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Gastric CancerPhase 2a-MANTRANCT03627728

Study Maintenance Regorafenib vs Placebo, no Progression Patients After I Line Chemotherapy Metastatic Gastric Cancer

A Phase 2 study testing Regorafenib in people with Gastric Cancer, 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

Randomized, double-blind, placebo-controlled, multicenter Phase-II study. Approximately 120 subjects with CR/PR/SD after platinum compounds and fluoropyrimidines based regimens: up to 6 cycles of cisplatin and 5-fluorouracil or capecitabine, up to 12 cycles of FOLFOX, up to 8 cycles of XELOX, will be randomly assigned… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastric Cancer
What is being tested?
Regorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
67 participants
Where
1 siteItaly
Study dates
13 Jun 2018to 31 Oct 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male of female ≥ 18 years of age
  • Have an Eastern Cooperative Oncology Group performance status of 0 or 1 within 14 days prior to the initiation of study treatment
  • Diagnosis of histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction
  • HER2 negative gastric or gastroesophagel junction cancer ( ICH 0, IHC 1+, IHC + FISH -)
  • Locally advanced/metastatic gastric or gastroesophageal junction cancer
  • CR/PR/SD after first-line platinum compound and Fluoropyrimidines based chemotherapy
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  • Measurable disease according to RECIST 1.1 criteria
  • Have adequate bone marrow function, liver function, and renal function, as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment:
  • Total bilirubin 1.5 times the upper limit of normal (ULN)
  • Alanine aminotransferase and aspartate aminotransferase 3 times the ULN
  • Lipase 1.5 times the ULN
  • Serum creatinine 1.5 times the ULN
  • Glomerular filtration rate 30 mL/min/1,73 m2 according to the Modified Diet in Renal Disease abbreviated formula
  • International normalized ratio of prothrombin time and activated partial thromboplastin time 1.5 times the ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no underlying abnormality in coagulation parameters exists per medical history.
  • Platelet count 100,000 /mm3, hemoglobin 9 g/dL, absolute neutrophil count 1500/mm3 without transfusions or granulocyte colony stimulating factor and other hematopoietic growth factors
  • Alkaline phosphatase ≤ 2.5 times the ULN
  • Understand, be willing to give consent, and sign the written informed consent form (ICF) prior to undergoing any study-specific procedure.
  • If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment.
  • If female and of childbearing potential, or if male, agree to use adequate contraception (eg, abstinence, intrauterine device, oral contraceptive, or double-barrier method) based on the judgment of the investigator or a designated associate from the date on which the ICF is signed until 8 weeks after the last dose of study drug.

Who cannot join

  • Are taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort)
  • Have used biologic response modifiers, such as G-CSF, within 3 weeks of study entry
  • Have had prior treatment with regorafenib or any other VEGFR-targeting kinase inhibitor.
  • Completed their last dose of chemotherapy more than 8 weeks, whichever came later, prior to randomization.
  • Have had prior or concurrent cancer distinct in primary site or histology from GC or GJC within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, no-melanoma skin cancer, or superficial bladder tumors classified as noninvasive tumor (Ta), carcinoma in situ (Tis), or tumor invades lamina propria (T1).
  • Have had systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and/or hormonal therapy within 4 weeks prior to initiation of study treatment.
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  • Have unresolved toxicity higher than National Cancer Institute-Common Terminology for Adverse Events version 4.0 (NCI-CTCAE v 4.0) Grade 1 attributed to any prior therapy/procedure, excluding alopecia and/or oxaliplatin-induced neurotoxicity ≤ Grade 2 and hemoglobin ≥ 9 g/dL as per inclusion criteria
  • Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment.
  • Are pregnant.
  • Are breastfeeding.
  • Are unable to swallow oral tablets (crushing of study treatment tablets is not allowed).
  • Have congestive heart failure classified as New York Heart Association Class 2 or higher
  • Have had unstable angina (angina symptoms at rest) or new-onset angina 3 months prior to screening.
  • Have had a myocardial infarction 6 months prior to initiation of study treatment.
  • Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin.
  • Have uncontrolled hypertension (systolic blood pressure [SBP] 140 mmHg or diastolic blood pressure [DBP] 90 mmHg) despite optimal medical management.
  • Have had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months prior to the initiation of study treatment.
  • Have an ongoing infection with severity of Grade 2 or above (NCI-CTCAE v 4.0).
  • Have a known history of human immunodeficiency virus infection.
  • Have either active or chronic hepatitis B or C requiring treatment with antiviral therapy.
  • Have a seizure disorder requiring medication.
  • Have a history of organ allograft.
  • Have evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity.
  • Have had a hemorrhage or a bleeding event Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment.
  • Have a nonhealing wound, ulcer, or bone fracture.
  • Have renal failure requiring hemodialysis or peritoneal dialysis.
  • Have dehydration Grade 1 (NCI-CTCAE v 4.0).
  • Have interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained.
  • Have persistent proteinuria > 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (Grade 3, NCI-CTCAE v 4.0).
  • Have any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results.
  • Have a known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs.
  • Have any malabsorption condition.
  • Have a close affiliation with the investigational site (eg, be a close relative of the investigator) or be a dependent person (eg, be an employee or student working at the investigational site).
  • Untreated gastro-esophageus varices

