia, 42123, Italy

Location

Related Publications (1)

• 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.

  PMID: 34499874 DERIVED

MeSH Terms

Conditions

Mesothelioma

Interventions

Gemcitabine; Ramucirumab

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Carmine Pinto, MD

  Gruppo Oncologico Italiano di Ricerca Clinica

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: June 19, 2018
• Study Start: December 22, 2016
• Primary Completion: July 30, 2018
• Study Completion: July 20, 2022
• Last Updated: March 13, 2025

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)