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Study to Assess MEDI4736 With Either AZD9150 or AZD5069 in Advanced Solid Tumors & Relapsed Metastatic Squamous Cell Carcinoma of Head & Neck

This study is currently recruiting participants.
Verified November 2017 by AstraZeneca
Sponsor:
ClinicalTrials.gov Identifier:
NCT02499328
First Posted: July 16, 2015
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
MedImmune LLC
Information provided by (Responsible Party):
AstraZeneca
  Purpose
This multicentre, open-label, Phase 1b/2 study is designed as a 2 part study consisting of a dose-escalation, safety run-in Part A and a dose-expansion Part B

Condition Intervention Phase
Advanced Solid Tumors & Metastatic Squamous Cell Carcinoma of the Head and Neck Drug: AZD9150 Drug: MEDI4736 Drug: AZD5069 Drug: tremelimumab (treme) Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2, Open-Label, Multicentre Study Assessing the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of MEDI4736 in Combination With AZD9150 or AZD5069 in Patients With Advanced Solid Malignancies and Subsequently Comparing AZD9150 and AZD5069 Both as Monotherapy and in Combination With MEDI4736 as Second Line Treatment in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Part A: MTDs (Maximum Tolerated Dose) or recommended doses for dose-expansion [ Time Frame: 35 days ]
    After completion of DLT period (35 days) for the maximum dose cohort. Expected to be achieved within 6 months of first subject dosed

  • Part A: safety and tolerability in terms of adverse events [ Time Frame: At every treatment and follow up visit until disease progression. Expected to be for up to 12 months ]
    Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters

  • Part B: ORR (Objective Response Rate) in patients with IL/2L RM-SCCHN. [ Time Frame: Assessed at every even-numbered cycles with RECIST until disease progression expected to be for up to 12 months. ]
    proportion of patients who have an objective response at a given visit. ORR will be summarised by treatment group


Secondary Outcome Measures:
  • Part A and B: Evaluation of pharmacokinetics, Pharmacodynamics, immunogenecity and translational biomarkers [ Time Frame: during leadin period, and cycles 1 and 2, an average of 1 year ]
  • Part A: Antitumour activity in monotherapy and combination arms of study [ Time Frame: assessed at every even numbered cycle with RECIST until disease progression. Expected to be for a period up to 12 months ]
    complete response, partial response, stable disease or progressive disease based on RECIST

  • Part B: Safety and tolerability in terms of AEs [ Time Frame: At every treatment visit and 28 days after last dose. In patients with MedI4736 for IM (Immunogenicity) 90 days after last dose. ]
  • Part B: Secondary measures change in efficacy [ Time Frame: Assessed at every even-numbered cycles.assessed at every even numbered cycle with RECIST until disease progression. Expected to be for a period up to 12 months ]
    Disease control rate; Duration of overall response; progression-free survival (PFS); overall survival (OS); and proportion of patients alive at 12 months)


