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A Study to Assess the Safety and Tolerability of MPDL3280A in Combination With Other Immune-modulating Therapies in Patients With Locally Advanced or Metastatic Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02174172
First received: June 19, 2014
Last updated: January 12, 2017
Last verified: January 2017
  Purpose
This global, multicenter, open-label study will evaluate the safety and tolerability of MPDL3280A in combination with other immune-modulating therapies in the treatment of selected advanced or metastatic malignancies. The MPDL3280A plus ipilimumab arm (Arm A) will focus primarily on patients with advanced or metastatic NSCLC. The MPDL3280A plus interferon alfa-2b arm (Arm B) will enroll patients with advanced or metastatic RCC and melanoma. MPDL3280A will be administered intravenously every 3 weeks (q3w).

Condition Intervention Phase
Solid Cancers
Drug: Interferon alfa-2b
Drug: Ipilimumab
Drug: MPDL3280A [TECENTRIQ]
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE I STUDY OF THE SAFETY AND PHARMACOLOGY OF MPDL3280A ADMINISTERED WITH IPILIMUMAB OR INTERFERON-ALPHA IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to 21 days from the first MPDL3280A treatment ]
  • Incidence of adverse events (AEs) [ Time Frame: Up to 30 days after last dose of study drug ]

Secondary Outcome Measures:
  • Best overall response, as determined by investigator assessment using conventional RECIST v1.1 and modified RECIST criteria [ Time Frame: From first study treatment to disease progression, assessed up to 3 years ]
  • Duration of objective response [ Time Frame: From first occurrence of a documented objective response to the time of progression or death from any cause, assessed up to 3 years ]
  • Overall survival [ Time Frame: From first study treatment to death, assessed up to 3 years ]
  • Progression-free survival [ Time Frame: From first study treatment to first occurence of disease progression or death, assessed up to 3 years ]
  • Objective response (partial response plus complete response), confirmed by repeat assessments >/= 4 weeks after initial documentation and determined by investigator assessment using conventional RECIST v1.1 and modified RECIST criteria [ Time Frame: From first study treatment to disease progression, assessed up to 3 years ]
  • Serum concentrations of study drugs, MPDL3280A and ipilimumab administered in combination [ Time Frame: Up to 90 days ]
  • Serum concentrations of study drugs, MPDL3280A and interferon alfa-2b administered in combination [ Time Frame: Up to 90 days ]

Estimated Enrollment: 200
Study Start Date: August 2014
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: MPDL3280A + ipilimumab Drug: Ipilimumab
Ipilimumab IV, single dose, or multiple-dose regimen every Q3W for up to 4 cycles
Drug: MPDL3280A [TECENTRIQ]
MPDL3280A administered intraveneously (IV) every three weeks (q3w)
Experimental: Arm B: MPDL3280A + interferon alfa-2b Drug: Interferon alfa-2b
Interferon alfa-2b administered subcutaneously every other day for up to 3 doses per week
Drug: MPDL3280A [TECENTRIQ]
MPDL3280A administered intraveneously (IV) every three weeks (q3w)

  Eligibility

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

Inclusion Criteria:

  • Age >/= 18 years
  • Histologically or cytologically documented locally advanced or metastatic solid tumors meeting the following study drug-specific criteria:

Inclusion criteria specific to Arm A: MPDL3280A + ipilimumab

  • Escalation stage: NSCLC patients
  • Expansion stage: NSCLC patients
  • Mandatory biopsy cohort: NSCLC or melanoma patients
  • Prior MPDL3280A-treated cohort: NSCLC or melanoma patients

Inclusion criteria specific to Arm B: MPDL3280A + interferon alfa-2b

  • Escalation stage: RCC or melanoma patients
  • Expansion stage: RCC or melanoma patients
  • Mandatory biopsy cohort: RCC or melanoma patients
  • Prior MPDL3280A-treated cohort: RCC or melanoma patients

Inclusion criteria specific to prior MPDL3280A-treated cohorts

Patients who have previously received MPDL3280A as monotherapy or in combination with other agents (except those outlined as exclusions) are eligible if they meet the following criteria:

