Clinical Trials /

Cobimetinib and Atezolizumab in Treating Participants With Advanced or Refractory Rare Tumors

NCT03108131

Description:

This phase II trial studies how well cobimetinib and atezolizumab work in treating participants with rare tumors that have spread to other places in the body or that does not respond to treatment. Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cobimetinib and atezolizumab may work better in treating participants with advanced or refractory rare tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Cobimetinib and Atezolizumab in Treating Participants With Advanced or Refractory Rare Tumors
  • Official Title: A Phase II, Open-Label, Single-Arm, Multi-Cohort, Proof-of-Principle Study to Investigate the Efficacy of Cobimetinib and Atezolizumab in Advanced Rare Tumors

Clinical Trial IDs

  • ORG STUDY ID: 2016-0869
  • SECONDARY ID: NCI-2018-01399
  • SECONDARY ID: 2016-0869
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03108131

Conditions

  • Locally Advanced Malignant Neoplasm
  • Metastatic Malignant Neoplasm
  • Rare Lesion
  • Rare Neoplastic Syndrome
  • Refractory Malignant Neoplasm
  • Skin Squamous Cell Carcinoma
  • Unresectable Malignant Neoplasm

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (cobimetinib, atezolizumab)
CobimetinibCotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518Treatment (cobimetinib, atezolizumab)

Purpose

This phase II trial studies how well cobimetinib and atezolizumab work in treating participants with rare tumors that have spread to other places in the body or that does not respond to treatment. Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cobimetinib and atezolizumab may work better in treating participants with advanced or refractory rare tumors.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the efficacy of cobimetinib plus atezolizumab (COTEZO) in cohorts of advanced
      rare tumors using objective response rate (ORR) per Response Evaluation Criteria in Solid
      Tumors (RECIST) version (v)1.1.

      SECONDARY OBJECTIVES:

      I. To determine objective response rate (ORR) per immune-related RECIST (irRECIST) criteria.

      II. To determine progression-free survival (PFS) on COTEZO in cohorts of advanced rare tumors
      per RECIST v1.1 and immune-related (ir)RECIST.

      III. To determine overall survival (OS) on COTEZO in cohorts of advanced rare tumors.

      IV. To determine disease control rate (DCR) and duration of response (DOR) on COTEZO in
      cohorts of advanced rare tumors per RECIST v1.1 and irRECIST.

      V. To determine safety profile and adverse events encountered by patients with advanced rare
      tumors treated with COTEZO.

      TRANSLATIONAL OBJECTIVES:

      I. To collect and bank tumor tissue and peripheral blood for future correlative analyses from
      patients with advanced rare tumors treated with COTEZO.

      OUTLINE:

      Participants receive cobimetinib orally (PO) once daily (QD) on days 1-21 and atezolizumab
      intravenously (IV) over 60 minutes on days 1 and 15. Courses repeat every 28 days in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, participants followed up every 3 months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cobimetinib, atezolizumab)ExperimentalParticipants receive cobimetinib PO QD on days 1-21 and atezolizumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Atezolizumab
  • Cobimetinib

Eligibility Criteria

        Inclusion Criteria:

          -  Must have histologically or cytologically documented rare tumor as defined per
             protocol that is metastatic or locally advanced and unresectable. Patients with
             locally advanced cutaneous squamous cell carcinoma that are technically resectable but
             in whom surgery is expected to lead to substantial function impairment or
             disfigurement are eligible

          -  Must be refractory or intolerant to standard lines of therapy

          -  Presence of radiographically evaluable disease

          -  Must have completed prior chemotherapy, immunotherapy, or radiation therapy at least
             14 days prior to start of treatment and all toxicity must be resolved to Common
             Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 1 (with the exception of
             CTCAE v4.0 grade 2 neuropathy) prior to start of treatment

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Tissue Parameters: a. Representative formalin-fixed paraffin-embedded (FFPE) tumor
             specimens in paraffin blocks (blocks are preferred) or at least 4 unstained slides,
             with an associated pathology report, for testing of tumor PD-L1 expression (tumor
             tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not
             acceptable). b. Tumor tissue should be of good quality based on total and viable tumor
             content. Fine needle aspiration, brushing, cell pellet from pleural effusion, bone
             metastases, and lavage samples are not acceptable. For core-needle biopsy specimens,
             at least three cores should be submitted for evaluation. c. Patients who do not have
             tissue specimens meeting eligibility requirements must be willing to undergo a biopsy
             during the screening period

          -  Absolute neutrophil count (ANC) >= 1,000/mcL (obtained within 14 days prior to
             enrollment)

          -  Platelets >= 75,000/mcL (obtained within 14 days prior to enrollment)

          -  Hemoglobin >= 9 g/dL (obtained within 14 days prior to enrollment)

          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
             phosphatase (ALP) =< 3 x institutional upper limit of normal (IULN) without liver mets
             or =< 5 x IULN with liver metastases (obtained within 14 days prior to enrollment)

          -  Bilirubin =< 1.5 mg/dL (obtained within 14 days prior to enrollment)

          -  Calculated creatinine clearance > 30 ml/min (obtained within 14 days prior to
             enrollment)

          -  Patients must be informed of investigational nature of this study and must be willing
             to give written informed consent in accordance with institutional and federal
             guidelines. Patients must be able to comply with the requirements and assessments of
             the study protocol

