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Non-small Cell Lung CarcinomaPhase 2NCT02795156

Study Assessing Activity of Molecularly Matched Targeted Therapies in Select Tumor Types Based on Genomic Alterations

A Phase 2 study testing Afatinib, Regorafenib and Cabozantinib in people with Non-small Cell Lung Carcinoma and Urothelial Carcinoma, run by SCRI Development Innovations, LLC at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Afatinib, Regorafenib and Cabozantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
8 sitesUnited States
Study dates
28 Sep 2016to 17 Aug 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 prolong survival:
  • Non-small cell lung cancer
  • Urothelial carcinoma
  • Non-colon gastrointestinal cancers (including hepatobiliary, pancreatic, and gastroesophageal tumors)
  • Upper aerodigestive tract cancers (including lip, tongue, salivary gland, gum, oral cavity, mouth, tonsils, oropharynx, nasopharynx, nasal cavity, sinus, and larynx tumors)
  • Patients must have a predefined genomic alteration that can be targeted with any of the FDA-approved targeted agents used in this study.
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  • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Age greater than or equal to 18 years.
  • Adequate hematologic function defined as:
  • Absolute neutrophil count (ANC) ≥1500/μL
  • Platelets ≥75,000/μL
  • 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 bilirubin)
  • 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.
  • 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 stable.
  • 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 study drug.
  • Willingness and ability to comply with study and follow-up procedures.
  • Ability to understand the nature of this study and give written informed consent.

Who cannot join

  • 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 anticonvulsants are contraindicated.
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  • 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.
  • 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 are eligible)
  • Valvular disease with significant compromise in cardiac function
  • Inadequately controlled hypertension.
  • 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.
  • For patients receiving cabozantinib only: Do not administer cabozantinib to patients that have high risk or at high risk for severe haemorrhage. Examples include:
  • The patient has radiographic evidence of cavitating pulmonary lesion(s).
  • The patient has tumor invading or encasing any major blood vessels.
  • The patient has had hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment.
  • The patient has experienced clinically significant GI bleeding within 6 months of the first dose of study treatment.
  • The patient has experienced any other signs indicative of pulmonary hemorrhage within 3 months of the first dose of study treatment.
  • For patients receiving cabozantinib only: Do not administer cabozantinib to patients that have high risk or at high risk of perforation or fistula:
  • 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 obstruction.
  • 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.
  • 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.
  • The patient has pre-existing osteonecrosis of the jaw.
  • Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors. [Patients receiving cabozantinib only]
  • 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.
  • 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 treatment.
  • Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis 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 are eligible, as are patients with history of non-melanoma skin cancer.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Tennesse Oncology

    Chattanooga, Tennessee, 37404

  • Sarah Cannon Research Institute at HealthOne

    Denver, Colorado, 80218

  • Florida Cancer Specialists - South

    Fort Myers, Florida, 33916

  • Research Medical Center - HCA Midwest

    Kansas City, Missouri, 64132

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Florida Cancer Specialists - North

    St. Petersburg, Florida, 33705

  • Florida Cancer Specialists - East

    West Palm Beach, Florida, 33401

Other trials in United States

About this study

Official title: Phase II Study to Evaluate the Activity of Commercially Available Molecularly Matched Targeted Therapies in Selected Tumor Types Based on Genomic Alterations

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.

Read the detailed description

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.

Being tested
Afatinib, Regorafenib, Cabozantinib
Keywords
regorafenib, afatinib, targeted therapy, cabozantinib
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AfatinibDrug

    Also called Gilotrif

    40 mg orally once daily for each 28-day cycle. Treatment will continue until disease progression or intolerable toxicity or other reason for discontinuation up to 45 months.

  • RegorafenibDrug

    Also called Stivarga

    160 mg orally once daily for the first 21 days of each 28-day cycle. Treatment will continue until disease progression or intolerable toxicity or other reason for discontinuation up to 45 months.

  • CabozantinibDrug

    Also called Cabometyx

    60 mg orally once daily for each 28-day cycle. Treatment will continue until disease progression or intolerable toxicity or other reason for discontinuation up to 45 months.

