Clinical Trials /

Tucatinib With Chemotherapy and Trastuzumab in Advanced Her-2-neu Overexpressing, Previously Treated Breast Cancer.

NCT04896320

Description:

This is an open label study of tucatinib in combination with either vinorelbine or gemcitabine and trastuzumab in patients with metastatic HER2+ breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tucatinib With Chemotherapy and Trastuzumab in Advanced Her-2-neu Overexpressing, Previously Treated Breast Cancer.
  • Official Title: A Phase 1/2 Study of Tucatinib With Chemotherapy and Trastuzumab in Patients With Previously Treated, Advanced Her-2-Neu Overexpressing Breast Cancer.

Clinical Trial IDs

  • ORG STUDY ID: 2021000247
  • NCT ID: NCT04896320

Conditions

  • Breast Cancer Stage IV

Interventions

DrugSynonymsArms
TucatinibGemcitabine + Tucatinib + Trastuzumab

Purpose

This is an open label study of tucatinib in combination with either vinorelbine or gemcitabine and trastuzumab in patients with metastatic HER2+ breast cancer.

Detailed Description

      This phase I/II study will assess the recommended dosing of tucatinib in combination with
      trastuzumab and either vinorelbine or gemcitabine in patients with advanced, HER2+ breast
      cancer. The study will be conducted as a parallel cohort study looking at optimal dose and
      safety and efficacy.

      Arm 1 Gemcitabine + Tucatinib + Trastuzumab: Gemcitabine (1000 mg/m2) will be administered
      intravenously on Days 1 and 8. The investigational study drug (tucatinib) will be
      administered as 300mg by mouth taken twice a day of every day in each cycle. Trastuzumab will
      be administered per package insert on Day 1 of each cycle.

      Arm 2 Vinorelbine + Tucatinib + Trastuzumab: Vinorelbine (25 mg/m2) will be administered
      intravenously on Days 1 and 8 of each cycle. The investigational study drug (tucatinib) will
      be administered as 300mg by mouth twice a day of every day in each cycle. Trastuzumab will be
      administered per package insert on Day 1 of each 2 cycle.

      Note: Cycle length is 21 days.
    

Trial Arms

NameTypeDescriptionInterventions
Gemcitabine + Tucatinib + TrastuzumabExperimentalGemcitabine (1000 mg/m2) will be administered intravenously on Days 1 and 8 of each 21-day cycle. The investigational study drug (tucatinib) will be administered as 300mg by mouth taken twice a day of every day in each cycle. Trastuzumab will be administered per package insert on Day 1 of each cycle.
  • Tucatinib
Vinorelbine + Tucatinib + TrastuzumabExperimentalVinorelbine (25 mg/m2) will be administered intravenously on Days 1 and 8 of each 21-day cycle. The investigational study drug (tucatinib) will be administered as 300mg by mouth taken twice a day of every day in each cycle. Trastuzumab will be administered per package insert on Day 1 of each cycle.
  • Tucatinib

Eligibility Criteria

        Inclusion Criteria:

          1. Age >18, with metastatic breast cancer, documented Her2+ by FISH/Dual-ISH, and/or IHC
             3+ staining, local determination of Her2+ allowed

          2. Progressive disease with history of prior treatment with trastuzumab and capecitabine
             for metastatic disease (unless deemed intolerable or ineligible for capecitabine by
             the investigator).

          3. Prior treatment with T-DM1 in any setting unless deemed intolerable or ineligible for
             T-DM1 by the investigator.

          4. Target or non-target lesions per RECIST 1.1.

          5. ECOG 0 or 1.

          6. In the opinion of the investigator, life expectancy >6 months.

          7. LVEF > 50% by ECHO or MUGA within 4 weeks prior to first study treatment.

          8. Cr Clearance > 50mL/min per institutional guidelines.

          9. Negative serum pregnancy test for women of child bearing potential within 14 days of
             first study treatment and must agree to use effective contraception through 30 days
             after last treatment.

             For subjects who can father children:

               -  Must agree not to donate sperm starting at time of informed consent and
                  continuing throughout the study period and for at least 30 days after the final
                  study drug administration.

               -  If sexually active with a person of childbearing potential in a way that could
                  lead to pregnancy, must consistently use a barrier method of birth control
                  starting at time of informed consent and continuing throughout the study and for
                  at least 30 days after the final dose of study drug administration.

               -  If sexually active with a person who is pregnant or breastfeeding, must
                  consistently use a barrier method of birth control starting at time of informed
                  consent and continuing throughout the study and for at least 30 days after the
                  final dose of study drug administration.

         10. Willing and able to provide written Informed consent.

         11. All toxicities related to prior cancer therapies must have resolved to < grade 1, with
             following exceptions: alopecia, neuropathy, which must have resolved to <Grade 2;
             congestive heart failure which must have been <grade 1 in severity at the time of
             occurrence and resolved completely.

