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BRIEF 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

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


  • Org Study ID: ML28897
  • Secondary ID: PRO 02
  • NCT ID: NCT02091141
  • NCT Alias:
  • Sponsor: Genentech, Inc. - Industry
  • Source: Genentech, Inc.

Brief Summary

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.

Overal Status Start Date Phase Study Type
Recruiting April 14, 2014 Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator

Primary Outcome 1 - 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)

Primary Outcome 2 - Measure: Percentage of Atezolizumab-Treated Participants With Tissue Tumor Mutational Burden (tTMB) ≥16 Mutations/Mb With Overall Response, as Assessed by the Independent Review Committee (IRC)

Primary Outcome 2 - 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)

Condition:

  • Neoplasms
  • Solid Tumors
  • Biliary Cancer
  • Salivary Cancer
  • Bladder Cancer

Eligibility

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 disease by RECIST v1.1

- Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 (For
patients enrolling in the atezolizumab arm, ECOG score must be documented within 7
days prior to first treatment and confirmation of ECOG PS must be entered into the
interactive web response system [IWRS] prior to initiation of treatment)

- Adequate hematologic, renal, and liver function as defined by the protocol

- 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 or amplification. Participants must have one of the following tumor
types: biliary cancer, salivary cancer, or bladder cancer

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

- 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 pre-treatment tissue sample is required if
molecular testing was not performed by Foundation Medicine. Any available tumor tissue
sample can be submitted. The tissue sample must be submitted within 4 weeks after
enrollment

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 enrollment)

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 enrollment)

Atezolizumab

- Molecular testing results from CLIA-certified laboratories (using tissue)
demonstrating elevated tissue tumor mutational burden (tTMB ≥10 mutations/ Megabase
[Mb])

- For patients where molecular testing was not performed using Foundation Medicine,
submission of an archival or new pretreatment tissue sample is mandatory. For patients
where molecular testing was performed using Foundation Medicine, submission of an
archival or new pretreatment tissue sample is required, if available. The tissue
sample must 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; Radiation 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

Study-Drug Specific Exclusion Criteria:

Trastuzumab plus Pertuzumab

- 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
- 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

- History of leptomeningeal disease

- Uncontrolled tumor pain

- Asymptomatic metastatic lesions that would likely cause functional deficits or
intractable pain with further growth (e.g., epidural metastasis that is not currently
associated with spinal cord compression) should be considered for loco-regional
therapy if appropriate prior to enrollment

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently). Patients with indwelling
catheters are allowed

- Uncontrolled or symptomatic hypercalcemia

- 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
or within 5 months after the final dose of atezolizumab

- 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
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Clinical Trials

Role: Study Director

Affiliation: Hoffmann-La Roche

Overall Contact

Name: Reference Study ID Number: ML28897 www.roche.com/about_roche/roche_worldwide.htm

Phone: 888-662-6728 (U.S. and Canada)

Email: global-roche-genentech-trials@gene.com

Locations

Facility Status Contact
Western Regional Medical Center at Cancer Treatment Centers of America
Goodyear, Arizona 85338
United States
Recruiting
Mayo Clinic Arizona
Phoenix, Arizona 85259
United States
Recruiting
Highlands Oncology Group
Rogers, Arkansas 72758
United States
Recruiting
Science 37, Inc
Culver City, California 90230
United States
Completed
City of Hope Comprehensive Cancer Center
Duarte, California 91010
United States
Recruiting
Moores UCSD Cancer Center; Dept Clinical Trials Office
La Jolla, California 92093-0698
United States
Recruiting
Stanford Comprehensive Cancer Center
Stanford, California 94305
United States
Recruiting
University of Colorado
Aurora, Colorado 80045-2517
United States
Recruiting
Yale Cancer Center
New Haven, Connecticut 06520
United States
Terminated
SCRI Florida Cancer Specialists South
Fort Myers, Florida 33916
United States
Recruiting
Mayo Clinic
Jacksonville, Florida 32224
United States
Recruiting
Florida Hospital Cancer Inst; Memorial System Onc Clin Rsch
Orlando, Florida 32804
United States
Recruiting
Florida Cancer Specialist, North Region
Saint Petersburg, Florida 33705
United States
Recruiting
Florida Cancer Specialists, Research Department
West Palm Beach, Florida 33401
United States
Recruiting
University Cancer & Blood Center, LLC; Research
Athens, Georgia 30607
United States
Recruiting
Northeast Georgia Medical Center; Oncology Research Dept-5C
Gainesville, Georgia 30501
United States
Recruiting
Southeastern Regional Medical Center, Inc.
Newnan, Georgia 30265
United States
Recruiting
Northwestern University; Robert H. Lurie Comp Can Ctr; Northwestern Medicine Development Inst
Chicago, Illinois 60611
United States
Recruiting
University Of Chicago Medical Center; Section Of Hematology/Oncology
Chicago, Illinois 60637
United States
Recruiting
Midwestern Regional Med Center
Zion, Illinois 60099
United States
Recruiting
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland 21287
United States
Recruiting
Mayo Foundation
Rochester, Minnesota 55905
United States
Recruiting
Research Medical Center - Antibiotic Research Associates, Inc.
Kansas City, Missouri 64132
United States
Recruiting
Weill Cornell Univ Medical Ctr; Breast Cancer Center
New York, New York 10021
United States
Recruiting
Herbert Irving Comprehensive Cancer Center; Herbert Irving Pavillion
New York, New York 10032
United States
Recruiting
Univ No Carolina School of Med; Physicians Office Bldg
Chapel Hill, North Carolina 27599-7305v
United States
Recruiting
Duke University Medical Center
Durham, North Carolina 27710
United States
Recruiting
Wake Forest Univ Health Svcs; Internal Medicine
Winston-Salem, North Carolina 27157
United States
Recruiting
Sanford Roger Maris Cancer Center
Fargo, North Dakota 58102
United States
Recruiting
Oncology Hematology Care Inc
Cincinnati, Ohio 45242
United States
Recruiting
Cleveland Clinic
Cleveland, Ohio 44106
United States
Recruiting
University Hospitals of Cleveland
Cleveland, Ohio 44106
United States
Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Recruiting
Southwestern Reg Med Ctr Inc
Tulsa, Oklahoma 74133
United States
Terminated
Providence Portland Medical Center
Portland, Oregon 97213
United States
Recruiting
Abington Mem Hosp-Abington; Rose. Can Ctr,Gyn Onc Ins
Abington, Pennsylvania 19001
United States
Recruiting
Abramson Cancer Center
Philadelphia, Pennsylvania 19104
United States
Completed
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107
United States
Recruiting
Eastern Regional Medical Ctr
Philadelphia, Pennsylvania 19124
United States
Recruiting
UPMC - Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
United States
Recruiting
Sanford Cancer Cnt Onco Clinic
Sioux Falls, South Dakota 57104
United States
Recruiting
SCRI Tennessee Oncology Chattanooga
Chattanooga, Tennessee 37404
United States
Recruiting
West Clinic
Germantown, Tennessee 38138
United States
Recruiting
Tennessee Onc., PLLC - SCRI
Nashville, Tennessee 37203
United States
Recruiting
Vanderbilt Ingram Cancer Clinic
Nashville, Tennessee 37232
United States
Recruiting
The Center for Cancer and Blood Disorders - Fort Worth
Fort Worth, Texas 76104
United States
Terminated
MD Anderson
Houston, Texas 77030
United States
Recruiting
Virginia Cancer Institute
Richmond, Virginia 23226
United States
Recruiting
Northwest Medical Specialties
Tacoma, Washington 98405
United States
Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United States
Recruiting