Study groups in NCT02795156
Study groupRoleWhat they receive
Arm 1ExperimentalPatients with non-small cell lung cancer who have failed first line treatment may receive either regorafenib (Stivarga), afatinib (Gilotrif), or cabozantinib (Cabometyx) at the recommended dose level, depending on their specific genomic alterations.
Receives: Drug: Afatinib; Drug: Regorafenib; Drug: Cabozantinib
Arm 2ExperimentalPatients with urothelial carcinoma who have failed first line treatment may receive either regorafenib (Stivarga), afatinib (Gilotrif), or cabozantinib (Cabometyx) at the recommended dose level, depending on their specific genomic alterations.
Receives: Drug: Afatinib; Drug: Regorafenib; Drug: Cabozantinib
Arm 3ExperimentalPatients with non-colon gastrointestinal cancers who have failed first line treatment may receive either regorafenib (Stivarga), afatinib (Gilotrif), or cabozantinib (Cabometyx) at the recommended dose level, depending on their specific genomic alterations.
Receives: Drug: Afatinib; Drug: Regorafenib; Drug: Cabozantinib
Arm 4ExperimentalPatients with upper aerodigestive tract cancers who have failed first line treatment may receive either regorafenib (Stivarga), afatinib (Gilotrif), or cabozantinib (Cabometyx) at the recommended dose level, depending on their specific genomic alterations.
Receives: Drug: Afatinib; Drug: Regorafenib; Drug: Cabozantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR) in Each Arm Receiving Targeted Therapy Based on Relevant Genomic Alterations

    ORR is defined as the percentage of patients with confirmed complete response (CR) or confirmed partial response (PR), i.e., two CRs and/or PRs at least 4 weeks apart, according to the RECIST v1.1 criteria. CR=disappearance of all target and non-target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: every 8 weeks until tumor progression or treatment discontinuation, up to 45 months.

Secondary outcomes (3)

  1. Clinical Benefit Rate in Each Arm Receiving Targeted Therapy Based on Relevant Genomic Alterations

    Clinical Benefit Rate (CBR) is defined as the percentage of patients with confirmed complete response (CR) or confirmed partial response (PR) or stable disease (SD) ≥ 6 months according to RECIST v1.1. Confirmed response is defined as two CRs and/or PRs at least 4 weeks apart, according to the RECIST v1.1 criteria. CR=disappearance of all target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Stable Disease= Neither sufficient shrinkage to qualify for PR nor sufficient increase of 20% in the sum of diameters or presence of a new lesion to qualify for progressive disease (PD), taking as reference the smallest (nadir) sum of diameters since the treatment started.

    Measured: Every 8 weeks until tumor progression or treatment discontinuation, up to 45 months

  2. Time to Treatment Failure (TTF) in Each Arm Receiving Targeted Therapy Based on Relevant Genomic Alterations

    Time to treatment failure is measured from the first day of treatment until the patient is removed from study for toxicity, disease progression per RECIST v1.1, patient choice, or death. Progressive disease (PD) per RECIST v1.1 is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest (nadir) sum since the treatment started, or the appearance of one or more new lesions. Requires not only 20% increase, but absolute increase of a minimum of 5 mm over the sum.

    Measured: Every 8 weeks until tumor progression or treatment discontinuation, up to 45 months

  3. Progression-Free Survival in Each Arm Receiving Targeted Therapy Based on Relevant Genomic Alterations

    Progression Free Survival (PFS) is defined as the time from the first day of study drug administration (Day 1) to disease progression as defined by the RECIST v1.1, or death on study. Patients who are alive and free from disease progression will be censored at the date of last tumor assessment. Progressive disease (PD) per RECIST v1.1 is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest (nadir) sum since the treatment started, or the appearance of one or more new lesions. Requires not only 20% increase, but absolute increase of a minimum of 5 mm over the sum.

    Measured: Every 8 weeks until tumor progression or treatment discontinuation, up to 45 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jun 2016 (estimated)
  2. Study start28 Sep 2016
  3. Primary completion17 Aug 2022
  4. Study completion17 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02795156
Sponsor's protocol ID
SCRI PRO 10
Status last verified
Aug 2023
First submitted
6 Jun 2016
Last updated
5 Dec 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Afatinib, Regorafenib and Cabozantinib in people with Non-small Cell Lung Carcinoma and Urothelial Carcinoma, run by SCRI Development Innovations, LLC at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) in Each Arm Receiving Targeted Therapy Based on Relevant Genomic Alterations (time frame: every 8 weeks until tumor progression or treatment discontinuation, up to 45 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02795156.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2023.

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