Clinical trial NCT01284231: A Study to Evaluate the Safety and Tolerability of MEDI-565 in Adults With Gastrointestinal Adenocarcinomas
Official title: A Phase 1, Open-Label Study to Evaluate the Safety and Tolerability of MEDI-565 in Adults With Gastrointestinal Adenocarcinomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastrointestinal Adenocarcinomas
Keywords: MEDI-565, gastrointestinal adenocarcinomas, carcinoembryonic antigen, bispecific T-cell engager
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2011-01-26
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To determine the maximum tolerated dose and/or optimum biologic dose of MEDI-565 in adult subjects and evaluate the safety profile in adult subjects with advanced gastrointestinal adenocarcinomas who have no available standard or curative treatments.

Detailed description: This is a FTIH, dose-escalation and expansion Phase 1 study. The first part is a multicenter, open-label, single-arm, dose-escalation study of MEDI-565 to determine the MTD or OBD and evaluate the safety, tolerability, PK, IM, and antitumor activity of MEDI 565 in adult subjects who have GI adenocarcinomas for which no standard or curative treatments are available. The second part is a dose-expansion study at the MTD or OBD in subjects with selected tumor types.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years of age at the time of screening
* Adequate contraception from screening through end of trial
* For the dose-escalation phase, subjects with GI adenocarcinomas with no available standard or curative treatments
* Adequate hematological function
* Adequate organ function
* For subjects who had prior treatment with chemotherapy, biological therapy, radiotherapy, or had prior surgery: eligible for study entry if at least 30 days have passed since their treatment/surgery
* Life expectancy of at least 3 months
* Karnofsky performance status ≥ 70%
* Body weight ≥ 45 kg

Exclusion Criteria:

* Concurrent enrollment in another clinical study
* Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals
* Prior treatment with MEDI-565
* History of allergy or reaction to any component of the MEDI-565 formulation
* History of malignancy other than GI adenocarcinoma, within 5 years prior to study entry, with the exception of ductal carcinoma in situ of the breast, basal cell carcinoma of the skin or carcinoma in situ of the cervix successfully treated with curative therapy
* Diagnosis of hepatocellular carcinoma
* Clinical history of significant CNS pathology
* Active bacterial infection or known bacteremia.
* Vaccination within 2 weeks prior to initiation of MEDI-565
* Infection with HIV-1 or HIV-2; chronic infection with hepatitis B or C
* History of primary immunodeficiency
* History of chronic autoimmune disease
* Elective surgery planned during the study period through 30 days after discontinuation of MEDI-565.
* Treatment with any chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment within 30 days prior to study entry and not recovered from treatment
* Treatment with any investigational agent within 30 days prior to initiation of MEDI-565
* Regular dose of systemic corticosteroids during the 30 days prior to initiation of MEDI-565 or anticipated need of corticosteroids exceeding prednisone 40 mg/day of prednisone or equivalent during the trial, or any other systemic immunosuppressive therapy within 30 days prior to study entry (some maintenance doses allowed)
* Contraindication to any protocol-specified concomitant medications administered during this study
* Pregnancy or lactation
* Evidence of any uncontrolled systemic disease (other than GI adenocarcinoma)
* Recent history of cardiac disease, including myocardial infarction, unstable angina pectoris or uncontrolled arrhythmia within 6 months, or evidence of severe congestive heart failure
* A marked baseline prolongation of corrected QT interval interval

Primary outcomes:
measure: Determine the maximum tolerable dose (MTD) or optimal biological dose (OBD) of MEDI-565 in subjects with gastrointestinal (GI) adenocarcinomas for which no standard or curative treatments are available.
timeFrame: MTD/OBD will be evaluated from the time of first administration of MEDI-565 through the first 28-day cycle
measure: Evaluate the safety profile in adult subjects with advanced gastrointestinal (GI) adenocarcinomas who have no available standard or curative treatments.
timeFrame: AEs and SAEs will be reported through 30 days after the last dose of MEDI 565
Secondary outcomes:
measure: Assess the safety and antitumor activity of MEDI-565 in the dose-expansion phase.
timeFrame: 3 years
measure: Pharmacokinetics of MEDI-565
timeFrame: 3 years
measure: Immunogenicity of MED-565
timeFrame: 3 years
Other outcomes:
Locations:
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
Study officials:
affiliation: MedImmune LLC
name: Jennifer McDevitt
role: STUDY_DIRECTOR
References: