Primary ObjectivesThe main purpose of this study is to compare how long subjects with oesophageal cancer live overall (called overall survival, OS) or live without disease progression (called progression free survival, PFS) after receiving BMS-…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* The co-primary outcome measure for this study overall survival and
progression free survival (PFS) as assessed by a Blinded Independent Central
Review (BICR).
o Overall survival is defined as the time between the date of randomization and
the date of death. For those without documentation of death, OS will be
censored on the last date the participant was known to be alive.
o Progression free survival is defined as the time between the date of
randomization and the date of the first documented PD per BICR or death due to
any cause.
Secondary outcome
The secondary outcome measures for this study are as follows:
- Objective Response Rate, as assessed by a BICR, per RECIST 1.1
- Duration of Response
Background summary
Stomach cancer (or gastric cancer; referred to as GC from here on out) is the
5th leading cancer and the third leading cause of cancer-related death
worldwide. The incidence of GC varies across different geographies, with over
70% occurring in developing countries. Upon diagnosis, patients often already
have advanced disease (about 40% of newly diagnosed cases in the United States
and Europe).
Gastric cancer, including gastro-oesophageal junction cancer (GEJ ), is a quite
diverse disease with several established risk factors, including environmental,
genetic, and behavioural risks. Although there has been a steady decline in
deaths due to GC (down to dietary and lifestyle changes and to decreasing
infection with Helicobacter pylori) the incidence of GEJ tumors has increased
considerably due to increases in risk factors such as obesity and
gastroesophageal reflux disease.
Stomach cancer and GEJ is treated in much the same way with platinum compounds
and fluoropyrimidines. While these cytotoxic agents are clinically active,
with a 30% to 50% objective response rate (ORR) in the first line setting, this
clinical activity is accompanied by high toxicity. In addition, despite ORRs of
30% to 50%, chemotherapy has resulted in few participants achieving complete
response (CR); therefore, new treatment options are needed to improve survival
and response as well as decrease toxicity in 1L GC/GEJ cancer.
In the past decade, multiple new investigational drugs with mainly molecular
targets have been investigated in the 1L setting as add-ons to backbone
platinum and fluoropyrimidine treatment.
These agents, with the exception of trastuzumab, which targets the human
epidermal growth factor receptor 2 (HER2)-positive population,have failed to
show a survival benefit in randomized trials. The reasons include regional
differences in effectiveness, with the highest survival rate but smallest
benefit noted in Asia and the shortest median Overall Survival but greatest
benefit in Western countries. Thus, a regional approach might be appropriate in
1L GC/GEJ treatment development, and this study will mainly focus on Western
countries where great unmet medical needs remain.
This is a randomized, active-controlled, blinded, phase 3 trial of BMS-986213
(fixed dose combination of relatlimab plus nivolumab) in combination with
chemotherapy versus placebo plus chemotherapy as first-line treatment in
patients in inoperable, locally advanced or metastatic LAG-3 positive gastric
or gastroesophageal junction cancer. About 678 subjects in total are expected
to participate in the study, with approximately 8 patients in the Netherlands.
Study objective
Primary Objectives
The main purpose of this study is to compare how long subjects with oesophageal
cancer live overall (called overall survival, OS) or live without disease
progression (called progression free survival, PFS) after receiving BMS-986213
with chemotherapy versus chemotherapy alone.
Overall survival means the length of time a patient lives with their cancer
from the point of diagnosis or start of treatment. It is a good indicator of
how well the treatment is working and it used as a standard measure in clinical
trials.
The secondary objectives of patients with inoperable, untreated, locally
advanced or metastatic LAG-3 positive stomach cancer or gastroesophageal
junction cancer (cancer of the food pipe) are:
1) To assess the overall safety and tolerability of BMS-986213 in combination
with chemotherapy with chemotherapy alone
2) To compare objective response rate (ORR) of BMS-986213 in combination with
chemotherapy and with ORR of chemotherapy alone, as assessed by a blinded
independent committee and by investigator. ORR means the proportion of patients
with a certain tumour size reduction and for a certain period of time.
