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

NCT02795156 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SCRI PRO 10
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 8

Brief 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. 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.

Conditions

Non-small Cell Lung Carcinoma; Urothelial Carcinoma; Gastrointestinal Carcinoma, Non-colon; Upper Aerodigestive Tract Carcinoma

Keywords

regorafenib; afatinib; targeted therapy; cabozantinib

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (3)

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

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

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

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

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

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

Study Arms (4)

Arm 1

EXPERIMENTAL

Patients 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.

Drug: Afatinib; Drug: Regorafenib; Drug: Cabozantinib

Arm 2

EXPERIMENTAL

Patients 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.

Drug: Afatinib; Drug: Regorafenib; Drug: Cabozantinib

Arm 3

EXPERIMENTAL

Patients 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.

Drug: Afatinib; Drug: Regorafenib; Drug: Cabozantinib

Arm 4

EXPERIMENTAL

Patients 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.

Drug: Afatinib; Drug: Regorafenib; Drug: Cabozantinib

Interventions

Afatinib DRUG

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.

Also known as: Gilotrif

Arm 1; Arm 2; Arm 3; Arm 4

Regorafenib DRUG

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.

Also known as: Stivarga

Arm 1; Arm 2; Arm 3; Arm 4

Cabozantinib DRUG

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.

Also known as: Cabometyx

Arm 1; Arm 2; Arm 3; Arm 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Foundation Medicine: collaborator
• Boehringer Ingelheim: collaborator
• Bayer: collaborator
• Exelixis: collaborator

Study Sites (8)

Sarah Cannon Research Institute at HealthOne

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists - South

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists - North

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists - East

West Palm Beach, Florida, 33401, United States

Location

Research Medical Center - HCA Midwest

Kansas City, Missouri, 64132, United States

Location

Tennesse Oncology

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell

Interventions

Afatinib; regorafenib; cabozantinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Sarah Cannon Development Innovations, LLC
• Organization: Sarah Cannon Development Innovations, LLC

CANN.InnovationsMedical@sarahcannon.com

844-710-6157

Study Officials

• Howard A. Burris, III, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2016
• First Posted: June 9, 2016
• Study Start: September 28, 2016
• Primary Completion: August 17, 2022
• Study Completion: August 17, 2022
• Last Updated: December 5, 2023
• Results First Posted: September 15, 2023

Record last verified: 2023-08

Locations

US (8)