`A Phase III open-label, multicenter trial of maintenance therapy with avelumab (MSB0010718C) versus continuation of first-line chemotherapy in subjects with unresectable, locally advanced or metastatic, adenocarcinoma of the stomach, or of the gastro-esophageal junction
- Parkland Health & Hospital System
Udit Verma, M.D.
The open-label study design is justified based on the following:
Double-blind controlled study would be impossible due to differences in treatment schedule and toxicity profile that would unmask treatment assignment
overall survival was chosen as one of the primary endpoints because this is an unequivocal
measurement of clinical benefit that will not be confounded by the open-label nature of the study.
The PFS time was chosen as one of the primary endpoints for the following reasons:
-as acknowledged by the Committee for Medicinal Products for Human use (CHMP)
Scientific advisory group for oncology (answers from the CHMP Scientific advisory
Group for oncology for Revision of the anticancer guideline [eMa/768937/2012]), PFS
time is regarded as an acceptable endpoint in the metastatic setting if the improvement in
median PFS is in the order of 3 to 4 months or longer in the case the prognosis for oS is in
the order of 2 to 3 years or less.
-PFS can reflect tumor growth and be evaluated before the determination of a survival
benefit. its determination is not confounded by subsequent therapy. PFS time will be
supported by the primary endpoint of oS time and the key secondary endpoint oRR as
well as patient-reported outcomes data in the Switch-maintenance Phase.
-as the anti-PD-L1 (avelumab) mechanism of action is different from that of the drugs that
are usually used in the treatment of second-line gastric patients, it is very unlikely that the
administration of avelumab will have a negative impact on the subsequent therapies, which makes PFS time an adequate clinical endpoint in support of approval in oncology (with respect to answers from the CHMP Scientific advisory Group for oncology for Revision
of the anticancer guideline).
For inclusion in the trial, all of the following inclusion criteria must be fulfilled:
1. Has read, understood and signed written informed consent before any trial-related procedure
is undertaken that is not part of the standard patient management
2. Male or female subjects aged >= 18 years
3. Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or a
minimum number of 7 (preferably 10) unstained tumor slides suitable for PD-L1 expression
4. Disease must be measurable by RECIST v1.1
5. Subjects with histologically confirmed unresectable locally advanced or metastatic
adenocarcinoma of the stomach or GEJ (Gastro-esophageal junction)
6. ECOG PS of 0 to 1 at trial entry
7. Estimated life expectancy of more than 12 weeks
8. Adequate hematological function defined by white blood cell (WBC) count >= 2.5 x 109/L with
absolute neutrophil count (ANC) >= 1.5 x 109/L, lymphocyte count >= 0.5 x 109/L, platelet count
>= 100 x 109/L, and hemoglobin >= 9 g/dL (may have been transfused)
9. Adequate hepatic function defined by a total bilirubin level <= 1.5 x the upper limit of normal
(ULN) range and AST and alanine aminotransferase (ALT) levels <= 2.5 x ULN for all subjects
10. Adequate renal function defined by an estimated creatinine clearance >= 30 mL/min according
to the Cockcroft-Gault formula (or local institutional standard method)
11. Negative blood pregnancy test at Screening for women of childbearing potential. For the
purposes of this trial, women of childbearing potential are defined as:
* All female subjects after puberty unless they are post-menopausal for at least 2 years, are surgically sterile or are sexually inactive.
12. Highly effective contraception (i.e. methods with a failure rate of less than 1 % per year) for
both male and female subjects if the risk of conception exists (Note: The effects of the trial
treatment on the developing human fetus are unknown; thus, women of childbearing potential
and men must agree to use highly effective contraception, defined in Appendix II Guidance
on Contraception or as stipulated in national or local guidelines. Highly effective
contraception must be used 28 days prior to first trial treatment administration, for the duration
of trial treatment, and at least for 60 days after stopping trial treatment. Should a woman
become pregnant or suspect she is pregnant while she or her partner is participating in this
trial, the treating physician should be informed immediately.)
Inclusion Criteria for Pregnant Partners if one is identified:
- The individual must have become pregnant during the protocol-specified time period.
- The individual's partner must be a participant in the study.