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My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT02091141
First received: March 17, 2014
Last updated: June 1, 2017
Last verified: June 2017
  Purpose
This multicenter, non-randomized, open-label study will evaluate the efficacy and safety of six treatment regimens in participants with advanced solid tumors for whom therapies that will convey clinical benefit are not available and/or are not suitable options per the treating physician's judgment.

Condition Intervention Phase
Neoplasms Drug: Trastuzumab Drug: Pertuzumab Drug: Erlotinib Drug: Vemurafenib Drug: Cobimetinib Drug: Vismodegib Drug: Alectinib Drug: Atezolizumab Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: My Pathway: An Open-Label Phase IIa Study Evaluating Trastuzumab/Pertuzumab, Erlotinib, Vemurafenib/Cobimetinib, Vismodegib, Alectinib, and Atezolizumab in Patients Who Have Advanced Solid Tumors With Mutations or Gene Expression Abnormalities Predictive of Response to One of These Agents

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Percentage of Participants With Overall Response [ Time Frame: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years) ]
    Tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) for all arms except atezolizumab; immune-modified RECIST (imRECIST) will be used for atezolizumab arm.


Secondary Outcome Measures:
  • Percentage of Participants With Disease Control [ Time Frame: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years) ]
    Tumor response will be assessed using RECIST for all arms except atezolizumab; imRECIST will be used for atezolizumab arm.

  • Progression-Free Survival (PFS) [ Time Frame: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years) ]
    Tumor response will be assessed using RECIST for all arms except atezolizumab; imRECIST will be used for atezolizumab arm.

  • Percentage of Participants who are Alive at Year 1 [ Time Frame: 1 year ]
  • Duration of Response [ Time Frame: From the date of first documented response (complete response [CR] or partial response [PR]) to the time of disease progression or death from any cause, whichever occurs first (up to approximately 5 years) ]
    Tumor response will be assessed using RECIST for all arms except atezolizumab; imRECIST will be used for atezolizumab arm.

  • Percentage of Participants With Overall Response as Determined by Independent Review Committee (IRC) in Colorectal Cancer Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Amplification or Overexpression With a Tumor Response of CR or PR [ Time Frame: From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years) ]
    Tumor response will be assessed using RECIST for all arms except atezolizumab; imRECIST will be used for atezolizumab arm.

  • Percentage of Participants With Adverse Events [ Time Frame: From first study treatment administration to 30 days (45 days for vismodegib, 90 days for atezolizumab) after the last dose (up to approximately 5 years) ]

Estimated Enrollment: 500
Actual Study Start Date: April 14, 2014
Estimated Study Completion Date: August 31, 2019
Estimated Primary Completion Date: August 31, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trastuzumab Plus Pertuzumab
Participants will receive trastuzumab 8 milligrams per kilogram (mg/kg) intravenous (IV) infusion as loading dose, followed by 6 mg/kg IV infusion every 3 weeks; and pertuzumab 840 mg IV infusion as loading dose, followed by 420 mg IV infusion every 3 weeks.
Drug: Trastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
Other Name: Herceptin
Drug: Pertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
Other Name: Perjeta
Experimental: Erlotinib
Participants will receive erlotinib 150 milligrams (mg) orally once daily in each 28-day cycle.
Drug: Erlotinib
Erlotinib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
Other Name: Tarceva
Experimental: Vemurafenib Plus Cobimetinib
Participants will receive vemurafenib 960 mg orally twice daily (BID) in each 28-day cycle; and cobimetinib 60 mg orally once daily for 21 days on and 7 days off in each 28-day cycle.
Drug: Vemurafenib
Vemurafenib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
Other Name: Zelboraf
Drug: Cobimetinib
Cobimetinib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
Other Name: Cotellic
Experimental: Vismodegib
Participants will receive vismodegib 150 mg orally once daily in each 28-day cycle.
Drug: Vismodegib
Vismodegib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
Other Name: Erivedge
Experimental: Alectinib
Participants will receive alectinib 600 mg orally BID in each 28-day cycle.
Drug: Alectinib
Alectinib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
Other Name: Alecensa
Experimental: Atezolizumab
Participants will receive atezolizumab 1200 mg IV infusion every 3 weeks.
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.
Other Name: Tecentriq

