Phase II Study to Evaluate the Activity of Commercially Available Molecularly Matched Targeted Therapies in Selected Tumor Types Based on Genomic Alterations
Overview
- Phase
- Phase 2
- Intervention
- Afatinib
- Conditions
- Non-small Cell Lung Carcinoma
- Sponsor
- SCRI Development Innovations, LLC
- Enrollment
- 100
- Locations
- 8
- Primary Endpoint
- Overall Response Rate (ORR) in Each Arm Receiving Targeted Therapy Based on Relevant Genomic Alterations
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •Age greater than or equal to 18 years.
- •Adequate hematologic function defined as:
Exclusion Criteria
- •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:
Arms & Interventions
Arm 1
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.
Intervention: Afatinib
Arm 1
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.
Intervention: Regorafenib
Arm 1
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.
Intervention: Cabozantinib
Arm 2
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.
Intervention: Afatinib
Arm 2
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.
Intervention: Regorafenib
Arm 2
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.
Intervention: Cabozantinib
Arm 3
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.
Intervention: Afatinib
Arm 3
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.
Intervention: Regorafenib
Arm 3
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.
Intervention: Cabozantinib
Arm 4
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.
Intervention: Afatinib
Arm 4
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.
Intervention: Regorafenib
Arm 4
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.
Intervention: Cabozantinib
Outcomes
Primary Outcomes
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.
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.
Secondary Outcomes
- 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)