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Gastric AdenocarcinomaPhase 2NCT03783936

Trial of mFOLFOX6 + Trastuzumab + Avelumab in Gastric and Esophageal Adenocarcinomas

A Phase 2 study testing Oxaliplatin, Leucovorin and 5 fluorouracil in people with Gastric Adenocarcinoma and Esophageal Adenocarcinoma, run by Ashwin Somasundaram at 7 sites in United States.

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

The initial intent of the study was to be a multi-center single-arm open-label Simon's two-stage Phase II clinical trial of first-line mFOLFOX6 + trastuzumab + avelumab in metastatic HER2-amplified gastric and esophageal adenocarcinomas. Accrual will halt after completion of Stage I (enrollment of 18 patients). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Oxaliplatin, Leucovorin and 5 fluorouracil
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
7 sitesUnited States
Study dates
24 Jan 2019to 30 Aug 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Written informed consent and HIPAA authorization for release of personal health information prior to registration.
  • Age ≥ 18 years at the time of consent.
  • ECOG Performance Status of 0 or 1.
  • Histologically confirmed esophageal, gastroesophageal junction, or gastric adenocarcinoma, with unresectable or metastatic disease documented on diagnostic imaging studies.
  • HER2 amplification confirmed by standard of care testing of tumor specimen (3+ by immunohistochemistry, or 2+ on IHC with ISH with HER2/CEP17 ratio ≥2).
  • Radiographically measurable disease according to RECIST 1.1 within 28 days prior to registration.
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  • Adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration.
  • Absolute Neutrophil Count ≥ 1.5 x 10^9/L
  • Hemoglobin (Hgb) ≥ 9 g/dL (may have been transfused)
  • Platelets ≥ 100 x 10^9/L OR ≥ 75 x 10^9/L for patients who received Cycle 1 of mFOLFOX6 +/- trastuzumab prior to registration
  • Calculated creatinine clearance1 ≥ 30 mL/min OR creatinine ≤ 1.5 × upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN) (Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level >1.5 mg/dL, if their conjugated bilirubin is < 1.5× ULN)
  • Aspartate aminotransferase (AST) ≤ 2.5 × ULN OR ≤ 5x ULN in patients with known liver metastases
  • Alanine aminotransferase (ALT) ≤ 2.5 × ULN OR ≤ 5x ULN in patients with known liver metastases
  • Left ventricular ejection fraction (LVEF) ≥ 50% or above the lower limit of the institutional normal range, whichever is lower.
  • Females of childbearing potential must have a negative serum pregnancy test at screening. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
  • Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 210 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Who cannot join

  • Previous systemic therapy for stage IV disease - EXCEPT that patient may have received one cycle of mFOLFOX6 +/- trastuzumab within the 4 weeks prior to registration.
  • Active infection requiring intravenous systemic therapy.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Treatment with any investigational drug within 28 days prior to registration.
  • Prior immune checkpoint inhibitor therapy (i.e. anti-CTLA-4, anti-PD-L1, anti-PD-1), or HER2-directed therapy (including trastuzumab)
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis
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  • Untreated brain metastasis or brain metastasis treated within 4 weeks prior to enrollment.
  • Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
  • Serious cardiovascular event within 6 months prior to study entry, including myocardial infarction, malignant hypertension, severe/unstable angina, symptomatic congestive heart failure (≥ New York Heart Association Classification Class II), cerebral vascular accident, transient ischemic attack, or serious cardiac arrhythmia requiring medication.
  • History of organ allograft or allogeneic stem cell transplantation
  • Active autoimmune disease requiring systemic treatment in the past 3 months (for example with disease modifying agents, corticosteroids, or immunosuppressive drugs).
  • Exceptions Include:
  • Subjects with endocrine diseases stable on replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) or hormone suppression.
  • Subjects that require intermittent use of bronchodilators, local steroid injections, or inhaled or topical steroids
  • Subjects with vitiligo, psoriasis, Sjogren's syndrome, or resolved childhood asthma/atopy
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
  • Known history of Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Subjects with laboratory evidence of cleared HBV and HCV infection will be permitted.
  • Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5 Grade ≥ 3).
  • Persisting toxicity related to prior therapy (NCI CTCAE v5 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
  • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with informed consent, the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites
  • Winship Cancer Insititute of Emory University

    Atlanta, Georgia, 30322

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Northwestern University Feinberg School of Medicine

    Chicago, Illinois, 60611

  • City of Hope

    Duarte, California, 91010

  • University of Iowa Hospital and Clinics

    Iowa City, Iowa, 52242

  • Atlantic Health System

    Morristown, New Jersey, 07960

Other trials in United States

About this study

Official title: A Single Arm, Multi-center Phase 2 Trial of mFOLFOX6 + Trastuzumab + Avelumab in First-line, Metastatic, HER2-amplified Gastric and Esophageal Adenocarcinomas

The initial intent of the study was to be a multi-center single-arm open-label Simon's two-stage Phase II clinical trial of first-line mFOLFOX6 + trastuzumab + avelumab in metastatic HER2-amplified gastric and esophageal adenocarcinomas.