  Eligibility

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

General Inclusion Criteria:

  • Life expectancy greater than or equal to (>/=) 12 weeks
  • Histologically documented metastatic cancer (solid tumors, not including hematologic malignancies)
  • Participants who have received standard first-line therapy for metastatic cancer (except for the tumors for which no first-line therapy exists) and in whom a trial of targeted therapy is considered the best available treatment option. Eligible participants should not have available therapies that will convey clinical benefit and/or are not suitable options per the treating physician's judgment
  • No previous treatment with the specific assigned study drug or any other drug sharing the same target
  • Measurable or evaluable disease by RECIST v1.1
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0, 1, or 2
  • Adequate hematologic, renal, and liver function
  • If applicable, use of contraception methods or abstinence as defined by the protocol

Study-Drug Specific Inclusion Criteria:

Trastuzumab plus Pertuzumab

  • Molecular testing results from clinical laboratory improvement amendments (CLIA)-certified laboratories (using tissue and/or blood) demonstrating HER2 overexpression, amplification, or HER2-activating mutation

    a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrollment)

  • Participants with breast, gastric, or gastroesophageal junction cancer must have HER2-activating mutation
  • Left ventricular ejection fraction (LVEF) greater than (>) 50 percent (%) or above the lower limit of the institutional normal range, whichever is lower
  • Availability of an archival or new pretreatment tissue sample is required if molecular testing was not performed by Foundation Medicine. Any available tumor tissue sample can be submitted. The tissue sample may be submitted within 4 weeks after enrolment

Erlotinib

  • Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating EGFR-activating mutations

Vemurafenib plus Cobimetinib

  • Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating BRAF V600 mutations a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrolment)

Vismodegib

  • Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating hedgehog pathway relevant mutation (activating mutation of smoothened [SMO] or loss-of-function mutation of protein patched homolog-1 [PTCH-1])

    a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrollment)

  • All non-hematological adverse events related to any prior chemotherapy, surgery, or radiotherapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade less than or equal to (</=) 2 prior to starting therapy

Alectinib

  • Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating anaplastic lymphoma kinase (ALK) gene rearrangements, ALK mutations, ALK copy number gain or (for melanoma only) increased ALK expression or presence of ALK-alternative transcription initiation transcript (ALKATI) a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrolment)

Atezolizumab

  • Molecular testing results from CLIA-certified laboratories (using tissue) demonstrating programmed death-ligand 1 (PD-L1) copy number gain/amplification, deficiency in mismatch repair enzymes (dMMR), high levels of microsatellite instability (MSI-H), high tumor mutational burden (TMB-H), alterations of deoxyribonucleic acid (DNA) proofreading/repair genes (example., polymerase epsilon [POLE], polymerase delta 1 [POLD1])
  • Availability of an archival or new pretreatment tissue sample is required if molecular testing was not performed by Foundation Medicine. Any available tumor tissue sample can be submitted. The tissue sample may be submitted within 4 weeks after enrollment

General Exclusion Criteria:

  • Participants with hematologic malignancies
  • Concurrent administration of any other anti-cancer therapy (except male participants with prostate cancer receiving androgen blockade: Bisphosphonates and denosumab are allowed; Most recent anti-cancer therapy </=28 days and have not recovered from the side effects, excluding alopecia; Radiaiton therapy within </=14 days
  • Active or untreated brain metastases
  • History of carcinomatous meningitis
  • Uncontrolled concurrent malignancy (early stage is allowed if not requiring active therapy or intervention)
  • Pregnant or breastfeeding women, or intending to become pregnant during the study
  • Any significant cardiovascular events within 6 months prior to study entry
  • Pulmonary embolism within 30 days prior to study entry
  • History or presence of clinically significant ventricular or atrial dysrhythmia >Grade 2 per NCI CTCAE v4.0
  • Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
  • Eligible for another actively accruing Roche/Genentech-sponsored interventional clinical trial

