AdenocarcinomaPhase 2NCT03000179
Safety and Efficacy of Avelumab in Small Intestinal Adenocarcinoma
A Phase 2 study testing Avelumab in people with Adenocarcinoma, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
Trial summary
This is a single-agent, open label, one-arm phase 2 pilot study of avelumab in patients with advanced or metastatic adenocarcinoma of the small intestine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma
- What is being tested?
- Avelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Mar 2017to 3 Aug 2021
- 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
- Signed and dated written informed consent.
- Male or female ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Histologically confirmed adenocarcinoma of the small intestine that is advanced (not amenable to surgery) or metastatic (clinical stage IV). For the purposes of this study, ampullary tumors are considered a part of the duodenum and are classified as adenocarcinomas of the small intestine.
- At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria that has not been previously irradiated and which can be followed by CT or MRI.
- Adequate organ function including:
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- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
- Platelets ≥ 100 × 109/L
- Hemoglobin ≥ 9/g/dL (may have been transfused)
- Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present)
- Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 30 mL/min as calculated using the Cockcroft-Gault (CG) equation
- Archival tissue [paraffin block(s) or unstained slides from paraffin block(s)] from the primary tumor and/or a metastatic site judged reasonably available prior to initiating treatment, or willingness to undergo fresh pre-treatment tumor biopsy. (Prior to initiating treatment, the screening team must have documentation that an archival or fresh tumor specimen has been requested from a local or outside facility. However, physical possession of requested tissue or waiting for histological analysis or confirmation that an acquired specimen contains tumor tissue sufficient for analysis is not a requirement prior to initiating treatment.) If no archival tissue is available and patient consents to a fresh biopsy, but the patient's lesion is deemed inaccessible to safe biopsy, the patient will be allowed to enroll if otherwise eligible.
- Female patients of childbearing potential and male patients able to father children who have female partners of childbearing potential must agree to use one highly effective method (defined as less than 1% failure rate per year) and one additional effective method of contraception (Appendix 4) from 15 days prior to first trial treatment administration until at least 60 days after study participant's final dose of avelumab.
- Females of childbearing potential are defined as those who are not surgically sterile or post-menopausal (i.e. patient has not had a bilateral tubal ligation, a bilateral oophorectomy, or a complete hysterectomy; or has not been amenorrheic for 12 months without an alternative medical cause). Post-menopausal status in females under 55 years of age should be confirmed with a serum follicle-stimulating hormone (FSH) level within laboratory reference range for postmenopausal women.
- Male patients able to father children are defined as those who are not surgically sterile (i.e. patient has not had a vasectomy).
- Serum pregnancy test (for females of childbearing potential) negative at screening.
- Re-enrollment of a subject that has discontinued the study as a pre-treatment screen failure (i.e. a consented patient who did not receive avelumab) is permitted. If re-enrolled, the subject must be re-consented. Only the screening procedures performed outside of protocol-specified timing must be repeated.
Who cannot join
- There is no restriction on the number of prior therapies. However, prior therapy with antibody or drug specifically targeting T cell regulatory proteins, including but not limited to the following is not allowed: Prior immunotherapy with IL-2 or IFN-α, or an anti-PD-1 (including nivolumab), anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyteassociated antigen-4 (CTLA-4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Within 28 days before first dose of avelumab: Anti-cancer treatment, major surgery requiring general anesthesia, or the use of any investigational agent.
- Within 14 days before first dose of avelumab: Therapeutic or palliative radiation therapy. (Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab.)
- Current use of immunosuppressive medication, except the following:
- Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intra-articular, intranasal, and inhaled);
- Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent are permitted;
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- A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. CT scan premedication against contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by a contact allergen) is permitted.
- Previous malignant disease other than adenocarcinoma of the small intestine within the last 5 years, with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of avelumab AND additional therapy not required while receiving study treatment).
- All subjects with brain metastases, expect those meeting the following criteria:
- Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment
- No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable.
- Subjects must be either off steroids or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent)
- Receipt of any organ transplantation including allogeneic stem-cell transplantation.
- Significant acute or chronic infections requiring systemic therapy.
- Known history of testing positive for human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS).
- Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
- Active autoimmune disease with reasonable possibility of clinically significant deterioration when receiving an immunostimulatory agent:
- Subjects with Type 1 diabetes mellitus, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
- Interstitial lung disease that is symptomatic or which may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- Uncontrolled asthma [defined as having 3 or more of the following features of partially controlled asthma within 28 days prior to starting study treatment: Daytime symptoms more than twice per week, any limitation of activities, any nocturnal symptoms/awaking, need for reliever/rescue inhaler more than twice per week, or known lung function (PEF or FEV1) without administration of a bronchodilator that is < 80% predicted or personal best (if known)].
