Clinical Trial - NCT02734004

A Phase I/II Study of MEDI4736 in Combination With Olaparib in Patients With Advanced Solid Tumors.

Recruiting

Sponsor: AstraZeneca

Collaborators: IQVIA (formerly QuintilesIMS)

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02734004

Protocol Info

Short Description: MEDI4736 + Olaparib in Advanced Solid Tumors (MEDIOLA)
Long Description: A Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination with Olaparib (PARP inhibitor) in Patients with Advanced Solid Tumors
MGH Status: Open
Sponsor: Astra Zeneca
Disease Program: GYN

Next Steps


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Purpose

The purpose of this study is to look at the effectiveness, safety, and antitumor activity of study drugs MEDI4736 in combination with olaparib (modules 1, 2, 3, 4, 5 and 7, 8 and 9) and MEDI4736 in combination with olaparib and bevacizumab (module 6 and 10). It will also examine what happens to the study drugs in the body and investigate how well the combination between MEDI4736, olaparib and bevacizumab is tolerated.
Condition Title Intervention Phase
Ovarian Breast SCLC Gastric Cancers Olaparib MEDI4736 Bevacizumab Phase 1/Phase 2
Study Type Interventional
Official Title A Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination With Olaparib (PARP Inhibitor) in Patients With Advanced Solid Tumors

Primary Outcome Measures

Disease control rate (DCR) [Complete response + Partial response + Stable disease (CR+PR+SD)] based on RECIST 1.1 [Time Frame: At 12 weeks, compared to Baseline] [Designated as safety issue: ]

The safety and tolerability of MEDI4736 in combination with olaparib (±bevacizumab) by assessment of the number and grade of adverse events [Time Frame: From screening up to 90 days after end of treatment] [Designated as safety issue: ]

The safety and tolerability of MEDI4736 in combination with olaparib (±bevacizumab) by assessment of physical examination [Time Frame: From screening up to 30 days after end of treatment] [Designated as safety issue: ]

The safety and tolerability of MEDI4736 in combination with olaparib (±bevacizumab) by assessment of vital signs [Time Frame: From screening up to 30 days after end of treatment] [Designated as safety issue: ]

The safety and tolerability of MEDI4736 in combination with olaparib (±bevacizumab) by assessment of blood samples [Time Frame: From screening up to 90 days after end of treatment] [Designated as safety issue: ]

ORR (CR + PR) based on RECIST 1.1, and as determined by investigator [Time Frame: RECIST assessments performed at baseline and every 8 wks relative to baseline up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

Disease control rate (DCR) [Complete response + Partial response + Stable disease (CR+PR+SD)] based on RECIST 1.1 [Time Frame: At 24 weeks, compared to Baseline] [Designated as safety issue: ]

DCR (CR+PR+SD) based on RECIST 1.1 [Time Frame: at 16 weeks, compared to Beaseline] [Designated as safety issue: ]


Secondary Outcome Measures

PD-L1 expression in serum samples [Time Frame: Each cycle = 28 days in combination of treatment. Day 1 of cycle 1; Day 15 of cycle 1; Day 1 of cycle 3; Day 1 of cycle 5; Day 1 of cycle 7; 3 month Follow-up visit] [Designated as safety issue: ]

Disease control rate (DCR) [Complete response + Partial response + Stable disease (CR+PR+SD)] based on RECIST 1.1 [Time Frame: At 28 weeks, compared to Baseline] [Designated as safety issue: ]

Time to study treatment discontinuation (TDT) [Time Frame: From Cycle 1, Day 1 until treatment discontinuation from any cause or until death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

Overall Survival (OS) [Time Frame: From Cycle 1, Day 1 until death from any cause, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

Percentage change from baseline in tumor size [Time Frame: At 12 weeks and 28 weeks compared to Baseline] [Designated as safety issue: ]

Best percentage change from baseline in tumor size [Time Frame: From Baseline, at 4 weeks (Modules 1, 2, 3 and 4) and every 8 weeks up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

Serum concentrations of anti-drug antibody (ADA) [Time Frame: Each cycle = 28 days in combination of treatment. Day 1 of cycle 1; Day 15 of cycle 1; Day 1 of cycle 3; Day 1 of cycle 5; Day 1 of cycle 7; 3 month Follow-up visit] [Designated as safety issue: ]