Study-Drug Specific Exclusion Criteria:

Trastuzumab plus Pertuzumab

  • Breast, gastric, or gastroesophageal junction cancer identified by HER2 amplification or overexpression
  • Previous treatment with any HER2-targeted therapy

Erlotinib

  • Non-small cell lung cancer (NSCLC) or pancreatic cancer identified by exon 19 deletions or exon 21 L858R substitution mutations
  • EGFR amplifications in the absence of EGFR-activating mutations
  • Cancers with exon 20 mutations
  • Previous treatment with erlotinib or any other EGFR inhibitor
  • Inability to swallow pills
  • Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude absorption of erlotinib

Vemurafenib plus Cobimetinib

  • Malignant melanoma, papillary thyroid cancer, colorectal cancer, or hematologic malignancy including multiple myeloma
  • LVEF below institutional lower level of normal (LLN) or below 50%, whichever is lower
  • History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration
  • Presence of any of the following conditions, which are risk factors for RVO: Uncontrolled glaucoma with intraocular pressure >21 millimetres of mercury (mm Hg); Serum cholesterol >/=Grade 2; Hypertriglyceridemia >/=Grade 2; Hyperglycemia (fasting) >/=Grade 2; Grade >/=2 uncontrolled hypertension (participants with a history of hypertension controlled with anti-hypertensive medication to Grade </=1 are eligible)
  • Prior or concurrent malignancy with known RAS mutation
  • Previous treatment with vemurafenib or any other BRAF inhibitor (prior sorafenib is allowed)
  • Previous treatment with cobimetinib or any other mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor
  • Prior treatment with a RAF inhibitor
  • Inability to swallow pills
  • Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude absorption of vemurafenib
  • History of congenital long QT syndrome or mean (average of triplicate measurements) corrected QT (QTc) measured using Fridericia's method >/=450 millisecond (ms) at baseline or uncorrectable abnormalities in serum electrolytes (sodium, potassium, calcium, magnesium, phosphorus)

Vismodegib

  • Basal cell carcinoma of the skin, medulloblastoma, small-cell lung cancer, or hematologic malignancies
  • Previous treatment with vismodegib or any other hedgehog pathway inhibitor
  • Inability to swallow pills
  • Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude absorption of vismodegib

Alectinib

  • ALK-positive NSCLC, neuroblastoma, and childhood tumors
  • Previous treatment with alectinib or any other ALK inhibitor
  • Participants with symptomatic bradycardia
  • Administration of strong/potent cytochrome P3A4 (CYP3A4) inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment with alectinib
  • Inability to swallow pills
  • Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude absorption of alectinib

Atezolizumab

  • Metastatic NSCLC, metastatic urothelial carcinoma or microsatellite instability high metastatic colorectal cancer
  • Previous treatment with atezolizumab or another programmed death-1 (PD-1)/PD-L1 inhibitor
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells
  • Known allergy or hypersensitivity to any component of the atezolizumab formulation
  • Active or history of autoimmune disease or immune deficiency
  • Prior allogeneic stem cell or solid organ transplantation
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Positive human immunodeficiency virus (HIV) test, active hepatitis B virus (HBV) infection, active hepatitis C virus (HCV) infection or active tuberculosis
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the course of the study
  • History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk from treatment complications
  • Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies
  • Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug (whichever is longer) prior to randomization
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
  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: NCT02091141

Contacts
Contact: Reference Study ID Number: ML28897 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

  Show 44 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02091141     History of Changes
Other Study ID Numbers: ML28897
PRO 02 ( Other Identifier: Genentech, Inc. )
Study First Received: March 17, 2014
Last Updated: June 1, 2017

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

Additional relevant MeSH terms:
Pertuzumab
Trastuzumab
Erlotinib Hydrochloride
Antibodies, Monoclonal
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 28, 2017