3) To estimate Duration of Response (DOR) of BMS-986213 in combination with
chemotherapy and with DOR of chemotherapy alone, as assessed by the independent
blinded committee and by investigator. The time to relapse or progression is
the duration of response.
PFS means the length of time a patient lives with their cancer from the point
of diagnosis or start of treatment without it getting worse. It is a good
indicator of how well the treatment is working and it used as a standard
measure in clinical trials.
Study design
This is a Phase 3, randomised, blinded, three-arm study of BMS-986213
(fixed-dose combination [FDC] relatlimab/nivolumab) or nivolumab in combination
with investigator*s choice chemotherapy versus placebo in combination with
investigator*s choice chemotherapy as first-line treatment in participants with
unresectable, untreated, locally advanced or metastatic LAG-3 positive gastric
or GEJ adenocarcinoma.
A safety evaluation will be conducted for the first 30 participants enrolled
and randomised in the study. These 30 participants will receive a minimum of 1
cycle treatment (a 6-week cycle) and have a minimum of 4-month follow-up.
Depending on the treatment arm, the participant will receive BMS-986213 in
combination with investigator*s choice chemotherapy, nivolumab in combination
with investigator*s choice chemotherapy or placebo in combination with
investigator*s choice chemotherapy in a blinded manner. One cycle of treatment
is defined as 6 weeks.
Patients will undergo a number of screening procedures to assess if they are
eligible to take part in the study. A pre-treatment tumor sample to determine
LAG3 and PD-L1 status is required to be submitted from all participants prior
to randomization.
Throughout the study, patients will have the following procedures: up to 3
biopsies, CT/MRI scans, physical exams, ECGs, vital signs, urine and blood
sampling and pregnancy testing. They will also have to complete health related
questionnaires regularly. Depending on chemotherapy regimen they are given,
patients will typically come to the hospital for treatment every 3 weeks for
infusions with some oral chemotherapy in between (XELOX and SOX regimen). The
FOLFOX chemotherapy regimen is more intense with more regular and longer
infusions (one of which, fluorouracil is over 24 hours).
On-study tumor assessments will begin 6 weeks from randomization and will
continue every 6 weeks up to week 48 and every 12 weeks thereafter.
All patients will receive their treatment until their cancer progresses (as
evaluated by CT scan or MRI), unacceptable toxicity, or if they withdraw their
consent to continue the treatment, whichever comes first.
Patients will be expected to receive their treatment for up to 30 weeks (about
5 cycles) and be in follow-up for up to 5 years.
Follow-up
After stopping their treatments, patients will be asked to come back to the
hospital for 2 follow-up visits, at 30 and 100 days after their last dose of
study treatment, respectively.
Additional visits after follow-up visits (survival visits)
After the 2 in-person follow up visits, patients may come to the clinic or they
may be contacted by phone, every 3 months, to be asked about their possible
subsequent cancer therapies. They will be asked to complete questionnaires
about their wellbeing and how cancer is affecting their life.
Intervention
The medical interventions include treatment with BMS-986213, nivolumab and
standard of care chemotherapy. All treatments will be supplied by the sponsor.
Patients will be randomised 2:1:2 to
one of 3 treatment arms:
1) BMS-986213 in combination with investigator*s choice chemotherapy
2) Nivolumab in combination with investigator*s choice chemotherapy
3) Placebo in combination with investigator*s choice chemotherapy
The chemotherapy treatment regimens are as follows:
* FOLFOX (oxaliplatin, leucovorin and fluorouracil)
* XELOX (oxaliplatin and capecitabine)
* SOX (oxaliplatin and S1)
The study doctor will decide on the chemotherapy regimen for the patient.
Patients will receive treatment until disease progression, unacceptable
toxicity or withdrawal of consent.
