A Phase 2, Fast Real-time Assessment of Combination Therapies in Immuno-Oncology Study in Participants with Advanced Gastric Cancer (FRACTION-Gastric Cancer)
- Conditions
- Gastric Cancer10017990
- Registration Number
- NL-OMON55766
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 17
1) Participants must provide consent for 3 mandatory tumor biopsy samples (as
detailed in*J* below).
2) All participants must have inoperable, advanced, or metastatic GC or GEJ
carcinoma(including adenocarcinoma arising from the lower esophagus) and have
histologically confirmed predominant adenocarcinoma. The documentation of GEJ
involvement can include biopsy, endoscopy, or imaging.
3) Participants with human epidermal growth factor receptor 2 (HER2)
overexpressing tumor who progress after trastuzumab (or are ineligible for or
unwilling to be treated with trastuzumab) are eligible to be enrolled.
4) Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, and/or
chemoradiotherapy are permitted as long as the last administration of the last
regimen (whichever was given last) occurred at least 4 weeks prior to
randomization.
5) Participants must have an Eastern Cooperative Oncology Group performance
status of <= 1 (see Appendix 7)., 6) Track-specific eligibility criteria
Track 1: anti-PD-1, anti-PD-L1, and anti-CTLA-4 treatment-naïve participants
1).Participants must not have received any anti-PD-1, anti-PD-L1, or
anti-CTLA-4 treatment prior to this study. Participants previously treated with
agents other than anti-PD-1, anti-PD-L1, or anti-CTLA-4 are eligible for Track
1.
2).Participants may have been offered platinum-based chemotherapy for
progressive or recurrent disease.
3).Participants must have documented PD-L1 tumor status following a required
pretreatment biopsy as described below.
After signing informed consent, participants will be required to submit a fresh
tumor biopsy meeting the criteria defined above for IHC staining to determine
PD-L1 status., Track 2: anti-PD-1, anti-PD-L1, or anti-CTLA-4
treatment-experienced participants
1).Participants must have had progressive or recurrent disease during or after
anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment. (Participants treated with any
study treatment targeting PD-1, PD-L1, or CTLA-4 will be considered anti-PD-1,
anti-PD-L1, or anti-CTLA-4 treatment experienced, respectively)
2).Participants may have been offered a platinum-based chemotherapy for GC or
GEJ.
The platinum-based chemotherapy may have been in the adjuvant,
neoadjuvant, or recurrent setting.
3).Participants who have had prior treatment with any 1 of the agents (or any
other agent targeting PD-1, PD-L1, or CTLA-4) in monotherapy or in any
combination regimen in a FRACTION-Gastric Cancer Sub-Protocol are eligible for
treatment on Track 2.
4).Participants who have had prior combination treatment with the same IO
combination agents (or IO agents directed against the same targets) as 1 of the
combination regimens in a FRACTION-Gastric Cancer Sub-Protocol are eligible for
study treatment on Track 2 but must be randomized to another combination
regimen.
5).After signing informed consent, participants will be required to submit a
fresh tumor biopsy for IHC staining to determine PD-L1 status., 7) At the time
of screening, participants must have a life expectancy of at least 3 months
following their most recent chemotherapy or immunotherapy for entry into all
Tracks.
a. Participants who wish to be re-randomized to a new study treatment
combination on Track 2 following progression on a prior study treatment in
Tracks 1 or 2 must have a li
a) Participants with overexpressing HER2 positive tumor and previously
untreated with trastuzumab are excluded; participants who are ineligible for or
unwilling to be treated with trastuzumab are still eligible.
b) Participants with ascites that cannot be controlled with appropriate
interventions.
c) Participants must not have suspected, known, or progressive CNS metastases;
have untreated CNS metastases; or have the CNS as the only site of disease.
i) Participants are eligible if CNS metastases are adequately treated and
participants neurologically return to baseline (except for residual signs or
symptoms related to the CNS treatment) for at least 2 weeks prior to study
entry. In addition, participants mus tbe either off corticosteroids or on a
stable or decreasing dose of prednisone <= 10 mg daily (or equivalent) for at
least 2 weeks prior to study entry.
ii) Participants must not have leptomeningeal disease or carcinomatous
meningitis.
d) Participants must not have prior malignancy active within the previous 3
years except for locally curable cancers that have been apparently cured, such
as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma
in situ of the prostate, cervix, or breast.
e) Participants must not have other active malignancy requiring concurrent
intervention.
f) Participants must not have received a prior organ allograft.
g) Participants must not have received any anti-cancer treatment (eg,
chemotherapy,
radiotherapy [except for palliative radiotherapy, which can be received at
least 2 weeks prior to study treatment]; biologics; or immunotherapies,
including investigational treatments) within 4 weeks prior to the first dose of
study treatment administration.
i) Participants who have received noncytotoxic anti-cancer therapies (eg, prior
use of targeted treatment) and who completed treatment at least 4 weeks or 5
half-lives (whichever is shorter) prior to the first dose of study treatment
are eligible to enroll.
h) Participants must not have active, known, or suspected autoimmune disease.
i) Participants with type I diabetes mellitus, hypothyroidism only requiring
hormone
replacement treatment, skin disorders (such as vitiligo, psoriasis, or
alopecia) not
requiring systemic treatment, or conditions not expected to recur in the
absence of an external trigger are permitted to enroll.
Participants must not have a condition requiring systemic treatment with either
corticosteroids (prednisone > 10 mg daily or equivalent) or other
immunosuppressive medications within 14 days of study treatment administration.
i) Inhaled or topical steroids and adrenal replacement steroid (prednisone > 10
mg daily or equivalent) are permitted in the absence of active autoimmune
disease.
j) Participants must not have a history of life-threatening toxicity related to
prior IO
treatment (eg, anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or
treatment specifically targeting T-cell co-stimulation or immune checkpoint
pathways).
k) Participants must not have interstitial lung disease that is symptomatic or
may interfere with the detection or management of suspected treatment-related
pulmonary toxicity.
l) Participants must not have uncontrolled or significant cardiovascular
disease including, but not limited to, any o
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To investigate the efficacy (by measuring Overall Response Rate, duration of<br /><br>response, and progression free survival rate at 24 weeks) of each treatment<br /><br>combination within the FRACTION study(as compared to Nivolumab in combination<br /><br>with Ipilimumab when applicable) in patients with advanced Gastric Cancer</p><br>
- Secondary Outcome Measures
Name Time Method <p>To investigate the additional safety and tolerability of each study treatment<br /><br>combination in patients with advanced Gastric Cancer.<br /><br><br /><br>Exploratory objectives:<br /><br>-To determine the pharmacodynamics effects of the medications by evaluating a<br /><br>selection of biomarkers in blood and tumour biopsy samples.<br /><br>-To assess the overall survival in treated patients<br /><br>-To explore the potential associations between anti-tumour activity or safety<br /><br>and select biomarker measures in tumor biopsy specimens and blood prior to<br /><br>study treatment and following drug administration.<br /><br>-To evaluation the pharmacokinetics of each investigational product.<br /><br>-To evaluate the immunogenicity of each investigational product.<br /><br>-To evaluate disease-related symptoms improvement using the GaCs in treated<br /><br>patients.<br /><br>-To evaluate general health using the EQ-5D in treated patients. </p><br>