Study of maintenance Regorafenib vs Placebo in no progression patients after first-line chemotherapy in locally advanced/metastatic gastric or gastroesophagel junction cancer patients (a-MANTRA Study)
- Conditions
- o progression patients after first-line platinum and fluoropyrimidines based chemotherapy in HER2 negative locally advanced/metastatic gastric or gastroesophagel junction cancerMedDRA version: 21.1Level: LLTClassification code 10071114Term: Metastatic gastric adenocarcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003031-38-IT
- Lead Sponsor
- GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 120
1. Male of female = 18 years of age
2. Have an Eastern Cooperative Oncology Group performance
status of 0 or 1 within 14 days prior to the initiation of study
treatment
3. Diagnosis of histologically confirmed adenocarcinoma of the
stomach or gastroesophageal junction
4. HER2 negative gastric or gastroesophagel junction cancer (
ICH 0, IHC 1+, IHC + FISH -)
5. Locally advanced/metastatic gastric or gastroesophageal
junction cancer
6. CR/PR/SD after first-line platinum compound and
Fluoropyrimidines based chemotherapy
7. Measurable disease according to RECIST 1.1 criteria
8. Have adequate bone marrow function, liver function, and
renal function
9. Understand, be willing to give consent, and sign the written
informed consent form (ICF) prior to undergoing any studyspecific
procedure.
10. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
1. 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)
2. Have used biologic response modifiers, such as G-CSF,
within 3 weeks of study entry
3. Have had prior treatment with regorafenib or any other
VEGFR-targeting kinase inhibitor.
4. Completed their last dose of chemotherapy more than
8 weeks, whichever came later, prior to randomization.
5. 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).
6. 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.
7. 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 oxaliplatininduced
neurotoxicity = Grade 2 and hemoglobin = 9 g/dL as
per inclusion criteria (see Section 0).
8. Have had a major surgical procedure, open biopsy, or
significant traumatic injury within 28 days prior to initiation
of study treatment.
9. Are pregnant.
10. Are breastfeeding.
11. Are unable to swallow oral tablets (crushing of study
treatment tablets is not allowed).
12. Have congestive heart failure classified as New York Heart
Association Class 2 or higher
13. Have had unstable angina (angina symptoms at rest) or newonset
angina ¿¿3 months prior to screening.
14. Have had a myocardial infarction ¿¿6 months prior to
initiation of study treatment.
15. Have cardiac arrhythmias requiring anti-arrhythmic therapy,
with the exception of beta blockers or digoxin.
16. Have uncontrolled hypertension (systolic blood pressure
[SBP] ¿¿140 mmHg or diastolic blood pressure [DBP] ¿¿90
mmHg) despite optimal medical management.
17. 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.
18. Have an ongoing infection with severity of Grade 2 or above
(NCI-CTCAE v 4.0).
19. Have a known history of human immunodeficiency virus
infection.
20. Have either active or chronic hepatitis B or C requiring
treatment with antiviral therapy.
21. Have a seizure disorder requiring medication.
22. Have a history of organ allograft.
23. Have evidence or history of any bleeding diathesis (including
mild hemophilia), irrespective of severity.
24. Have had a hemorrhage or a bleeding event ¿¿Grade 3 (NCICTCAE
v 4.0) within 4 weeks prior to the initiation of study
treatment.
25. Have a nonhealing wound, ulcer, or bone fracture.
26. Have renal failure requiring hemodialysis or peritoneal
dialysis.
27. Have dehydration ¿¿Grade 1 (NCI-CTCAE v 4.0).
28. Have interstitial lung disease with ongoing signs and
symptoms at the time informed consent is obtained.
29. Have persistent proteinuria > 3.5 g/24 hours measured by
urine protein-creatinine ratio from a random urine sample
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Progression Free Survival 1 (PFS 1);Secondary Objective: -Overall Survival<br>-Progression Free Survival 2 (PFS2)<br>-Safety<br>-Objective Response Rate<br>-Quality of Live;Primary end point(s): Progression Free Survival (PFS) in all randomized patient;Timepoint(s) of evaluation of this end point: Progression Free Survival (PFS)<br>Imaging studies will be performed at baseline, 8, 16, 24 and<br>32 weeks, and then every 12 weeks. The objective<br>(confirmed) response and the progression-free survival will<br>be assessed by RECIST criteria. Progression free survival<br>will be calculated for all patients from the date of<br>randomization until the date PD or death is first reported.<br>
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Overall Survival Safety, Objective Response Rate, Quality of Live in all randomized patient; Progression Free Survival 2 (PFS2);Timepoint(s) of evaluation of this end point: From the start to the end date of patient's participation in the study ; PFS 2 will be calculated from the start of second line therapy to Progression or death