With the increased availability of next-generation sequencing, oncologists are starting to incorporate genomic profiling into routine care of cancer patients. If a genomic alteration is identified during profiling, it could help guide the choice of therapy and improve treatment outcomes. This study will examine the anti-tumor activity of two FDA-approved therapies to treat patients who were previously profiled with next-generation sequencing technology and who failed first-line treatment for one of the following tumor types: non-small cell lung cancers; urothelial cancer; non-colon gastrointestinal cancers, and upper aerodigestive tract cancer.
This pilot study will evaluate preliminary antitumor activity of two FDA-approved targeted
therapies, regorafenib (Stivarga, Bayer) and afatinib (Gilotrif, Boehringer Ingelheim) in
patients who have either failed first-line treatment, or for which no standard treatment is
available, for one of the following four tumor types:
1. non-small cell lung cancer,
2. urothelial carcinoma,
3. non-colon gastrointestinal cancers, and
4. upper aerodigestive tract cancers (lip, tongue, salivary glands, gum, mouth, oral
cavity, tonsils, oropharynx, nasopharynx, nasal cavity, sinus, and larynx tumors).
Approximately 160 patients (40 per tumour type) are planned for enrollment. Consideration for
enrollment will be based on results from profiling with next-generation sequencing technology
that was performed outside of the protocol. Eligible patients will receive one of the
FDA-approved targeted agents at the recommended dose. The treating physician will decide
which targeted agent to prescribe based on the genomic alterations per tumor type and the
targets listed in the package insert for each agent.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||September 28, 2016||Phase 2||Interventional|
Primary Outcome 1 - Measure: Overall response rate (ORR)
Primary Outcome 1 - Time Frame: every 8 weeks until tumor progression or treatment discontinuation, an expected average of 1 year.
- Patients with a histologically or cytologically confirmed diagnosis of one of the
following tumor types whose disease has progressed following one line of standard
therapy and/or for which no standard treatment is available that has been shown to
1. Non-small cell lung cancer
2. Urothelial carcinoma
3. Non-colon gastrointestinal cancers (including hepatobiliary, pancreatic, and
4. Upper aerodigestive tract cancers (including lip, tongue, salivary gland, gum,
oral cavity, mouth, tonsils, oropharynx, nasopharynx, nasal cavity, sinus, and
- Patients must have a predefined genomic alteration that can be targeted with either
afatinib or regorafenib
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Adequate hematologic, hepatic and liver function.
- Patients who are therapeutically treated with an agent such as warfarin or heparin are
allowed provided their dose and INR/PTT are stable. Close monitoring is mandatory.
- Must comply with instructions to prevent contraception.
- Must be willing and able to comply with study and follow-up procedures.
- Must be able to understand the nature of the study and give written informed consent.
- Two or more prior chemotherapy regimens in the metastatic setting.
- Most recent chemotherapy ≤ 3 weeks and > Grade 1 chemotherapy-related side effects,
with the exception of neuropathy (> grade 2 excluded) and alopecia.
- Use of a study drug or targeted therapy ≤21 days or 5 half-lives (whichever is
shorter) prior to the first dose of study treatment. For study drugs for which 5
half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and
administration of study treatment is required.
- Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89)
administered ≤28 days or limited field radiation for palliation ≤7 days prior to
starting study drug or has not recovered from side effects of such therapy.
- Major surgical procedures ≤28 days of beginning study drug, or minor surgical
procedures ≤7 days. No waiting required following port-a-cath placement.
- Previously untreated brain metastases. Patients who have received radiation or surgery
for brain metastases are eligible if therapy was completed at least 2 weeks prior to
study entry and there is no evidence of central nervous system disease progression,
mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.
Enzyme-inducing anti-convulsants are contraindicated.
- Pregnant or lactating
- Acute or chronic liver, renal, or pancreas disease.
- Presence of active gastrointestinal disease or other condition that will interfere
significantly with the absorption, distribution, metabolism, or excretion of oral
therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2,
and malabsorption syndrome).
- Any of the following cardiac diseases currently or within the last 6 months:
- Unstable angina pectoris
- Congestive heart failure (New York Heart Association (NYHA) ≥ Grade 2)
- Acute myocardial infarction
- Conduction abnormality not controlled with pacemaker or medication
- Significant ventricular or supraventricular arrhythmias (patients with chronic
rate-controlled atrial fibrillation in the absence of other cardiac abnormalities
- Valvular disease with significant compromise in cardiac function
- Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >180 mmHg or
diastolic blood pressure (DBP) >100 mmHg) (patients with values above these levels
must have their blood pressure (BP) controlled with medication prior to starting
- Thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident
(including transient ischemic attacks) deep vein thrombosis or pulmonary embolism
within 6 months of start of treatment.
- Evidence or history of bleeding diathesis or coagulopathy; any haemorrhage or bleeding
event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of treatment.
- Presence of a non-healing wound, non-healing ulcer, or bone fracture.
- Patients with phaeochromocytoma.
- Serious active infection at the time of treatment, or another serious underlying
medical condition that would impair the ability of the patient to receive protocol
- Known diagnosis of human immunodeficiency virus, hepatitis B or C.
- Presence of other active cancers unless indolent and not requiring therapy. Patients
with Stage I cancer who have received definitive local treatment and are considered
unlikely to recur are eligible. All patients with previously treated in situ carcinoma
(i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin
- Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Howard A. Burris, III, MD
Role: Study Chair
Affiliation: SCRI Development Innovations, LLC
Name: SCRI Development Innovations, LLC
|Sarah Cannon Research Institute at HealthOne
Denver, Colorado 80218
|Florida Cancer Specialists - South
Fort Myers, Florida 33916
|Florida Cancer Specialists - North
Saint Petersburg, Florida 33705
|Florida Cancer Specialists - East
West Palm Beach, Florida 33401
|Research Medical Center - HCA Midwest
Kansas City, Missouri 64132
Chattanooga, Tennessee 37404
Nashville, Tennessee 37203