Safety and Efficacy of Avelumab in Small Intestinal Adenocarcinoma

NCT03000179 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: VICC GI 1679
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Adenocarcinoma

Keywords

small bowel cancer, small bowel carcinoma

Outcome Measures

Primary Outcomes (2)

• 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 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

  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

  Every 3 months after completing treatment up to 5 years

• Progression Free Survival

  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

  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

Study Arms (1)

Avelumab Monotherapy

EXPERIMENTAL

Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.

Drug: Avelumab

Interventions

Avelumab DRUG

Avelumab through a vein once every 2 weeks

Avelumab Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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;
• 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).

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• EMD Serono: collaborator

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Adenocarcinoma

Interventions

avelumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Teresa Melton
• Organization: Vanderbilt-Ingram Cancer Center

teresa.melton@vumc.org

615-936-7423

Study Officials

• Dana Cardin, M.D.

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 6, 2016
• First Posted: December 21, 2016
• Study Start: March 3, 2017
• Primary Completion: August 3, 2021
• Study Completion: August 3, 2021
• Last Updated: April 14, 2022
• Results First Posted: April 14, 2022

Record last verified: 2022-03

Locations

US (1)