          -  Fertile men and women must use an effective method of contraception during treatment
             and for at least 6 months after completion of treatment as directed by their
             physician. Effective methods of contraception are defined as those that result in a
             low failure rate (i.e., less than 1% per year) when used consistently and correctly
             (e.g., implants, injectables, combined oral contraception or intra-uterine devices).
             At the discretion of the Investigator, acceptable methods of contraception may include
             total abstinence in cases where the lifestyle of the patient ensures compliance.
             (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation
             methods] and withdrawal are not acceptable methods of contraception)

        Exclusion Criteria:

          -  For individual baskets: Appendiceal adenocarcinoma: Must not have clinically
             symptomatic malignant bowel obstruction; Cutaneous squamous cell carcinoma: none;
             Small bowel adenocarcinoma: must not have clinically symptomatic malignant small bowel
             obstruction

          -  Presence of brain metastases (unless they have been adequately treated with
             radiotherapy or surgery and stable for at least 30 days prior to enrollment provided
             patient is neurologically asymptomatic and without corticosteroid treatment for at
             least 7 days prior to enrollment)

          -  Uncontrolled intercurrent illness including, but not limited to diabetes,
             hypertension, severe infection, severe malnutrition, unstable angina, class III-IV New
             York Heart Association (NYHA) congestive heart failure, ventricular arrhythmias,
             active ischemic heart disease, or myocardial infarction within 6 months prior to
             enrollment

          -  History of or evidence of retinal pathology on ophthalmologic examination that is
             considered a risk factor for neurosensory retinal detachment, central serous
             chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration

          -  Patients will be excluded from study participation if they currently are known to have
             any of the following risk factors for RVO: a. Glaucoma with intraocular pressure >= 21
             mmHg b. Grade >= 2 serum cholesterol c. Grade >= 2 hypertriglyceridemia d. Grade >= 2
             or symptomatic hyperglycemia (fasting) e. Grade >= 2 uncontrolled hypertension
             (patients with a history of hypertension controlled with anti-hypertensive medication
             to grade =< 1 are eligible

          -  Active malignancy (other than colorectal carcinoma [CRC]) or a history of prior
             malignancy within the past 3 years. Adequately treated basal cell or squamous cell
             skin cancer, in situ cervical cancer, ductal carcinoma in situ, other low grade
             lesions such as incidental appendix carcinoid, or any other cancer from which the
             patient has been disease and treatment free for two years are allowed. Prostate cancer
             patients on active surveillance are eligible

          -  Pregnant or nursing patients due to risk of fetal or nursing infant harm. Women/men of
             reproductive potential who do not agree to use an effective contraceptive method while
             on study and for at least 6 months after study treatment

          -  Exclusion criteria related to study medication (any cancer immunotherapy including
             CD137 agonists, anti-PD-1, anti-PD-L1, or anti-CTLA4 or any MEK or ERK inhibitor)

          -  Left ventricular ejection fraction (LVEF) < institutional lower limit of normal or <
             50%

          -  History or risk of autoimmune disease, including but not limited to systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's
             syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune
             thyroid disease, vasculitis, or glomerulonephritis a. Patients with a history of
             autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be
             eligible. b. Patients with controlled type 1 diabetes mellitus on a stable insulin
             regimen may be eligible. c. Patients with eczema, psoriasis, lichen simplex chronicus
             of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic
             arthritis would be excluded) are permitted provided that they meet the following
             conditions:

               -  Patients with psoriasis must have a baseline ophthalmologic exam to rule out
                  ocular manifestations

               -  Rash must cover less than 10% of body surface area (BSA)

               -  Disease is well controlled at baseline and only requiring low potency topical
                  steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone
                  0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)

               -  No acute exacerbations of underlying condition within the last 12 months (not
                  requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids,
                  biologic agents, oral calcineurin inhibitors; high potency or oral steroids)

          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
             tomography (CT) scan a. History of radiation pneumonitis in the radiation field
             (fibrosis) is permitted

          -  History of human immunodeficiency virus (HIV) infection or active hepatitis B (chronic
             or acute) or hepatitis C infection. a. Patients with past or resolved hepatitis B
             infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a
             positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
             b. Patients positive for hepatitis C virus (HCV) antibody are eligible only if
             polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)

          -  Active tuberculosis or severe infections within 4 weeks prior to cycle 1, day 1,
             including but not limited to hospitalization for complications of infection,
             bacteremia, or severe pneumonia

          -  Treatment with systemic immuno-stimulatory agents (including but not limited to
             interferon [IFN] or interleukin [IL]-2) within 6 weeks or five half-lives of the drug
             (whichever is shorter) prior to cycle 1, day 1

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

          -  Prior allogeneic bone marrow transplantation or prior solid organ transplantation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:8 weeks
Safety Issue:
Description:ORR (partial response (PR) or complete response (CR) measured as per RECIST 1.1.

Secondary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:2 weeks after last dose of study drugs
Safety Issue:
Description:PFS assessed per RECIST v1.1.
Measure:Progression-Free Survival (PFS)
Time Frame:2 weeks after last dose of study drugs
Safety Issue:
Description:PFS assessed per irRECIST.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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