Estimated Enrollment: 147
Actual Study Start Date: August 5, 2015
Estimated Study Completion Date: August 29, 2018
Estimated Primary Completion Date: August 29, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A1: AZD9150 / MEDI4736
Patients allocated in cohort of arm A1 (AZD9150/MEDI4736 will be evaluated for DLT until an MTD is achieved.
Drug: AZD9150
AZD9150
Drug: MEDI4736
MEDI4736
Experimental: Part A2: AZD5069 / MEDI4736
Patients allocated in cohort of arm A2 (AZD5069/MEDI4736 will be evaluated for DLT until an MTD is achieved.
Drug: MEDI4736
MEDI4736
Drug: AZD5069
AZD5069
Experimental: Part B1:AZD9150+MEDI4736:PDL1 pretreated
Patients in arm B1 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.
Drug: AZD9150
AZD9150
Drug: MEDI4736
MEDI4736
Experimental: Part B2:AZD5069+MEDI4736:PDL1 pretreated
Patients in arm B2 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.
Drug: MEDI4736
MEDI4736
Drug: AZD5069
AZD5069
Experimental: Part B3: AZD9150+MED4736:naiive 2L
Patients in arm B3 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.
Drug: AZD9150
AZD9150
Drug: MEDI4736
MEDI4736
Experimental: Part B4:AZD5069+MEDI4736:naiive patients
Patients in arm B4 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.
Drug: MEDI4736
MEDI4736
Drug: AZD5069
AZD5069
Experimental: Part B5: AZD9150 in naiive patients
Patients in arm B5 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival
Drug: AZD9150
AZD9150
Experimental: Part B6:AZD5069 in naiive patients
Patients in arm B6 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival
Drug: AZD5069
AZD5069
Experimental: Part A3: AZD5069/MEDI4736
Patients allocated in cohort of arm A3 (AZD5069/MEDI4736) will be evaluated for DLT and viability as alternate dosing option for Phase 2 studies
Drug: MEDI4736
MEDI4736
Drug: AZD5069
AZD5069
Experimental: Part A4: AZD9150/Treme/MEDI4736
Patients allocated in cohort of arm A4 (AZD9150/treme/MEDI4736) will be evaluated for DLT and MTD
Drug: AZD9150
AZD9150
Drug: MEDI4736
MEDI4736
Drug: tremelimumab (treme)
tremelimumab
Experimental: Part A5: AZD5069/Treme/MEDI4736
Patients allocated in cohort of arm A5 (AZD5069/treme/MEDI4736) will be evaluated for DLT and MTD.
Drug: MEDI4736
MEDI4736
Drug: AZD5069
AZD5069
Drug: tremelimumab (treme)
tremelimumab
Experimental: Part A6: AZD9150/MEDI4736
Patients allocated in cohort of arm A6 (AZD9150/MEDI4736) will be evaluated for safety, PK and PD.
Drug: AZD9150
AZD9150
Drug: MEDI4736
MEDI4736
Experimental: Part A7: AZD5069/MEDI4736
Patients allocated in cohort of arm A7 (AZD5069/MEDI4736) will be evaluated for safety, PK and PD.
Drug: MEDI4736
MEDI4736
Drug: AZD5069
AZD5069
Experimental: Part B7: AZD9150+MEDI4736: naiive 1L
Patients in Arm B7 will be evaluated for efficacy until disease progression and then followed up for safety and survival
Drug: AZD9150
AZD9150
Drug: MEDI4736
MEDI4736

Detailed Description:

The dose-escalation Part A of this study will involve patients with advanced solid malignancies refractory to standard therapy or for which no standard of care regimen currently exists. Approximately 30 evaluable patients per treatment arm (A1 or A2) will be enrolled. A3 will test viability of alternate dosing schedule for AZD5069, A4/A5 will evaluate AZD9150/AZD5069 in fixed dose combination with MEDI4736 and tremelimumab in solid tumors. there may also be safety run in cohorts enrolled (A6/A7) in specific solid tumor types (breast and prostate cancer).

Once the maximum tolerated doses (MTDs) for each of the 2 agents (AZD9150/AZD5069)in combination with MEDI4736 have been identified or the maximum doses of each of the 2 agents in combination with MEDI4736 have been reached, the dose expansion Part B of the study would commence. It will be conducted in patients with recurrent and/or metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN). Between 68 and 266 eligible patients will be enrolled and will randomly assigned to 1 of the following 6 treatment arms or non randomized arm B7:

