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 selected commercially available molecularly matched targeted therapies in patients who have 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 four-arm pilot phase II study will evaluate the preliminary antitumor activity of
selected commercially available molecularly matched targeted therapies in patients who have
failed first line treatment for one of the following 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.
1. 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
2. Patients must have a predefined genomic alteration that can be targeted with any of
the FDA-approved targeted agents used in this study.
3. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
5. Age greater than or equal to 18 years.
6. Adequate hematologic function defined as:
- Absolute neutrophil count (ANC) ≥1500/μL
- Platelets ≥75,000/μL
7. Adequate liver function defined as:
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x the
upper limit of normal (ULN) or ≤ 5.0 X ULN if liver metastases present
- Total bilirubin ≤1.5 x ULN (unless the patient has Grade 1 bilirubin elevation
due to Gilbert's disease or a similar syndrome involving slow conjugation of
8. Adequate renal function defined as serum creatinine ≤1.5 x the upper limit of normal
OR measured or calculated creatinine clearance ≥50 mL/min for patients with creatinine
levels greater than or equal to 1.5 x the upper limit of normal.
9. Patients who are therapeutically treated with an agent such as warfarin or heparin
will be allowed to receive either regorafenib or afatinib provided that their
medication dose and INR/PTT are stable. Close monitoring is mandatory if the patient
is receiving anticoagulants. If values are above the therapeutic range the
anticoagulant doses should be modified and assessments should be repeated until
10. Male patients with female partners of childbearing potential and women patients of
childbearing potential are required to use two forms of acceptable contraception,
including one barrier method, during their participation in the study and for 90 days
following last dose of study drug(s). Male patients must also refrain from donating
sperm during their participation in the study and for 90 days after the last dose of
11. Willingness and ability to comply with study and follow-up procedures.
12. Ability to understand the nature of this study and give written informed consent.
1. Two or more prior chemotherapy regimens in the metastatic setting.
2. Most recent chemotherapy ≤ 3 weeks and > Grade 1 chemotherapy-related side effects,
with the exception of neuropathy (> grade 2 excluded) and alopecia.
3. 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.
4. 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.
5. Major surgical procedures ≤28 days of beginning study drug, or minor surgical
procedures ≤7 days. No waiting required following port-a-cath placement.
6. 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 anticonvulsants are contraindicated.
7. Pregnant or lactating
8. Acute or chronic liver, renal, or pancreas disease.
9. Presence of active gastrointestinal disease or other condition that will interfere
significantly with the absorption, distribution, metabolism, or excretion of oral
10. 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
11. Inadequately controlled hypertension.
12. 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.
13. 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.
14. For patients receiving cabozantinib only: Do not administer cabozantinib to patients
that have high risk or at high risk for severe haemorrhage. Examples include:
1. The patient has radiographic evidence of cavitating pulmonary lesion(s).
2. The patient has tumor invading or encasing any major blood vessels.
3. The patient has had hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood within 3
months before the first dose of study treatment.
4. The patient has experienced clinically significant GI bleeding within 6 months of
the first dose of study treatment.
5. The patient has experienced any other signs indicative of pulmonary hemorrhage
within 3 months of the first dose of study treatment.
15. For patients receiving cabozantinib only: Do not administer cabozantinib to patients
that have high risk or at high risk of perforation or fistula:
1. The patient has evidence of tumor invading the GI tract, active peptic ulcer
disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis,
cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute
obstruction of the pancreatic duct or common bile duct, or gastric outlet
2. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess
within 6 months before first dose. Note: Complete healing of an intra-abdominal
abscess must be confirmed before first dose.
3. The patient has pre-existing fistula of head and neck area. Note: Treatment areas
should be healed with no sequelae from prior radiation therapy that would
predispose to fistula formation.
4. The patient has pre-existing osteonecrosis of the jaw.
16. Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet
inhibitors. [Patients receiving cabozantinib only]
17. Note: Low-dose aspirin for cardioprotection (per local applicable guidelines),
low-dose warfarin (< 1 mg/day), and low dose, low molecular weight heparins (LMWH) are
permitted. Anticoagulation with therapeutic doses of LMWH is allowed in subjects
without radiographic evidence of brain metastasis, who are on a stable dose of LMWH
for at least 12 weeks before randomization, and who have had no complications from a
thromboembolic event or the anticoagulation regimen.Presence of a non-healing wound,
non-healing ulcer, or bone fracture.
18. Patients with phaeochromocytoma.
19. 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
20. Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C.
21. 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
are eligible, as are patients with history of non-melanoma skin cancer.
22. 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: Sarah Cannon 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
|Medical College of Wisconsin
Milwaukee, Wisconsin 53226