Olaparib pharamacokinetic sample [Time Frame: Olaparib Run-In treatment week 1 day 1; Olaparib Run-In treatment week 4 day 1; Day 15 of Cycle 1] [Designated as safety issue: ]

MEDI4736 pharmacokinetic sample [Time Frame: Each cycle = 28 days in combination of treatment. Day 1 of cycle 1; Day 15 of cycle 1; Day 1 of cycle 3; Day 1 of cycle 5; Day 1 of cycle 7; 3 month Follow-up visit] [Designated as safety issue: ]

Objective response rate (Complete response+Partial response) based on RECIST 1.1 [Time Frame: From Baseline, at 8 weeks and every 8 weeks up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

Duration of response based on RECIST 1.1 [Time Frame: From Baseline, at 8 weeks and every 8 weeks up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

PFS based on RECIST 1.1 [Time Frame: From Baseline, at 8 weeks and every 8 weeks up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

Percentage change from baseline in tumor size [Time Frame: At 24 weeks and 56 weeks compared to Baseline] [Designated as safety issue: ]

Objective response rate (Complete response+Partial response) based on RECIST 1.1 [Time Frame: From Baseline, at 8 weeks and every 8 weeks up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

Duration of response based on RECIST 1.1 [Time Frame: From Baseline, at 8 weeks and every 8 weeks up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

PFS based on RECIST 1.1 [Time Frame: From Baseline, at 8 weeks and every 8 weeks up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

Disease control rate (DCR) [Complete response + Partial response + Stable disease (CR+PR+SD)] based on RECIST 1.1 [Time Frame: At 24 weeks and 56 weeks, compared to Baseline] [Designated as safety issue: ]

Disease control rate (DCR) [Complete response + Partial response + Stable disease (CR+PR+SD)] based on RECIST 1.1 [Time Frame: At 56 weeks, compared to Baseline] [Designated as safety issue: ]

Bevacizumab pharmacokinetic sample [Time Frame: Each cycle = 28 days in combination of treatment. Day 1 of cycle 1; Day 1 of cycle 2; Day 1 of cycle 4; Day 1 of cycle 7] [Designated as safety issue: ]

Objective response rate (Complete response+Partial response) based on RECIST 1.1 [Time Frame: From Baseline, at 4 weeks and every 8 weeks up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

Duration of response based on RECIST 1.1 [Time Frame: From Baseline, at 4 weeks and every 8 weeks up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

PFS based on RECIST 1.1 [Time Frame: From Baseline, at 4 weeks and every 8 weeks up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until all patients receiving IP have completed 104 weeks of treatment.] [Designated as safety issue: ]

Disease control rate (DCR) [Complete response + Partial response + Stable disease (CR+PR+SD)] [Time Frame: 16 weeks and 24 weeks] [Designated as safety issue: ]

Disease control rate (DCR) [Complete response + Partial response + Stable disease (CR+PR+SD)] [Time Frame: 24 weeks] [Designated as safety issue: ]

Olaparib plasma concentrations [Time Frame: Each cycle - 28 days; Day 15 of Cycle 1] [Designated as safety issue: ]

MEDI4736 serum concentrations [Time Frame: Each cycle = 28 days; Day 1 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 4, Day of Cycle 7 (Modules 8, 9 and 10)] [Designated as safety issue: ]

Bevacizumab serum concentrations [Time Frame: Each cycle = 28 days; Day 1 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 4, Day of Cycle 7 (Module 10)] [Designated as safety issue: ]

MEDI4736 ADA (Anti-drug Antigen) serum concentrations [Time Frame: Each cycle = 28 days; Day 1 of Cycle 1, Day 1 of Cycle 4, Day of Cycle 7 (Modules 8, 9 and 10)] [Designated as safety issue: ]

Bevacizumab ADA (Anti-drug Antigen) serum concentrations [Time Frame: Each cycle = 28 days; Day 1 of Cycle 1, Day 1 of Cycle 4, Day of Cycle 7 (Module 10)] [Designated as safety issue: ]

Estimated Enrollment: 427
Study Start Date: March 2016
Estimated Study Completion Date: August 2022
Estimated Primary Completion Date: August 2022
Arms Assigned Interventions

Experimental:Arm 1

Includes initial stage cohorts (modules 1 to 4): Olaparib twice daily starting on week 1 day 1 and MEDI4736 every 4 weeks starting on week 5 day 1
Drug:MEDI4736
MEDI4736

