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A Phase I, Open-Label, Multicentre Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI4736 in Patients With Advanced Solid Tumours

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ClinicalTrials.gov Identifier: NCT01938612
Recruitment Status : Active, not recruiting
First Posted : September 10, 2013
Last Update Posted : June 10, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a phase I, open-label, multicentre study of MEDI4736 administered intravenously with a standard 3+3 dose-escalation phase to evaluate safety, tolerability, and pharmacokinetics in patients with advanced solid tumor followed by an expansion phase in patients with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: MEDI4736 Drug: tremelimumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 269 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Multicentre Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI4736 in Patients With Advanced Solid Tumours
Actual Study Start Date : September 12, 2013
Actual Primary Completion Date : March 1, 2018
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: MEDI4736 Q2W
Evaluate MEDI4736 given every 2 weeks
Drug: MEDI4736
MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.

Experimental: MEDI4736 Q3W
Evaluate MEDI4736 given every 3 weeks
Drug: MEDI4736
MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.

Experimental: MEDI4736 Dose Expansion
evaluate MEDI4736 given every 2 weeks
Drug: MEDI4736
MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.

Experimental: MEDI4736 Q4W
Evaluate MEDI4736 given every 4 weeks
Drug: MEDI4736
MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.

Experimental: MEDI4736 combined with another drug
evaluate MEDI4736 in combination with another drug given every 4 weeks
Drug: tremelimumab
tremelimumab is administered by IV infusion every 4 weeks




Primary Outcome Measures :
  1. Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs) [ Time Frame: 90 days after the last dose of MEDI4736 ]
    Safety profile will be assessed through number of participants experiencing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, and physical examinations.


Secondary Outcome Measures :
  1. Area under the concentration of MEDI4736 time curve [ Time Frame: Up to 90 days after the last dose of MEDI4736 ]
    If data allow, noncompartmental PK parameter (AUC) will be estimated.

  2. Percentage of participants who developed detectable anti-drug antibodies (ADAs). [ Time Frame: Up to 6 months after the last dose of MEDI4736 or up to 1 month after the last dose of tremelimumab where applicable. ]
    The immunogenic potential of MEDI4736 or tremelimumab will be assessed by summarizing the number percentage of subjects who develop detectable anti-drug antibodies (ADAs).

  3. Objective response rate (ORR) [ Time Frame: From first dose of study drug until death or up to 2 years ]
  4. Maximum tolerated dose (MTD) or optimal biological dose (OBD) [ Time Frame: 90 days after the last dose of MEDI4736 ]
    maximum tolerated dose (MTD) or optimal biological dose (OBD) of MEDI4736, if possible

  5. Maximum concentration of MEDI4736 [ Time Frame: Up to 90 days after the last dose of MEDI4736 ]
    If data allow, noncompartmental PK parameter (Cmax) will be estimated.

  6. Clearance [ Time Frame: Up to 90 days after the last dose of MEDI4736 ]
    If data allow, noncompartmental PK parameter (CL) will be estimated.

  7. half-life after administration of MEDI4736 [ Time Frame: Up to 90 days after the last dose of MEDI4736 ]
    If data allow, noncompartmental PK parameter (t½) will be estimated.

  8. Disease control rate (DCR) [ Time Frame: From first dose of study drug until death or up to 2 years ]
  9. Duration of response (DoR) [ Time Frame: From first dose of study drug until death or up to 2 years ]
  10. Progression-free survival (PFS) [ Time Frame: From first dose of study drug until death or up to 2 years ]
    Alive and progression free at 6 months (APF6) and 12 months (APF12) will be obtained using the Kaplan-Meier plot of PFS.

  11. Overall survival (OS) [ Time Frame: From first dose of study drug until death or up to 2 years ]
    The proportion of patients alive at 12 months will be obtained from the Kaplan-Meier plot of OS.



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Ages Eligible for Study:   20 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • In the dose-escalation phase: patients with advanced solid tumors refractory to standard treatment, intolerant of standard treatment, or for which no standard therapy exists.

In the dose-expansion phase: histologically- or cytologically-confirmed advanced or metastatic biliary tract cancer (BTC), esophagus cancer(EC) (squamous cell carcinoma) or squamous cell carcinoma of the head and neck (SCCHN). - men or women. - Eastern Cooperative Oncology Group (ECOG) status of 0 or 1. - Adequate organ and marrow function. - Subjects must have at least 1 measurable lesion. - Available archived tumor tissue sample. - Willingness to provide consent for biopsy samples.

Exclusion Criteria:

  • Any prior Grade ≥ 3 irAE while receiving immunotherapy - Prior exposure to any anti-PD-1 or anti-PD-L1 antibody - Active or prior documented autoimmune disease within the past 2 years - History of primary immunodeficiency - Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment - Women who are pregnant or lactating - Uncontrolled intercurrent illness - Known history of tuberculosis - Known to be human immunodeficiency virus (HIV) positive - Hepatitis B or C infection - Other invasive malignancy within 5 years

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01938612


Locations
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Japan
Research Site
Beppu-shi, Japan, 874-0011
Research Site
Chuo-ku, Japan, 104-0045
Research Site
Kashiwa, Japan, 277-8577
Research Site
Kitaadachi-gun, Japan, 362-0806
Research Site
Koto-ku, Japan, 135-8550
Research Site
Kure-shi, Japan, 737-0023
Research Site
Matsuyama-shi, Japan, 791-0280
Research Site
Nagoya-shi, Japan, 464-8681
Research Site
Osaka-shi, Japan, 541-8567
Research Site
Osakasayama, Japan, 589-8511
Research Site
Sapporo-shi, Japan, 003-0804
Research Site
Sapporo-shi, Japan, 060-8648
Research Site
Suita-shi, Japan, 565-0871
Research Site
Sunto-gun, Japan, 411-8777
Research Site
Takatsuki-shi, Japan, 569-8686
Research Site
Yokohama-shi, Japan, 241-8515
Korea, Republic of
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 135-710
Taiwan
Research Site
Tainan, Taiwan, 704
Research Site
Taipei, Taiwan, 10002
Research Site
Taoyuan, Taiwan, 333
Sponsors and Collaborators
AstraZeneca
Investigators
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Study Director: Robert Iannone, MD AstraZeneca

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01938612     History of Changes
Other Study ID Numbers: D4190C00002
First Posted: September 10, 2013    Key Record Dates
Last Update Posted: June 10, 2019
Last Verified: June 2019

Keywords provided by AstraZeneca:
MEDI4736
Advanced solid tumors
squamous cell carcinoma of the head and Neck
biliary tract cancer
squamous cell carcinoma of esophagus cancer
B7-H1
PD-L1

Additional relevant MeSH terms:
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Neoplasms
Durvalumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs