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A Study of the Safety and Efficacy of Atezolizumab Administered in Combination With Bevacizumab and/or Other Treatments in Participants With Solid Tumors

NCT02715531

Description:

This study will evaluate the safety, efficacy, and pharmacokinetics of atezolizumab in combination with bevacizumab, bevacizumab + oxaliplatin, leucovorin and 5-fluorouracil (5-FU) (FOLFOX), vanucizumab, nab-paclitaxel + gemcitabine, FOLFOX, or 5-FU + cisplatin, in participants with solid tumors.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
  • Hepatocellular Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

A Study of the Safety and Tolerability of <span class="go-doc-concept go-doc-intervention">Atezolizumab</span> Administered in Combination With <span class="go-doc-concept go-doc-intervention">Bevacizumab</span> and/or Other Treatments in Participants With Solid Tumors

Title

  • Brief Title: A Study of the Safety and Tolerability of Atezolizumab Administered in Combination With Bevacizumab and/or Other Treatments in Participants With Solid Tumors
  • Official Title: An Open-Label, Multicenter Phase Ib Study of The Safety and Tolerability of Atezolizumab (Anti-PD-L1 Antibody) Administered in Combination With Bevacizumab And/Or Other Treatments in Patients With Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT02715531

    ORG ID: GO30140

    Trial Conditions

    Solid Tumor

    Trial Interventions

    Drug Synonyms Arms
    5-FU Arm B (Gastric cancer)
    Atezolizumab RO5541267 Arm A (HCC), Arm B (Gastric cancer), Arm C (Metastatic Pancreatic cancer)
    Bevacizumab Arm A (HCC), Arm B (Gastric cancer)
    Gemcitabine Arm C (Metastatic Pancreatic cancer)
    Leucovorin Arm B (Gastric cancer)
    Nab-Paclitaxel Arm C (Metastatic Pancreatic cancer)
    Oxaliplatin Arm B (Gastric cancer)

    Trial Purpose

    This study will evaluate the safety, tolerability and pharmacokinetic variability of
    atezolizumab, in combination with bevacizumab and/or Oxaliplatin, Leucovorin and
    5-Fluorouracil (FOLFOX) at the dose level and schedule indicated for hepatocellular
    carcinoma (HCC) (Arm A) and gastric cancer (Arm B), and in combination with nab-paclitaxel
    and gemcitabine at the dose level and schedule indicated for metastatic pancreatic cancer
    (Arm C).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm A (HCC) Experimental Participants with HCC will receive atezolizumab 1200 milligrams (mg) IV and bevacizumab 15 milligrams per kilogram (mg/kg) IV, every 3 weeks (q3w), each cycle of 21 days, as long as participants are experiencing clinical benefit in the opinion of the investigator. Atezolizumab, Bevacizumab
    Arm B (Gastric cancer) Experimental Participants with HER2 negative adenocarcinoma of the stomach or GEJ will receive atezolizumab 840 mg IV, bevacizumab 10 mg/kg IV, oxaliplatin 85 mg/m^2 IV, leucovorin 200 mg/m^2 or 400 mg/m^2 IV, and 5-FU (400 mg/m^2 administered as an IV bolus, followed by 2400 mg/m^2 administered by continuous IV infusion over 46 [ 1] hours), every 2 weeks (q2w), each cycle of 28 days, as long as participants are experiencing clinical benefit in the opinion of the investigator. 5-FU, Atezolizumab, Bevacizumab, Leucovorin, Oxaliplatin
    Arm C (Metastatic Pancreatic cancer) Experimental Participants with metastatic pancreatic cancer will receive atezolizumab 840 mg IV q2w starting on Day 1, Cycle 1 (each cycle of 28 days), administration of nab-paclitaxel (125 mg/m^2 IV over 30-40 minutes) followed by gemcitabine (1000 mg/m^2 IV over 30-40 minutes) will occur on Days 1, 8, and 15 of each cycle (3-weeks-on/1-week-off schedule). Treatment consisting of atezolizumab with gemcitabine and nab-paclitaxel may be continued as long as participants are experiencing clinical benefit in the opinion of the investigator. Atezolizumab, Gemcitabine, Nab-Paclitaxel

    Eligibility Criteria

    Inclusion Criteria:

    General Inclusion criteria

    - Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version
    (v) 1.1

    - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    - Adequate hematologic and end organ function

    - Resolution of any acute, clinically significant treatment-related toxicity from prior
    therapy to Grade less than or equal to (</=) 1 prior to study entry, with the
    exception of alopecia

    - Ready to use reliable contraceptive procedures

    Inclusion criteria specific to HCC (Arm A):

    - HCC of all subtypes

    - The participant has disease that is not amenable to a curative approach

    - No prior line of systemic therapy (includes participants who are sorafenib-nave)

    - Willing to undergo fresh liver biopsy if provided archival tissue was taken greater
    than (>) 6 months from Cycle 1 Day 1

    - Child-Pugh Score of A

    - Albumin > 3 grams per deciliter (g/dL)

    - Documented virology status of hepatitis, as confirmed by screening hepatitis B
    surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and/or
    antihepatitis C virus (HCV)

    - Antiviral therapy per local standard-of-care if active hepatitis B virus (HBV) or HCV
    infection

    Inclusion criteria specific to Gastric cancer (Arm B)

    - Histologically or cytologically confirmed locally advanced or metastatic
    adenocarcinoma of the stomach or gastroesophageal junction (GEJ) in participants who
    have not received prior systemic therapy for metastatic disease

    - Absence of HER2 expression documented as in situ hybridization (ISH) negative on
    previously collected and assessed tumor tissue upon initial diagnosis of disease.

