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

Brief Summary

Official Title: “A Phase 1, Open-Label Study to Evaluate the Safety and Tolerability of MEDI-565 in Adults With Gastrointestinal Adenocarcinomas”

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.

  • Study Type: Interventional
  • Study Design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
  • Study Primary Completion Date: August 2017

Detailed Clinical Trial 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.

Interventions Used in this Clinical Trial

  • 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).
  • 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.
  • 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.
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: MEDI-565 – Dose Escalation
    • Up to 15 dose-escalation cohorts will be enrolled
  • 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
  • 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
  • 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

Outcome Measures for this Clinical Trial

Primary 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
      Safety Issue?: Yes
  • 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
      Safety Issue?: Yes

Secondary Measures

  • Assess the safety and antitumor activity of MEDI-565 in the dose-expansion phase.
    • Time Frame: 3 years
      Safety Issue?: No
  • Pharmacokinetics of MEDI-565
    • Time Frame: 3 years
      Safety Issue?: No
  • Immunogenicity of MED-565
    • Time Frame: 3 years
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • MedImmune LLC
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Naimish Pandya, MD, Study Director, MedImmune LLC
  • Overall Contact(s)
    • MedImmune Contact, ClinicalTrialEnquiries@Medimmune.com

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01284231