Accrual will halt after completion of Stage I (enrollment of 18 patients). This decision is not due to safety issues. Subjects currently on treatment will continue until criteria as defined in the protocol is met.

Medical subject headings
Adenocarcinoma Of Esophagus, Neoplasm Metastasis

What participants receive

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

Study groups in NCT03783936
Study groupRoleWhat they receive
Induction and MaintenanceOtherCycles 1-9; Induction; Cycle = 14 days mFOLFOX6 * oxaliplatin 85 mg/m2 IV Day 1 and * leucovorin 400 mg/m2 IV Day 1 and * 5 fluorouracil 400 mg/m2 IV bolus and 2400 mg/m2 IV over 46 hours Day 1 and Trastuzumab 6 mg/kg IV loading dose C1D1 then Trastuzumab 4 mg/kg IV Day 1 and Avelumab 800 mg IV Day 1 Cycles 10 and subsequent; Maintenance; Cycle = 14 days Trastuzumab 4 mg/kg Day 1 and Avelumab 800 mg Day 1
Receives: Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5 fluorouracil; Drug: Trastuzumab; Drug: Avelumab

What is being measured

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

  1. Best Objective Response Rate (bORR)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter(LD) of target lesions; Progressive Disease (PD): >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

    The bORR will be defined as the percentage of subjects whose best response by 24 weeks are either a CR or PR according to RECIST 1.1. For confirmed response, PR or CR need to be confirmed by repeat assessments that should be performed no less than 4 weeks. Otherwise, it will be considered as an unconfirmed response.

    Measured: 24 weeks

Secondary outcomes (5)
  1. Progression Free Survival (PFS)

    Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter(LD) of target lesions; Progressive Disease (PD): >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

    Progression Free Survival (PFS) will be defined as the time from the start date of treatment to the date of documented progression as determined by RECIST 1.1 or death from any cause.

    Measured: Time of treatment start until the criteria for disease progression or death, up to a maximum of 11 months.

  2. Progression Free Survival by iRECIST(iPFS)

    Immune-RECIST Criteria(iRECIST): Complete Response(iCR), Disappearance of all measurable and non-measurable lesions; Partial Response (iPR), >=30% decrease in tumor burden relative to baseline; Unconfirmed Progressive Disease (iUPD), >= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Confirmed Progressive Disease (iCPD), confirmation of iUPD (by further growth) at the next assessment; Stable Disease (iSD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

    iPFS will be defined as the time from the start date of treatment to the date of documented progression as determined by iRECIST criteria or death from any cause.

    Measured: Time of treatment start until the criteria for disease progression or death, up to a maximum of 11 months.

  3. Overall Survival (OS)

    Overall Survival (OS) will be defined as the time from start of treatment to the date of death from any cause, or date of last contact (censored).

    Measured: Time of treatment start until death or date of last contact, up to a maximum of 20 months

  4. Disease Control Rate (DCR)

    Disease Control Rate (DCR) will be defined as the total number of patients whose best responses are either a CR, PR, or SD divided by the number of response evaluable patients. Patients with best response of SD will need to maintain SD by 24 weeks to be considered to have received clinical benefit from the treatment regimen.

    Measured: Up to a maximum of 11 months.

  5. Number of Participants With Grade 3-4 Treatment Related Adverse Events

    The frequency and severity of all grade 3-4 treatment related adverse events are reported by CTCAE v5.

    Measured: AE had been recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) and/or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 20 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2018
  2. Study start24 Jan 2019
  3. Primary completion11 Sep 2020
  4. Study completion30 Aug 2022

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03783936
Sponsor's protocol ID
HCRN GI17-319
Status last verified
Nov 2023
First submitted
19 Dec 2018
Last updated
19 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lee MS, Chao J, Mulcahy MF, Kasi PM, Alistar AT, Mukherjee S, Akce M, Moore DT, McRee AJ, Somasundaram A. Phase II study of avelumab and trastuzumab with FOLFOX chemotherapy in previously untreated HER2-amplified metastatic gastroesophageal adenocarcinoma. Oncologist. 2025 Jul 4;30(7):oyaf195. doi: 10.1093/oncolo/oyaf195.

    PubMed 40571483

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Oxaliplatin, Leucovorin and 5 fluorouracil in people with Gastric Adenocarcinoma and Esophageal Adenocarcinoma, run by Ashwin Somasundaram at 7 sites in United States.

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 18 inclusion and 22 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 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. 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. 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?

Yes. Results are posted in the registry (first posted 19 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Best Objective Response Rate (bORR) (time frame: 24 weeks). 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 NCT03783936, which also lists 1 linked publication.

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 19 Dec 2023.

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