    Inclusion criteria specific to metastatic pancreatic cancer (Arm C)

    - Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas

    - No previous radiotherapy, surgery, chemotherapy, or investigational therapy for the
    treatment of metastatic disease

    Exclusion Criteria:

    General exclusion criteria

    - Uncontrolled pleural effusion, pericardial effusion, or ascites

    - Uncontrolled tumor-related pain

    - Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of
    bisphosphonate therapy

    - Known clinically significant liver disease, including active viral, alcoholic, or
    other hepatitis, cirrhosis, fatty liver, and inherited liver disease

    - Known primary central nervous system (CNS) malignancy or untreated or active CNS
    metastases

    - Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
    or other recombinant human antibodies

    - Positive test for Human Immunodeficiency Virus (HIV)

    - Active hepatitis B (chronic or acute), or hepatitis C

    - Active tuberculosis

    - Severe infections within 4 weeks prior to Day 1

    - Signs or symptoms of significant infection within 2 weeks prior to Day 1

    - Received oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1 Day 1

    - Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac
    disease (Class II or greater), myocardial infarction within 3 months prior to prior
    to Day 1, unstable arrhythmias, or unstable angina

    - History of stroke, reversible ischemic neurological defect or transient ischemic
    attack within 6 months prior to Day 1

    - Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or
    anticipation that such a live attenuated vaccine will be required during the study

    - Any serious medical condition or abnormality in clinical laboratory tests that, in
    the investigator's judgment, precludes the participant's safe participation in and
    completion of the study

    - Malignancies other than pancreatic carcinoma within 2 years prior to study start,
    with the exception of those with a negligible risk of metastasis or death (e.g.,
    expected 5-year OS >90%) treated with expected curative outcome (such as adequately
    treated carcinoma in situ of the cervix, basal or squamous cell skin cancer,
    localized prostate cancer treated surgically with curative intent, ductal carcinoma
    in situ treated surgically with curative intent)

    Exclusion Criteria Related to Medications

    - Prior treatment with anti- cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-
    programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody

    - Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of
    the drug, whichever is longer, prior to screening

    - Treatment with systemic corticosteroids or other immunosuppressive medications
    (including but not limited to prednisone, cyclophosphamide, azathioprine,
    methotrexate, thalidomide, and anti tumor necrosis factor [TNF] agents) within 2
    weeks prior to Cycle 1, Day 1

    - History of severe allergic, anaphylactic, or other hypersensitivity reactions to
    chimeric or humanized antibodies or fusion proteins

    - Participants with prior allogeneic bone marrow transplantation or prior solid organ
    transplantation

    - Known allergies to oxaliplatin (or other platinum agents), leucovorin, 5-Fluorouracil
    (FU), nab-paclitaxel (or other taxanes) or gemcitabine

    Bevacizumab-Specific Exclusions (Arms A and B)

    - Core biopsy or other minor surgical procedure, excluding placement of a vascular
    access device, within 7 days prior to the first dose of bevacizumab

    - History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation,
    or intra-abdominal abscess within 6 months prior to Day 1

    - Clinical signs or symptoms of GI obstruction or requirement for routine parenteral
    hydration, parenteral nutrition, or tube feeding

    - Evidence of abdominal free air that is not explained by paracentesis or recent
    surgical procedure

    - Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture

    - Proteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour
    urine collection

    - Metastatic disease that involves major airways or blood vessels, or centrally located
    mediastinal tumor masses of large volume

    Exclusions specific to Arm A (HCC)

    - Participants with untreated or incompletely treated varices with bleeding or
    high-risk for bleeding

    - Moderate or severe ascites

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of Participants With At Least One Adverse Event

    Secondary Outcome Measures

    Serum Concentrations of Atezolizumab (Arms A, B and C)

    Serum Concentration of Bevacizumab (Arms A and B)

    Plasma Concentration of Oxaliplatin (Arm B)

    Plasma Concentration of 5-FU (Arm B)

    Serum Concentration of nab-Paclitaxel (Arm C)

    Serum Concentration of Gemcitabine (Arm C)

    Percentage of Participants with Best Overall Response as determined by Response Evaluation Criteria in Solid Tumours (RECIST) Version (v) 1.1

    Percentage of Participants with Objective Response as determined by RECIST v1.1

    Duration of Objective Response as determined by RECIST v1.1

    Progression Free Survival Duration as determined by RECIST v1.1

    Overall Survival Duration

    Trial Keywords