Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, and Erivedge Treatment Targeted Against Certain Mutations in Cancer Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT02091141
First received: March 17, 2014
Last updated: September 1, 2016
Last verified: September 2016
  Purpose
This is a multicenter, non-randomized, open-label study designed to evaluate four treatment regimens in patients with advanced cancer for whom there is no available, beneficial treatment. Patients with HER2 overexpression, amplification, or -activating mutation will be treated with Herceptin/Perjeta; those with epidermal growth factor receptor (EGFR), with Tarceva; those with BRAF-activating mutation, with Zelboraf/Cotellic; and those with Hedehog pathway potentially clinically relevant mutation, with Erivedge. Treatment will continue until disease progression or unacceptable toxicity occurs. Study is expected to last up to 5 years.

Condition Intervention Phase
Neoplasms
Drug: Cobimetinib [Cotellic]
Drug: Erlotinib [Tarceva]
Drug: Pertuzumab [Perjeta]
Drug: Trastuzumab [Herceptin]
Drug: Vemurafenib [Zelboraf]
Drug: Vismodegib [Erivedge]
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: My Pathway: An Open Label Phase IIa Study Evaluating Trastuzumab/Pertuzumab, Erlotinib, Vemurafenib/Cobimetinib, and Vismodegib 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:
  • Overall response rate as determined by the investigator according to response evaluation in solid tumors (RECIST) v. 1.1 criteria [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease control rate, defined as the proportion of patients whose best response is complete response, partial response or stable disease [ Time Frame: Approximately 1 year ] [ Designated as safety issue: No ]
  • Progression-free survival, defined as the time from first study treatment to until disease progression as assessed by the investigator, or death from any cause [ Time Frame: Approximately 1 year ] [ Designated as safety issue: No ]
  • Overall survival, defined as the survival rate 1 year from the date of first treatment [ Time Frame: Approximately 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 500
Study Start Date: April 2014
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erivedge (vismodegib) Drug: Vismodegib [Erivedge]
A daily dose of 150 mg given orally in cycles of 28 days (4 weeks) duration
Experimental: Herceptin/Perjeta (trastuzumab/pertuzumab) Drug: Pertuzumab [Perjeta]
An 840 mg IV loading dose, followed by 420 mg, given by IV every 3 weeks
Drug: Trastuzumab [Herceptin]
An 8 mg/kg intravenous (IV) loading dose, followed by 6 mg/kg, given by IV infusion every 3 weeks
Experimental: Tarceva (erlotinib) Drug: Erlotinib [Tarceva]
A daily dose of 150 mg given orally in cycles of 28 days (4 weeks) duration
Experimental: Zelboraf/Cotellic (vemurafenib/cobimetinib) Drug: Cobimetinib [Cotellic]
A daily dose of 60 mg given orally for 21 days on and 7 days off in cycles of 28 days (4 weeks) duration
Drug: Vemurafenib [Zelboraf]
960 mg given twice-daily (BID) orally in cycles of 28 days (4 weeks) duration

  Eligibility

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

Inclusion Criteria:

  • Age >/= 18 years
  • Life expectancy >/= 12 weeks
  • Histologically documented metastatic cancer (solid tumors, not including hematologic malignancies)
  • Molecular testing results from certified laboratories (using tissue from the most recent tumor biopsy in the metastatic setting) that show at least one of the following abnormalities:
  • HER2 overexpression, amplification, or HER2-activating mutation
  • EGFR-activating mutation
  • BRAF-activating mutation
  • Hedgehog pathway potentially clinically relevant mutation (activating mutation of SMO or loss-of-function mutation of PTCH-1)
  • Patients 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 patients should not have available therapies that will convey clinical benefit.
  • No previous treatment with the specific assigned study drug or any other drug sharing the same target
  • Progressive cancer at the time of study entry
  • Measurable or evaluable disease by RECIST v. 1.1
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0, 1, or 2
  • Adequate hematologic, renal, and liver function
  • Use of effective contraception as defined by the protocol

Study-drug specific criteria:

  • Trastuzumab plus Pertuzumab
  • Patients with solid tumors that have HER2 overexpression, amplification, or HER2-activating mutation
  • Patients with breast, gastric, or gastroesophageal junction cancer must have HER2-activating mutation.
  • Left ventricular ejection fraction (LVEF) > 50% or above the lower limit of the institutional normal range, whichever is lower
  • Erlotinib
  • Patients with solid tumors that harbor EGFR-activating mutations
  • Vemurafenib
  • BRAF mutation positivity as determined by next generation sequencing (NGS) or real time-polymerase chain reaction (RT-PCR) will be accepted.
  • Vismodegib
  • Hedgehog-activating mutation positivity
  • 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 </= 2 prior to starting therapy.

Exclusion Criteria:

  • Patients with hematologic malignancies
  • Concurrent administration of any other anti-cancer therapy (except male patients 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)
  • Women who are breastfeeding or pregnant
  • 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 (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [NCI CTCAE v4.0])
  • Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality
  • Eligible for another actively accruing Roche/Genentech-sponsored interventional clinical trial

Study-drug specific 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 and exon 21 mutations
  • Cancers with exon 20 mutations
  • Previous treatment with erlotinib or any other EGFR inhibitor
  • Vemurafenib plus Cobimetinib
  • Malignant melanoma, papillary thyroid cancer, colorectal cancer, or hematologic malignancy including multiple myeloma
  • Left ventricular ejection fraction (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 condition, which are risk factors for RVO: Uncontrolled glaucoma with intraocular pressure >21 mm Hg, Serum cholesterol >/= Grade 2, Hypertriglyceridemia >/= Grade 2, and Hyperglycemia (fasting) >/= Grade 2
  • 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 RAF inhibitor
  • Prior treatment with a MEK inhibitor
  • Corrected QT (QTc) interval ≥450 msec at baseline or history of congenital long QT syndrome
  • 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
  • Breast cancer patients taking hormone replacement therapy or hormonal birth control
  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.rochegenentechtrials@roche.com

  Show 42 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 
Study First Received: March 17, 2014
Last Updated: September 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pertuzumab
Erlotinib Hydrochloride
Trastuzumab
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2016