Experimental:Arm 2

Includes 2nd stage cohorts (modules 5&7) and 3rd stage cohorts (modules 8&9): Olaparib twice daily starting on week 1 day 1 and MEDI4736 every 4 weeks starting on week 1 day 1

Experimental:Arm 3

Includes 2nd stage cohort (module 6) and 3rd stage cohort (module 10): Olaparib twice daily starting on week 1 day 1 / MEDI4736 every 4 weeks starting on week 1 day 1 / Bevacizumab every 2 weeks starting on week 1 day 1
Drug:Bevacizumab
Bevacizumab

Eligibility

Ages Eligible for Study: 130 Years-130 Years

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion criteria:

  • Patients must have histologically or cytologically confirmed progressive advanced or metastatic solid tumor of one of the following:
  • Platinum sensitive relapsed small cell lung cancer (module 1)
  • gBRCAm HER2-negative metastatic breast cancer (module 2)
  • gBRCAm ovarian cancer (modules 3 and 5)
  • Metastatic or relapsed Gastric cancer (adenocarcinoma) (module 4)
  • gBRCAm negative ovarian cancer (modules 6 and 7)
  • BRCAm (including germline and tumor BRCA1/2 mutations) human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with metastatic or locally advanced disease, which is unresectable (or the patient is not a candidate for resection) (Module 8 BRCAm)
  • Human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with metastatic or locally advanced disease, which is unresectable (or the patient is not a candidate for resection) Patients must have documented evidence from Myriad central tumor testing that they do not have a mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) and do have a deleterious or suspected deleterious mutation in at least 1 of the following 13 HRR genes: ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L. (Module 9 HRRm).
  • Breast cancer patients with metastatic or locally advanced disease, which is unresectable (or the patient is not a candidate for resection). Patients must have documented evidence from Myriad central tumor testing that they do not have any mutation in BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) (Module 10 TNBC).
  • At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (or magnetic resonance imaging [MRI] suitable for assessment as per RECIST 1.1. The baseline scan must be obtained within 28 days prior to the first dose of olaparib.
  • Male or female patients, age ≥18 years (≥19 years for South Korea)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Life expectancy ≥12 weeks
  • Adequate organ and marrow function
  • Ability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation. Patients should not have gastrointestinal illnesses that would preclude the absorption of olaparib, which is an oral agent. For the gastric cancer cohort, patients with a full or partial gastrectomy will be permitted.
  • Ability of patient to understand and the willingness to sign a written informed consent document prior to any protocol related procedures, including screening evaluations.
  • Female patients must either:
  • Be of non-reproductive potential OR
  • Have a negative serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on Day 1, and agree to use contraception if they or their partner are of reproductive potential

Exclusion criteria

  • Prior chemotherapy or other systemic anticancer therapy within 4 weeks prior to start of olaparib treatment, 6 weeks for nitrosoureas or mitomycin. Exceptions include: Anti-hormonal treatment for ER positive or PR positive breast cancer is allowed until 7 days prior to treatment with olaparib, exposure to an investigational agent within 30 days or 5 half-lives (whichever is the longer) prior to start of olaparib treatment is not allowed, prior receipt of biologics targeting T cell co-regulatory proteins and/or immune checkpoints is not allowed. Examples include MEDI4736 or other PD1 or PD-L1 or PD-L2 inhibitors or anti-CTLA4 therapy, previous treatment with a PARP inhibitor, is not allowed.
  • Radiation therapy within 4 weeks prior to start of olaparib treatment (includes radiation targeting bone metastases) or radionuclide treatment within 6 weeks of treatment start.
  • Current dependency on total parenteral nutrition or IV fluid hydration.
  • Concomitant use of known strong cytochrome P450 (CYP) 3A (CYP3A) inhibitors or moderate CYP3A inhibitors. Concomitant use of known strong or moderate CYP3A inducers.
  • Concomitant therapy with any other anticancer therapy or chronic use of systemic corticosteroids.
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation
  • Whole blood transfusions in the last 120 days
  • Patients with symptomatic or uncontrolled brain metastases.
  • Patients being considered at poor medical risk due to a serious, uncontrolled medical disorder or non-malignant systemic disease.
  • Any psychiatric disorder that prohibits obtaining informed consent
  • Major surgery or significant traumatic injury within 2 weeks of run-in
  • Immunocompromised patients
  • QTc prolongation >470 msec or other significant ECG abnormality noted within 14 days of treatment
  • Pregnant and breastfeeding women are excluded.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  • Previous enrolment in the present study
  • Participation in a clinical study within 28 days or 5 half-lives of the drug, whichever is longer.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02734004