         12. Adequate hematologic and hepatic function as defined by:

               -  Hemoglobin >9g/dL

               -  Absolute neutrophil count (ANC)>1000 cells/uL

               -  Platelets >100,000/uL

               -  Total bilirubin < 1.5 X upper limit of normal (ULN), except for subjects with
                  known Gilbert's disease, who may enroll if the conjugated bilirubin is < 1.5 X
                  ULN

               -  Transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase
                  [AST/SGOT] and alanine aminotransferase/serum glutamic pyruvic transaminase
                  [ALT/SGPT]) ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases are present)

         13. CNS Inclusion - Based on screening contrast brain MRI, patients must have one of the
             following:

               -  No evidence of brain metastases

               -  Untreated brain metastases not needing immediate local therapy. For patients with
                  untreated CNS lesions > 2.0 cm on screening contrast brain MRI, discussion with
                  and approval from the medical monitor is required prior to enrollment

               -  Previously treated brain metastases

        A. Brain metastases previously treated with local therapy may either be stable since
        treatment or may have progressed since prior local CNS therapy, provided that there is no
        clinical indication for immediate re-treatment with local therapy in the opinion of the
        investigator.

        B. Patients treated with CNS local therapy for newly identified lesions found on contrast
        brain MRI performed during screening for this study may be eligible to enroll if all of the
        following criteria are met:

        i. Time since WBRT is ≥ 21 days prior to first dose of treatment, time since SRS is ≥ 7
        days prior to first dose of treatment, or time since surgical resection is ≥ 28 days ii.
        Other sites of disease assessable by RECIST 1.1 are present C. Relevant records of any CNS
        treatment must be available to allow for classification of target and non-target lesions

        Exclusion Criteria:

          1. Having previous treatment with vinorelbine and gemcitabine for metastatic disease.

          2. History of allergic reactions to trastuzumab except for grade 1/2 infusion reactions.

          3. History of allergic reactions to tucatinib.

          4. Any systemic anti-cancer therapy <14 days of first study treatment, including any
             experimental agents.

          5. Clinically significant cardiopulmonary disease including ventricular arrhythmia
             requiring therapy

               -  Uncontrolled hypertension (defined as persistent systolic blood pressure >
                  150mmHG and/or diastolic blood pressure >100mm Hg on antihypertensive medication)
                  or any history of symptomatic CHF

          6. Known history of HIV, Hep B/C or known chronic liver disease.

          7. Known MI or unstable angina in last 6 months prior to first study treatment

          8. Inability to swallow pills or significant GI disease, in the opinion of the
             Investigator that would preclude oral absorption of the medication.

          9. Are pregnant, breastfeeding, or planning pregnancy.

         10. CNS Exclusion - Based on screening brain MRI, patients must not have any of the
             following:

             A. Any untreated brain lesions > 2.0 cm in size, unless discussed with medical monitor
             and approval for enrollment is given.

             B. Ongoing use of systemic corticosteroids for control of symptoms of brain metastases
             at a total daily dose of > 2 mg of dexamethasone (or equivalent). However, patients on
             a chronic stable dose of ≤ 2 mg total daily of dexamethasone (or equivalent) may be
             eligible with discussion and approval by the medical monitor.

             C. Any brain lesion thought to require immediate local therapy, including (but not
             limited to) a lesion in an anatomic site where increase in size or possible
             treatment-related edema may pose risk to patient (e.g. brain stem lesions). Patients
             who undergo local treatment for such lesions identified by screening contrast brain
             MRI may still be eligible for the study based on criteria described under CNS
             inclusion criteria.

             D. Known or suspected LMD as documented by the investigator. E. Have poorly controlled
             (> 7days) generalized or complex partial seizures, or manifest neurologic progression
             due to brain metastases notwithstanding CNS-directed therapy

         11. Use of a strong CYP3A4 or CYP2C8 inhibitor within ≤14days, or use of a strong CYP3A4
             or CYP2C8 inducer within ≤5 days prior to the first study treatment. CYP3A4 or CYP2C8
             inducers and inhibitors are also prohibited as concomitant medications within ≤14 days
             of initiating Tucatinib treatment. . Use of sensitive CYP3A substrates should be
             avoided two weeks before enrollment and during study treatment. See Appendices C, D, E
             for references. (See Section 7.6 for additional prohibited concomitant medications)

         12. Prior radiation therapy less than 7 days from start of treatment.

         13. Other medical, social, or psychosocial factors that, in the opinion of the
             investigator, could impact safety or compliance with study procedures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the maximum tolerated dose and recommended dosing of tucatinib to be given in combination with either vinorelbine or gemcitabine and trastuzumab.
Time Frame:Cycle 1 Day 1 (each cycle is 21 days) to 30 Day Safety Follow-Up (after treatment), approximately 14 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Study Treatment-Related Adverse Events
Time Frame:Cycle 1 Day 1 (each cycle is 21 days) to 30 Day Safety Follow-Up, approximately 14 weeks
Safety Issue:
Description:Number of participants given tucatinib in combination with vinorelbine or gemcitabine with trastuzumab with treatment-related adverse events as assessed by CTCAE v5.0 with Her-2-neu overexpressing metastatic breast cancer.
Measure:Overall Response Rate
Time Frame:Up to 5 Years
Safety Issue:
Description:Number of patients who have a partial or complete response to treatment per RECIST 1.1.
Measure:Progression Free Survival
Time Frame:Up to 5 Years
Safety Issue:
Description:Length of time from start of study treatment to disease progression or death from any cause.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Providence Health & Services

Trial Keywords

  • Metastatic
  • Her2+
  • Trastuzumab
  • Tucatinib

Last Updated

May 21, 2021