- Current symptomatic congestive heart failure (New York Heart Association > class II), unstable cardiac arrhythmia requiring therapy (e.g. medication or pacemaker), unstable angina (e.g. new, worsening or persistent chest discomfort), or uncontrolled hypertension (systolic > 160 mmHg or diastolic > 100mmHg). Or any of the following occurring within 6 months (180 days) prior to first dose of avelumab: Myocardial infarction, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, or serious cardiac arrhythmia requiring medication. (Use of antihypertensive medication to control blood pressure is allowed.)
- Concurrent treatment with a non-permitted drug.
- Requirement of anticoagulant therapy with oral vitamin K antagonists such as Coumadin (warfarin). Low-dose anticoagulants for the maintenance of patency in a central venous access device or the prevention of deep vein thrombosis or pulmonary embolism is allowed. Therapeutic use of low molecular weight heparin is allowed.
- Persisting toxicity related to prior therapy that has not reduced to Grade 1 [National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.03; however, alopecia and sensory neuropathy Grade ≤ 2 is acceptable.
- Known severe (Grade ≥ 3 NCI-CTCAE v4.03) hypersensitivity reactions to monoclonal antibodies, including hypersensitivity to the investigational agent or any component in its formulations, or history of anaphylaxis.
- Vaccination within 28 days of the first dose of avelumab and while on trial is prohibited, except for administration of inactivated vaccines (for example, inactivated influenza vaccine).
- Pregnant or breastfeeding females.
- Known alcohol or drug abuse.
- Prisoners or subjects who are involuntarily incarcerated.
- Other severe acute or chronic medical condition, including colitis, inflammatory bowl disease, pneumonitis, pulmonary fibrosis, or psychiatric condition 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 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
1 site in 1 country.
United States1 site
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
Official title: Pilot Study to Investigate the Safety and Efficacy of Avelumab Monotherapy in Patients With Advanced or Metastatic Adenocarcinoma of the Small Intestine
This is a single-agent, open label, one-arm phase 2 pilot study of avelumab in patients with advanced or metastatic adenocarcinoma of the small intestine.
Read the detailed description
Primary Objectives
- To describe any antitumor activity of avelumab monotherapy, as measured by the response rate in patients with advanced or metastatic small intestinal adenocarcinoma.
- To describe the safety profile of avelumab monotherapy in patients with advanced or metastatic small intestinal adenocarcinoma.
Secondary Objectives
- To determine overall survival, progression-free survival, and duration of response of avelumab monotherapy in patients with advanced small intestinal adenocarcinoma.
- To evaluate the association of tumor PD-L1 and PD-1 expression, MSI status, lymphocytic infiltration, and somatic mutation burden with response.
- Conditions
- Adenocarcinoma
- Being tested
- Avelumab
- Keywords
- small bowel cancer, small bowel carcinoma
- Medical subject headings
- Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
Avelumab through a vein once every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Avelumab Monotherapy | Experimental | Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks. Receives: Drug: Avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate as Measured Using RECIST 1.1
Response rate is the proportion of patients with overall complete (CR) or partial response(PR) among patients with valuable response outcome. Overall response will consider both target and non-target lesions, as well as new lesions.
Target lesions by CT/MRI: CR: Disappearance of all target lesions. PR: >= 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): >= 20% increase in the sum of diameters of target lesions, In addition, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of new lesions. Non-target lesions: CR: Disappearance of all target lesions. Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of applicable tumor marker level above the normal limits. PD: progression of existing non-target lesions.
Measured: Measured every 8 weeks through study completion, an average of 1 year
Number of Patients With Each Worst-Grade Toxicity
To describe the safety profile of avelumab monotherapy in patients with advanced or metastatic small intestinal adenocarcinoma
Measured: On-study date to 30 days following final dose of study drug, or until the event is resolved, stabilized, or determined to be irreversible by the participating investigator if beyond 30 days.
Secondary outcomes (3)
Overall Survival
On study date until death from any cause
Measured: Every 3 months after completing treatment up to 5 years
Progression Free Survival
On-study date until disease progression or death. Progression is >= 20% increase in the sum of diameters of target lesions or non-target lesions, or appearance of new lesions.
Measured: On-study date to lesser of date of progression or date of death from any cause measured up to 3 years after treatment
Duration of Response
Time from tumor response date to disease progression or death for any reason.