Locations

  • United States, Arizona
    • Research Site Scottsdale, Arizona, United States, 85258
  • United States, Georgia
    • Research Site Newnan, Georgia, United States, 30265
  • United States, Maryland
    • Research Site Towson, Maryland, United States, 21204
  • United States, Massachusetts
    • Research Site Boston, Massachusetts, United States, 02114
    • Research Site Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • Research Site Detroit, Michigan, United States, 48202
  • United States, Missouri
    • Research Site Saint Louis, Missouri, United States, 63110
  • United States, Ohio
    • Research Site Hilliard, Ohio, United States, 43026
  • United States, Pennsylvania
    • Research Site Philadelphia, Pennsylvania, United States, 19104
  • United States, Texas
    • Research Site San Antonio, Texas, United States, 78229
    • Research Site San Antonio, Texas, United States, 78240
  • United States, Wisconsin
    • Research Site Milwaukee, Wisconsin, United States, 53226-3596
  • France,
    • Research Site Bordeaux Cedex, , France, 33076
    • Research Site Caen Cedex 05, , France, 14076
    • Research Site Clermont Ferrand cedex 01, , France, 63011
    • Research Site Dijon cedex, , France, 21079
    • Research Site Lille Cedex, , France, 59020
    • Research Site Marseille CEDEX 5, , France, 13385
    • Research Site Nantes, , France, 44202
    • Research Site Paris cedex 14, , France, 75679
    • Research Site Pierre Benit Cedex, , France, 69495
    • Research Site Toulouse Cedex 9, , France, 31059
    • Research Site Villejuif Cedex, , France, 94805
  • Israel,
    • Research Site Haifa, , Israel, 3109601
    • Research Site Jerusalem, , Israel, 91031
    • Research Site Petah Tikva, , Israel, 49100
    • Research Site Ramat Gan, , Israel, 5265601
    • Research Site Tel Aviv, , Israel, 6423906
  • Korea, Republic of,
    • Research Site Goyang-si, , Korea, Republic of, 10408
    • Research Site Seongnam-si, , Korea, Republic of, 13620
    • Research Site Seoul, , Korea, Republic of, 03080
    • Research Site Seoul, , Korea, Republic of, 03722
    • Research Site Seoul, , Korea, Republic of, 05505
    • Research Site Seoul, , Korea, Republic of, 06273
    • Research Site Seoul, , Korea, Republic of, 06591
    • Research Site Seoul, , Korea, Republic of, 135-710
  • Netherlands,
    • Research Site Amsterdam, , Netherlands, 1066 CX
    • Research Site Amsterdam, , Netherlands, 1081 HV
    • Research Site Maastricht, , Netherlands, 6202 AZ
    • Research Site Nijmegen, , Netherlands, 6525 GA
    • Research Site Rotterdam, , Netherlands, 3075 EA
    • Research Site Utrecht, , Netherlands, 3584 CX
  • Switzerland,
    • Research Site Chur, , Switzerland, CH-7000
    • Research Site Lausanne, , Switzerland, 1011
  • United Kingdom,
    • Research Site Cambridge, , United Kingdom, CB2 0QQ
    • Research Site Dundee, , United Kingdom, DD1 9SY
    • Research Site Glasgow, , United Kingdom, G12 0YN
    • Research Site Greater London, , United Kingdom, SW3 6JJ
    • Research Site London, , United Kingdom, NW1 2PG
    • Research Site London, , United Kingdom, SE1 9RY
    • Research Site Manchester, , United Kingdom, M20 4BX
    • Research Site Newcastle Upon Tyne, , United Kingdom, NE7 7DN
    • Research Site Sutton, , United Kingdom, SM2 5PT

Sponsors and Collaborators

AstraZeneca

IQVIA (formerly QuintilesIMS)

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02734004
Other Study ID Numbers: 2015-004005-16
Study First Received:
Last Updated:
Health Authority:

Keywords provided by AstraZeneca:

MEDIOLA

Olaparib

MEDI4736

Bevacizumab

Ovarian cancer

Breast cancer

Small Cell Lung Cancer

Gastric Cancer

Phase I/II, Adults

PDL-1

Additional relevant MeSH terms:

Stomach Neoplasms

Bevacizumab

Durvalumab

Olaparib

Antibodies, Monoclonal

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019