  • Treatment arm B1: AZD9150 in combination with MEDI4736 in patients with prior exposure to anti-PD-(L)1 antibodies
  • Treatment arm B2: AZD5069 in combination with MEDI4736 in patients with prior exposure to anti-PD-(L)1 antibodies
  • Treatment arm B3: AZD9150 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies (2L RM SCCHN)
  • Treatment arm B4: AZD5069 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies
  • Treatment arm B5: AZD9150 alone in patients with no prior exposure to anti-PD-(L)1 antibodies
  • Treatment arm B6: AZD5069 alone in patients with no prior exposure to anti-PD-(L)1 antibodies
  • Treatment arm B7 (non randomized): AZD9150 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies (1L RM SCCHN)
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male and female patients must be at least 18 years of age.
  • Has an Eastern Cooperative Oncology Group (ECOG) PS score of 0 or 1.
  • Has measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) with a minimum size of 10 mm by computerised tomography (CT) scan, except lymph nodes which must have minimum short axis size of 15 mm (CT scan slice thickness no greater than 5 mm in both cases). Indicator lesions must not have been previously treated with surgery, radiation therapy, or radiofrequency ablation unless there is documented progression after therapy.
  • Has undergone ≤3 previous regimens (depending on treatment arm) of cytoreductive therapies including, but not limited to, platinum-based compounds, taxanes, or 5-fluorouracil. for B7, no prior systemic treatments should have been received for RM SCCHN
  • Adequate organ and marrow function
  • Female subjects of childbearing potential and male subjects with partners of childbearing potential should ensure use of a highly effective method of birth control as defined in study protocol
  • Additional inclusion for part A: Has a histological confirmation of a solid malignancy (other than HCC) that is refractory to standard therapy or for which no standard of care regimen currently exists.
  • Addition inclusion for Part A (A6 & A7) Has a histological confirmation of either metastatic breast (ER+ve for Arm A6, 50% ER +ve and 50% HER2+ve metastatic breast cancer patients for Arm A7) or castrate-resistant prostate cancer
  • Additional inclusion for Part B:Has histologically and/or cytologically confirmed SCCHN that is RM and not amendable to curative therapy by surgery or radiation. Squamous cell carcinoma of the head and neck originating from the following sites is eligible: oral cavity, oropharynx, larynx, or hypopharynx. Has at least 1 SCCHN tumour lesion (TL) amenable to biopsy and must have failed, refused, or has been found to be ineligible for least 1 prior platinum-based chemotherapy for RM-SCCHN Additional inclusion criteria for Arms B1 & B2:must have had prior exposure to anti PDL-1 antibody
  • Arms B1-B6: Has undergone 1-3 previous regimens of cytoreductive chemo-therapies Arm B7: with no prior exposure to anti-PD-(L)1 therapies and have received no prior systemic treatment for RM SCCHN

Key Exclusion Criteria:

  • Spinal cord compression unless asymptomatic and not requiring steroids for at least 4 weeks before the start of study treatment. - Presently has a second malignancy other than SCCHN, or history of treatment for invasive cancer other than SCCHN in the past 3 years. Exceptions are
  • Previously treated in-situ carcinoma (ie, noninvasive)
  • Cervical carcinoma stage 1B or less
  • Noninvasive basal cell and squamous cell skin carcinoma Radically treated prostate cancer (prostatectomy or radiotherapy) with normal prostate-specific antigen, and not requiring ongoing antiandrogen hormonal therapy
  • Patients must have completed any previous cancer-related treatments before enrolment. Any concurrent chemotherapy [Chemotherapy washout within 21 days or 5 half-lives (whichever is shorter) from enrolment], radiotherapy, immunotherapy, or biologic, or hormonal therapy for cancer excludes the patient (concurrent use of hormones for noncancer-related conditions [eg, insulin for diabetes and hormone replacement therapy] is acceptable),
  • Experiencing CTCAE grade >1 events, experienced immune-related grade ≥3AEs with prior immunotherapy
  • Has active or prior autoimmune disease within the past 2 years
  • Has active or prior inflammatory bowel disease or primary immunodeficiency
  • Undergone an organ transplant that requires use of immunosuppressive treatment
  • Abnormalities in rhythm, conduction or morphology of resting 12-lead ECG
  • uncontrolled comorbid conditions
  • Received a live attenuated vaccine within 28 days of first study dose, unable to take oral medications
  • History of allergic reactions to study compounds or excepients Additional exclusion criteria Part A: Patients with clinically active brain metastases and prior exposure to AZD9150, AZD5069, MEDI4736, or any other anti PD (L)1 antibody.

Additional exclusion criteria Part B: Patients with brain metastases (known or suspected) Additional exclusion criteria Part B: treatment arms B3, B4, B5, and B6, B7: prior exposure to AZD9150, AZD5069, MEDI4736, or any other anti PD (L)1 antibody.

  Contacts and Locations
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): NCT02499328


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: Cancer Study Locator 877 400 4656 AstraZeneca@emergingmed.com

  Show 67 Study Locations
Sponsors and Collaborators
AstraZeneca
MedImmune LLC
Investigators
Principal Investigator: Dr David Hong, MD M.D. Anderson Cancer Center
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02499328     History of Changes
Other Study ID Numbers: D5660C00004
First Submitted: June 18, 2015
First Posted: July 16, 2015
Last Update Posted: November 17, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
Carcinoma of the Head and Neck

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Antibodies, Monoclonal
Tremelimumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents