A Study to Evaluate the Safety and Tolerability of MEDI-565 in Adults With Gastrointestinal Adenocarcinomas

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by MedImmune LLC
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01284231
First received: January 18, 2011
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Gastrointestinal Adenocarcinomas
Drug: MEDI-565
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label Study to Evaluate the Safety and Tolerability of MEDI-565 in Adults With Gastrointestinal Adenocarcinomas

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • 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. [ Time Frame: MTD/OBD will be evaluated from the time of first administration of MEDI-565 through the first 28-day cycle ] [ Designated as safety issue: Yes ]
    MTD/OBD will be determined based on Dose Limiting Toxicities that will be evaluated from the time of first administration of MEDI-565 through the first 28-day cycle

  • Evaluate the safety profile in adult subjects with advanced gastrointestinal (GI) adenocarcinomas who have no available standard or curative treatments. [ Time Frame: AEs and SAEs will be reported through 30 days after the last dose of MEDI 565 ] [ Designated as safety issue: Yes ]
    The number (percentage) of subjects with AEs and SAEs reported through 30 days after the last dose of MEDI 565 will be summarized for all subjects who received at least one dose of study drug (Safety Population).


Secondary Outcome Measures:
  • Assess the safety and antitumor activity of MEDI-565 in the dose-expansion phase. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The antitumor activity of MED-565 will be assessed using objective response rate (ORR), time to response (TTR), duration of response (DR), time to progression (TTP), progression‑free survival (PFS), and overall survival (OS) using RECIST guidelines

  • Pharmacokinetics of MEDI-565 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Individual MEDI-565 concentrations will be tabulated by dose cohort along with descriptive statistics. Noncompartmental PK data analysis will be performed for data obtained from each dose cohort with scheduled PK sample collection. If the data allow, descriptive statistics of noncompartmental PK parameters (AUC, Cmax, Tmax, CL, Vd, t½) will be provided.

  • Immunogenicity of MED-565 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The immunogenic potential of MEDI-565 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies.


Estimated Enrollment: 115
Study Start Date: December 2010
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEDI-565 - Dose Escalation
Up to 15 dose-escalation cohorts will be enrolled
Drug: MEDI-565
MEDI-565 will be administered by IV infusion over 3 hours per day for 5 consecutive days every 28 days (1 cycle).
Experimental: MEDI-565 Dose Expansion Arm 1
20 subjects with refractory pancreatic adenocarcinoma will receive MEDI-565 at the maximum tolerated dose or optimum biologic dose
Drug: MEDI-565
20 subjects with refractory pancreatic adenocarcinoma to receive MEDI-565 at the maximum tolerated dose or optimum biologic dose by IV infusion over 3 hours per day for 5 consecutive days every 28 days.
Experimental: MEDI-565 Dose Expansion Arm 2
20 subjects with refractory CRC will receive MEDI-565 at the maximum tolerated dose or optimum biologic dose
Drug: MEDI-565
20 subjects with refractory CRC to receive MEDI-565 at the maximum tolerated dose or optimum biologic dose by IV infusion over 3 hours per day for 5 consecutive days every 28 days.
Experimental: MEDI-565 Dose Expansion Arm 3
Subjects with refractory gastroesophageal cancer will receive MEDI-565 at the maximum tolerated dose or optimum biological dose
Drug: MEDI-565
20 Subjects with refractory Gastroesophageal cancer to receive MEDI-565 at the maximum tolerated dose or optimum biologic dose by IV infusion over 3 hours per day for 5 consecutive days every 28 days.

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 refractory CRC, refractory pancreatic cancer, or refractory gastroesophageal cancer.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • For the dose-expansion phase, subjects must have CRC or pancreatic adenocarcinoma confirmed by prior pathological assessment 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01284231

Contacts
Contact: MedImmune Contact ClinicalTrialEnquiries@Medimmune.com
Contact: Kelly Henson hensonk@medimmune.com

Locations
United States, District of Columbia
Research Site Recruiting
Washington, District of Columbia, United States
United States, Georgia
Research Site Recruiting
Augusta, Georgia, United States
United States, North Carolina
Research Site Recruiting
Durham, North Carolina, United States
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Naimish Pandya, MD MedImmune LLC
  More Information

Additional Information:
No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01284231     History of Changes
Other Study ID Numbers: MI-CP216
Study First Received: January 18, 2011
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
MEDI-565, gastrointestinal adenocarcinomas, carcinoembryonic antigen, bispecific T-cell engager, colorectal cancer, pancreatic cancer, gastroesophageal cancer

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on September 18, 2014