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

NCT04896320 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 2021000247
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Breast Cancer Stage IV

Keywords

Metastatic; Her2+; Trastuzumab; Tucatinib

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose and recommended dosing of tucatinib to be given in combination with either vinorelbine or gemcitabine and trastuzumab.

  Cycle 1 Day 1 (each cycle is 21 days) to 30 Day Safety Follow-Up (after treatment), approximately 14 weeks

Secondary Outcomes (3)

• Study Treatment-Related Adverse Events

  Cycle 1 Day 1 (each cycle is 21 days) to 30 Day Safety Follow-Up, approximately 14 weeks

• Overall Response Rate

  Up to 5 Years

• Progression Free Survival

  Up to 5 Years

Study Arms (2)

Gemcitabine + Tucatinib + Trastuzumab

EXPERIMENTAL

Gemcitabine (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.

Drug: Tucatinib

Vinorelbine + Tucatinib + Trastuzumab

EXPERIMENTAL

Vinorelbine (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.

Drug: Tucatinib

Interventions

Tucatinib DRUG

Tucatinib is a highly selective, oral, reversibly Her2 small molecule tyrosine kinase inhibitor (TKI).

Gemcitabine + Tucatinib + Trastuzumab; Vinorelbine + Tucatinib + Trastuzumab

Eligibility Criteria

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

You may qualify if:

• Age \>18, with metastatic breast cancer, documented Her2+ by FISH/Dual-ISH, and/or IHC 3+ staining, local determination of Her2+ allowed
• Progressive disease with history of prior treatment with trastuzumab and capecitabine for metastatic disease (unless deemed intolerable or ineligible for capecitabine by the investigator).
• Prior treatment with T-DM1 in any setting unless deemed intolerable or ineligible for T-DM1 by the investigator.
• Target or non-target lesions per RECIST 1.1.
• ECOG 0 or 1.
• In the opinion of the investigator, life expectancy \>6 months.
• LVEF \> 50% by ECHO or MUGA within 4 weeks prior to first study treatment.
• Cr Clearance \> 50mL/min per institutional guidelines.
• 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.
• Willing and able to provide written Informed consent.
• 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.

You may not qualify if:

• Having previous treatment with vinorelbine and gemcitabine for metastatic disease.
• History of allergic reactions to trastuzumab except for grade 1/2 infusion reactions.
• History of allergic reactions to tucatinib.
• Any systemic anti-cancer therapy \<14 days of first study treatment, including any experimental agents.
• 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
• Known history of HIV, Hep B/C or known chronic liver disease.
• Known MI or unstable angina in last 6 months prior to first study treatment
• Inability to swallow pills or significant GI disease, in the opinion of the Investigator that would preclude oral absorption of the medication.
• Are pregnant, breastfeeding, or planning pregnancy.
• 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.
• 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
• 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)
• Prior radiation therapy less than 7 days from start of treatment.

Sponsors & Collaborators

• Providence Health & Services: lead
• Seagen Inc.: collaborator

Study Sites (4)

Providence Cancer Institute - Clackamas Clinic

Clackamas, Oregon, 97015, United States

Location

Providence Newberg Medical Center

Newberg, Oregon, 97132, United States

Location

Portland Providence Medical Center

Portland, Oregon, 97213, United States

Location

Providence St. Vincent Medical Center

Portland, Oregon, 97225, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

tucatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alison Conlin, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 21, 2021
• Study Start: December 15, 2021
• Primary Completion: June 19, 2023
• Study Completion: June 19, 2023
• Last Updated: June 22, 2023

Record last verified: 2023-06

Locations

US (4)