Measured: Date of first partial or complete response as defined by RECIST 1.1 criteria to date of recurrence or disease progression up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2016 (estimated)
- Study start3 Mar 2017
- Primary completion3 Aug 2021
- Study completion3 Aug 2021
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), EMD Serono
- Responsible party
- Principal investigator, Dana Cardin, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Dana Cardin, M.D., Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03000179
- Sponsor's protocol ID
- VICC GI 1679
- Status last verified
- Mar 2022
- First submitted
- 6 Dec 2016
- Last updated
- 14 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Investigate the Safety and Efficacy of Avelumab Monotherapy in Patients With Advanced or Metastatic Adenocarcinoma of the Small Intestine
- ClinicalTrials.gov ID
- NCT03000179
- Acronym / sponsor ID
- VICC GI 1679
- Conditions
- Adenocarcinoma
- Keywords
- small bowel cancer, small bowel carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), EMD Serono
- Study start
- 3 Mar 2017 (actual)
- Primary completion
- 3 Aug 2021 (actual)
- Study completion
- 3 Aug 2021 (actual)
- First posted
- 21 Dec 2016 (estimated)
- Results
- Posted 14 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-agent, open label, one-arm phase 2 pilot study of avelumab in patients with advanced or metastatic adenocarcinoma of the small intestine.
Detailed description
Primary Objectives
- To describe any antitumor activity of avelumab monotherapy, as measured by the response rate in patients with advanced or metastatic small intestinal adenocarcinoma.
- To describe the safety profile of avelumab monotherapy in patients with advanced or metastatic small intestinal adenocarcinoma.
Secondary Objectives
- To determine overall survival, progression-free survival, and duration of response of avelumab monotherapy in patients with advanced small intestinal adenocarcinoma.
- To evaluate the association of tumor PD-L1 and PD-1 expression, MSI status, lymphocytic infiltration, and somatic mutation burden with response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Avelumab Monotherapy | Experimental | Drug: AvelumabParticipants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Signed and dated written informed consent.
- Male or female ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Histologically confirmed adenocarcinoma of the small intestine that is advanced (not amenable to surgery) or metastatic (clinical stage IV). For the purposes of this study, ampullary tumors are considered a part of the duodenum and are classified as adenocarcinomas of the small intestine.
- At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria that has not been previously irradiated and which can be followed by CT or MRI.
Key exclusion criteria (30 listed)
- There is no restriction on the number of prior therapies. However, prior therapy with antibody or drug specifically targeting T cell regulatory proteins, including but not limited to the following is not allowed: Prior immunotherapy with IL-2 or IFN-α, or an anti-PD-1 (including nivolumab), anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyteassociated antigen-4 (CTLA-4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Within 28 days before first dose of avelumab: Anti-cancer treatment, major surgery requiring general anesthesia, or the use of any investigational agent.
- Within 14 days before first dose of avelumab: Therapeutic or palliative radiation therapy. (Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab.)
- Current use of immunosuppressive medication, except the following:
- Previous malignant disease other than adenocarcinoma of the small intestine within the last 5 years, with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of avelumab AND additional therapy not required while receiving study treatment).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvelumabAvelumab through a vein once every 2 weeks | Drug | Avelumab Monotherapy |
Primary outcome
Overall Response Rate as Measured Using RECIST 1.1
Time frame: Measured every 8 weeks through study completion, an average of 1 year
Response rate is the proportion of patients with overall complete (CR) or partial response(PR) among patients with valuable response outcome. Overall response will consider both target and non-target lesions, as well as new lesions. Target lesions by CT/MRI: CR: Disappearance of all target lesions. PR: >= 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): >= 20% increase in the sum of diameters of target lesions, In addition, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of new lesions. Non-target lesions: CR: Disappearance of all target lesions. Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of applicable tumor marker level above the normal limits. PD: progression of existing non-target lesions.
Number of Patients With Each Worst-Grade Toxicity
Time frame: On-study date to 30 days following final dose of study drug, or until the event is resolved, stabilized, or determined to be irreversible by the participating investigator if beyond 30 days.
To describe the safety profile of avelumab monotherapy in patients with advanced or metastatic small intestinal adenocarcinoma
3 secondary outcomes
Overall Survival
Time frame: Every 3 months after completing treatment up to 5 years
Progression Free Survival
Time frame: On-study date to lesser of date of progression or date of death from any cause measured up to 3 years after treatment
Duration of Response
Time frame: Date of first partial or complete response as defined by RECIST 1.1 criteria to date of recurrence or disease progression up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dana Cardin, M.D. principal investigator
Vanderbilt-Ingram Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avelumab in people with Adenocarcinoma, run by Vanderbilt-Ingram Cancer Center at 1 site 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 30 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: stopped early, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 14 Apr 2022). 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?
Overall Response Rate as Measured Using RECIST 1.1 (time frame: Measured every 8 weeks through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Apr 2022.