Study burden and risks
As part of the trial, patients will be expected to attend multiple clinic
visits where they will undergo physical examinations, vital sign measurements,
blood tests for safety assessment, pregnancy testing (for females of
child-bearing potential) and monitoring for adverse events. Patients will be
asked to complete questionnaires about their quality of life. Blood will also
be collected at certain visits for research purposes (PK and biomarker
studies). If there is no archive tumour tissue available or the sample was
taken too long ago (more than 3 months), patients will be required to have a
biopsy in order to participate. Patients will undergo radiographic assessment
of their tumours by CT or MRI at screening and then every 6 weeks for the first
year and every 12 weeks thereafter until disease progression or treatment
discontinuation. The frequency of visits and number of procedures carried out
during this trial would typically be considered over and above standard of
care. The procedures are carried out by trained medical professionals and every
effort will be made to minimise any risks or discomfort to the patient.
Treatment for cancer often has side effects, including some that are life
threatening. To assure an ongoing favourable risk/benefit assessment for
participants enrolled onto the study, an independent Data Monitoring Committee
(DMC) will be established to provide oversight of safety and efficacy
considerations. Additionally, the DMC will provide advice to the sponsor
regarding actions the committee deems necessary for the continuing protection
of participants enrolled in the study.
BMS will conduct a rigorous safety monitoring to ensure participants* safety by
regularly and systematically reviewing safety data; the reported safety events
will be closely followed-up; sites and study investigators will receive an
training on the implementation of the BMS-986213 and nivolumab toxicity
management strategies.
New immune system targeted therapy (immunotherapies) such as nivolumab and
BMS-986213 could potentially provide clinical benefit and improvements in the
outcomes for patients with this disease (improvement in progression free and
overall survival). However, with all experimental drugs and clinical trials,
there are known and unknown risks. Study medication and procedure related risks
are outlined in the patient information sheet in detail to ensure the patients
are fully informed before agreeing to take part in the study.
Uxbridge Business Park - Sanderson Road - Unit 2 GB
Uxbridge UB8 1DH
GB
Uxbridge Business Park - Sanderson Road - Unit 2 GB
Uxbridge UB8 1DH
GB
Listed location countries
Age
Inclusion criteria
1) Males and Females, * 18 years of age
2) All subjects must have a confirmed diagnosis (using tumour tissue) of unresectable, locally advanced or metastatic gastric or GEJ adenocarcinoma. The documentation of GEJ involvement can include biopsy, endoscopy, or imaging.
3) Subject must be previously untreated with systemic treatment including HER 2 inhibitors given as primary therapy for unresectable, locally advanced or metastatic gastric or GEJ adenocarcinoma
4) Allowed Prior Therapies: Prior adjuvant or neoadjuvant chemotherapy, radiotherapy and/or chemoradiotherapy for GC or GEJ cancer are permitted as long as the last administration of the last regimen (whichever was given last) occurred at least 6 months prior to randomization. Palliative radiotherapy is allowed and must be completed 2 weeks prior to randomization. Chinese traditional medicines with an approved indication of cancer treatment are permitted as long as the last administration occurred at least 2 weeks prior to randomization.
5) Subject must have at least one measurable lesion or evaluable disease by CT or MRI per RECIST 1.1 criteria; radiographic tumor assessment should be performed within 28 days prior to randomization.
6) HER2/neu protein negative LAG3 positive
7) Adequate organ function
8) ECOG performance status score of 0 or 1
9) Tumor tissue must be provided for LAG-3, PD-L1, MSI, TMB biomarker analyses prior to randomization.
Exclusion criteria
1) LAG3 negative
2) HER2 positive
Medical Conditions
3) Subjects with untreated known brains metastases.
4) 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.
5) Subjects with active, known, or suspected autoimmune disease.
6) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
7) All toxicities attributed to prior anti-cancer therapy other than hearing loss, alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4) or baseline before administration of study drug.
8) Subjects with > Grade 1 peripheral neuropathy.
9) Subjects with ascites which cannot be controlled with appropriate interventions
10) Uncontrolled or significant cardiovascular disease
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-004896-30-NL |
| CCMO | NL65238.056.18 |
| Other | U1111-1206-3033 |