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: Phase II Randomized Study of Maintenance Regorafenib vs Placebo in no Progression Patients After First-line Platinum and Fluoropyrimidines Based Chemotherapy in HER2 Negative Locally Advanced/Metastatic Gastric or Gastroesophagel Junction Cancer (a-MANTRA Study)

Randomized, double-blind, placebo-controlled, multicenter Phase-II study.

Approximately 120 subjects with CR/PR/SD after platinum compounds and fluoropyrimidines based regimens: up to 6 cycles of cisplatin and 5-fluorouracil or capecitabine, up to 12 cycles of FOLFOX, up to 8 cycles of XELOX, will be randomly assigned (1:1 ratio) to one of the following treatment groups:

Arm A: Placebo 4 tablets once daily on day 1-21, every 4 weeks, until intolerance or progression disease Arm B: Regorafenib 160 mg, 4 tablets once daily on days 1-21, every 4 weeks, until intolerance or progression disease Primary Variable: PFS1

Conditions
Gastric Cancer
Being tested
Regorafenib, placebo
Medical subject headings
Stomach Neoplasms

What participants receive

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

  • RegorafenibDrug

    Also called stivarga

    regorafenib/placebo

  • placeboOther

    regorafenib/placebo

Study groups in NCT03627728
Study groupRoleWhat they receive
regorafenibExperimentalRegorafenib 160 mg, 4 tablets once daily on days 1-21, every 4 weeks, until intolerance or progression disease
Receives: Drug: Regorafenib
placeboPlacebo comparatorPlacebo 4 tablets once daily on day 1-21, every 4 weeks, until intolerance or progression disease
Receives: Other: placebo

What is being measured

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

  1. PFS1

    Progression free survival will be calculated for all patients from the date of randomization until the date PD or death is first reported.

    Measured: 36 months

Secondary outcomes (6)

  1. OS

    time from date of randomization to the date of Death from any cause

    Measured: 36 months

  2. PFS2

    PFS 2 will be calculated from the start of second line therapy to PD or death

    Measured: 36 months

  3. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability

    The overall incidences of AEs will be summarized. Patients who experienced the same event on more than one occasion are counted only once in the calculation of the event frequency, at the highest intensity ever observed.

    Measured: 36 months

  4. Response Rate

    in patients who are randomized at enrollment to treatment with regorafenib vs placebo,

    Measured: 36 months

  5. quality of life To compare the patient treatment-related symptoms

    To compare the patient treatment-related symptoms as measured by the European Organization for research and treatment of cancer EORTC QLQ-C30, (days 1, week , 8, 16, 24, 32) , for patients in each treatment arm.

    Measured: up to 8 months

  6. biomarker evaluation

    To correlate the genetic mutational profile of the tumors with the RR and the OS of the patients

    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 posted13 Aug 2018
  2. Study start13 Jun 2018
  3. Primary completion21 Jun 2022
  4. Study completion31 Oct 2024

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
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03627728
Sponsor's protocol ID
GOIRC-05-2016
Acronym
a-MANTRA
Status last verified
Mar 2025
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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regorafenib in people with Gastric Cancer, 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 19 inclusion and 34 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?

PFS1 (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 NCT03627728.

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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