Clinical Trials /

Phase 2 Study of TVB-2640 in KRAS Non-Small Cell Lung Carcinomas

NCT03808558

Description:

This is a prospective one arm, single center phase 2 trial of TVB-2640 in KRaS mutant nSCLC patients. 12 patients will be treated with a minimum of 1 cycle of TVB-2640 therapy over 8 weeks.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Study of TVB-2640 in KRAS Non-Small Cell Lung Carcinomas
  • Official Title: A Phase 2 Single-Center Pharmacodynamic Study of TVB-2640 In KRAS Mutant Non-Small Cell Lung Carcinomas

Clinical Trial IDs

  • ORG STUDY ID: STU 022017-058
  • NCT ID: NCT03808558

Conditions

  • KRAS Gene Mutation

Interventions

DrugSynonymsArms
TVB-2640TVB-2640

Purpose

This is a prospective one arm, single center phase 2 trial of TVB-2640 in KRaS mutant nSCLC patients. 12 patients will be treated with a minimum of 1 cycle of TVB-2640 therapy over 8 weeks.

Detailed Description

      This is a prospective one arm, single center phase 2 trial of TVB-2640 in KRaS mutant nSCLC
      patients. 12 patients will be treated with a minimum of 1 cycle of TVB-2640 therapy over 8
      weeks. Patients with stable disease or partial/complete remissions will continue therapy. The
      endpoints are response rate-RR, disease control rate-DCR, PFS-progression-free survival,
      CTCaev4.03 toxicities, plasma lipid levels and 11C-acetate PeT tumor imaging.

      Primary endpoints are ReCiST v1.1 best response and response duration and nCi CTCaev4.1
      toxicity profile over eight weeks. Secondary endpoints are 11C-acetate tumor uptake
      pretreatment and at four weeks of treatment and plasma lipidomics pretreatment and at four
      weeks of treatment.
    

Trial Arms

NameTypeDescriptionInterventions
TVB-2640ExperimentalPatients will be administered TVB-2640 100mg/m2 orally once a day for 8 weeks.
  • TVB-2640

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed metastatic or advanced-stage KRAS mutant
             NSCLC that is refractory, relapsed, and intolerant of combination chemotherapy and
             subsequential immune checkpoint therapy.

          2. Patient has progressive disease.

          3. Patient has measurable disease by RECIST v1.1 (Eisenhauer, 2009).

          4. Age ≥ 18 years.

          5. ECOG performance status of 0 or 1.

          6. Predicted life expectancy of >3 months.

          7. Adequate organ and marrow function as defined below:

        1. - absolute neutrophil count ≥ 1,500/mcL 2. - platelets ≥ 100,000/mcL 3. - total
        bilirubin <2X institutional upper limit of normal 4. - AST and ALT ≤5X institutional upper
        limit of normal 5. - creatinine <1.5X institutional upper limit of normal 6. -LVEF >50% 7.
        -QTcF <470msec

        8. Women of child-bearing potential and men must agree to use adequate contraception
        (hormonal or barrier method of birth control; abstinence) prior to study entry, for the
        duration of study participation, and for 90 days following completion of therapy. Should a
        woman become pregnant or suspect she is pregnant while participating in this study, she
        should inform her treating physician immediately.

        1. 3.1.6.1 A female of child-bearing potential is any woman (regardless of sexual
        orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets
        the following criteria:

        9. Has not undergone a hysterectomy or bilateral oophorectomy; or 10. Has not been
        naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any
        time in the preceding 12 consecutive months).

        11. No significant ischemic heart disease or myocardial infarction within 6 months of first
        dose of TVB-2640 and with current adequate cardiac function as in 3.1.7.

        12. Ability to understand and the willingness to sign a written informed consent.

        Exclusion Criteria

          1. Patient is unable to swallow oral medications or has impairment of GI function or GI
             disease that may significantly alter drug absorption such as active inflammatory bowel
             disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome.

          2. Patient has a history of risk factors for torsade de pointes such as heart failure,
             severe hypokalemia with potassium less than 3mM/L, family history of long QT syndrome
             or require use during study participation of concomitant medications known to prolong
             QT/QTc interval—see http://crediblemeds.org/everyone/
             composite-list-all-qtdrugs/?rf=US.

          3. Patients who require use of strong CYP3A4/5 agonists or inhibitors during study
             participation.

          4. Patient has uncontrolled or severe intercurrent medical condition including
             uncontrolled brain metastases. Patients with stable brain metastases either treated or
             being treated with a stable dose of steroids/anticonvulsants, with no dose change
             within 4 weeks before the first dose of TVB-2640, and no anticipated dose change, are
             allowed.

          5. Patient underwent major surgery within 4 weeks before the first dose of TVB-2640 or
             received cancer-directed therapy either chemotherapy, radiotherapy, hormonal therapy,
             biologic or immunotherapy, etc. or an investigational drug or device within 4 weeks
             and 6 weeks for mitomycin C and nitrosoureas or 5 half-lives of that agent whichever
             is shorter before the first dose of TVB-2640. A minimum of 10 days between termination
             of the investigational drug and administration of TVB-26740 is required. In addition,
             any drug-related toxicity, with the exception of alopecia, should have recovered to
             <Grade 1.

          6. If female, patient is pregnant or breast-feeding.

          7. Patient has evidence of a serious active infectioninfection requiring treatment with
             intravenous antibiotics.

          8. Patient has known immunodeficiency virus—HIV or hepatitis B or C infection, as such
             patients may be at increased risk for toxicity due to concomitant treatment and
             disease-related symptoms may preclude accurate assessment of the safety of TVB-2640.

          9. Patient has an important medical illness or abnormal laboratory finding that, in the
             Investigator's opinion, would increase the risk of participating in this study.

         10. Patient has a history of other malignancy treated with curative intent within the
             previous 5 years with the exception of adequately treated non-melanoma skin cancer or
             carcinoma in situ of the cervix.or breast. Subjects with previous invasive cancers are
             eligible if the treatment was completed more than 5 years prior to initiating current
             study treatment, and there is no evidence of recurrent disease.

         11. Patient has a history of clinically significant abnormality on slit-lamp examination
             or other clinically significant ophthalmologic finding, as determined by an
             ophthalmologist.

         12. Patient has a known allergy or hypersensitivity to components of TVB-2640.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the Preliminary disease control rate of TVB-2640 in KRAS mutant NSCLC
Time Frame:every 8 weeks through study completion, an average of 1 year
Safety Issue:
Description:Determine Disease control rate and response rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile.

Secondary Outcome Measures

Measure:Characterize the safety profile of TVB-2640 in KRAS mutant NSCLC patients.
Time Frame:Pretreatment and four weeks of treatment.
Safety Issue:
Description:Secondary endpoints are 11C-acetate tumor uptake pretreatment and at four weeks of treatment and plasma lipidomics pretreatment and at four weeks of treatment.
Measure:Establish the predictive value of 11C-acetate PET
Time Frame:Pretreatment and four weeks of treatment.
Safety Issue:
Description:To establish the predictive value of 11C-acetate PET pretreatment and post-treatment tumor uptake for disease control rate and response rate
Measure:Examine plasma lipidomics and assess relationship
Time Frame:Pretreatment and four weeks of treatment.
Safety Issue:
Description:Examine plasma lipidomics pretreatment and post-treatment and assess relationship to disease control rate, Complete response, response rate, and 11C-acetate PET uptake.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

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