  • Radiologic evidence of progression after having derived stable disease, partial response, or complete response; patients without evidence of clinical benefit may be enrolled only after approval by the Medical Monitor.
  • Minimum of 21 days from the last dose of MPDL3280A
  • No permanent discontinuation of MPDL3280A due to a treatment-related adverse event
  • Recovery from all MPDL3280A-related adverse events to Grade </= 1 or baseline at the time of consent
  • No history of Grade >/= 3 immune-related adverse events from MPDL3280A, of Grade >/= 3 elevated total bilirubin, of usage of additional immunosuppression or ongoing use of > 10 mg prednisone or corticosteroid dose-equivalent.
  • Disease progression during or after at least one previous systemic, anti-cancer treatment for locally advanced or metastatic NSCLC and RCC
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Life expectancy >/= 12 weeks
  • Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Adequate hematologic and end organ function as confirmed by laboratory results within 14 days prior to the first study treatment
  • For women who are not postmenopausal or surgically sterile and for men with partners of childbearing potential, the agreement to remain abstinent or to use single or combined contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 6 months after the last dose of study drug.

Exclusion Criteria:

General Medical Exclusions:

  • Pregnant and lactating women
  • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment, with the following exception: (1) hormone-replacement therapy or oral contraceptives; (2) tyrosine kinase inhibitors (TKIs) that have been discontinued > 7 days prior to Cycle 1, Day 1, baseline scans must be obtained after discontinuation of prior TKIs
  • Investigational therapy within 28 days prior to initiation of study treatment
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of the MPDL3280A formulation
  • History of or active autoimmune disease
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • History of human immunodeficiency virus (HIV)
  • Patients with active hepatitis B
  • Patients with active hepatitis C
  • Patients with active tuberculosis
  • Any serious medical condition, physical examination finding, or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

Cancer-Specific Exclusions:

  • NSCLC with sensitizing mutations in EGFR or ALK rearrangements
  • Melanoma with BRAF mutations
  • Active or untreated central nervous system (CNS) metastases, as determined by CT or MRI evaluation during screening and prior radiographic assessments
  • Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >/= 2 weeks prior to screening
  • Leptomeningeal disease
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently); patients with indwelling catheters are allowed.
  • Uncontrolled/unstable tumor-related pain
  • Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
  • History of other malignancy within 2 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, localized prostate cancer treated with curative intent, ductal carcinoma in situ treated surgically with curative intent, or other cancers with a similar outcome

Exclusion Criteria Related to Medications:

  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies (Note: Patients who enroll in the prior MPDL3280A-treated cohorts will have previously received MPDL3280A)
  • Treatment with systemic immunostimulatory agents within four weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1 (the use of inhaled corticosteroids and mineralocorticoids is allowed)

Exclusion Criteria Specific to Arm B (MPDL3280A + Interferon Alfa-2b):

  • History of depression, suicidal ideation or behavior, bipolar disorder, or psychosis
  • Hypersensitivity to interferon alpha or any component of the product
  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: NCT02174172

Contacts
Contact: Reference Study ID Number: GO29322 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
United States, Arizona
Pinnacle Oncology Hematology Recruiting
Scottsdale, Arizona, United States, 85258
Mayo Clinic- Scottsdale Recruiting
Scottsdale, Arizona, United States, 85259
United States, California
UCLA Recruiting
Los Angeles, California, United States, 90095
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
Mayo Clinic-Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
United States, Tennessee
Sarah Cannon Research Inst. Recruiting
Nashville, Tennessee, United States, 37203
Netherlands
The Netherlands Cancer Insitute of Amsterdam Recruiting
Amsterdam, Netherlands, 1066 CX
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02174172     History of Changes
Other Study ID Numbers: GO29322
2014-000812-33 ( EudraCT Number )
Study First Received: June 19, 2014
Last Updated: January 12, 2017

Additional relevant MeSH terms:
Interferons
Interferon-alpha
Antibodies, Monoclonal
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 24, 2017