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History of Changes for Study: NCT04172597
A Phase 2 Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies
Latest version (submitted June 10, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 November 19, 2019 None (earliest Version on record)
2 November 25, 2019 Arms and Interventions, Study Design, Study Status and Study Identification
3 December 10, 2019 Study Status and Oversight
4 January 23, 2020 Recruitment Status, Study Status and Contacts/Locations
5 March 10, 2020 Contacts/Locations and Study Status
6 August 6, 2020 Study Status and Contacts/Locations
7 September 14, 2020 Contacts/Locations and Study Status
8 November 11, 2020 Study Status and Contacts/Locations
9 June 14, 2021 Study Status
10 June 10, 2022 Recruitment Status, Study Status, Arms and Interventions, Study Design, Contacts/Locations, Outcome Measures, Study Description, Eligibility, Conditions and Study Identification
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Study NCT04172597
Submitted Date:  November 19, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: SPI-POZ-203
Brief Title: A Phase 2 Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies
Official Title: A Phase 2 Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies
Secondary IDs:
Open or close this module Study Status
Record Verification: November 2019
Overall Status: Not yet recruiting
Study Start: December 2019
Primary Completion: June 2023 [Anticipated]
Study Completion: December 2023 [Anticipated]
First Submitted: November 19, 2019
First Submitted that
Met QC Criteria:
November 19, 2019
First Posted: November 21, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
November 19, 2019
Last Update Posted: November 21, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Spectrum Pharmaceuticals, Inc
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: This is a Phase 2, open-label, multicenter study to evaluate the efficacy and the safety/tolerability of poziotinib in five patient cohorts for up to 150 previously treated patients with any systemic therapy (Cohort 1: 30 Patients that have HER2-positive or HER2-negative breast cancer with HER2 activating mutations, Cohort 2: 30 Patients that have colorectal cancer with HER2 activating mutations, Cohort 3: Patients that have solid tumors (except NSCLC, breast cancer, or colorectal cancer) with HER2 activating mutations, Cohort 4: 30 Patients that have high-grade glioma with EGFR activating mutations, and Cohort 5: 30 Patients that have solid tumors (except NSCLC or high-grade glioma) with EGFR activating mutations.
Detailed Description:

The Screening period (Day -30 to Day 1) lasts up to approximately 30 days prior to Cycle 1, Day 1. Patients must meet all Inclusion/Exclusion Criteria to participate in the study. Eligible patients will provide written Informed Consent prior to undergoing any study procedures.

Each treatment cycle is 28 calendar days in duration. There will be five patient cohorts and eligible patients will be enrolled into each cohort in parallel based on EGFR or HER2 exon 20 mutation status and prior treatment status:

  • Cohort 1: Patients that have HER2-positive or HER2-negative breast cancer with HER2 activating mutations.
  • Cohort 2: Patients that have colorectal cancer with HER2 activating mutations
  • Cohort 3: Patients that have solid tumors (except NSCLC, breast cancer, or colorectal cancer) with HER2 activating mutations
  • Cohort 4: Patients that have high-grade glioma with EGFR activating mutations
  • Cohort 5: Patients that have solid tumors (except NSCLC or high-grade glioma) with EGFR activating mutations

All patients will be treated 28 days per cycle until 24 months of treatment, disease progression, death, intolerable adverse events (AEs), or other protocol-specified reasons for patient withdrawal

Open or close this module Conditions
Conditions: Breast Cancer
Colorectal Cancer
Solid Tumor
High Grade Glioma
Keywords: EGFR activating mutations
HER2 activating mutations
HER2-positive breast cancer
HER2-negative breast cancer
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Each treatment cycle is 28 calendar days in duration. This is a basket study with five patient cohorts and eligible patients will be enrolled into each cohort in parallel based on EGFR or HER2 mutation-positive malignant solid tumors status.
Number of Arms: 5
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 150 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Cohort 1
Patients that have HER2-positive or HER2-negative breast cancer with HER2 activating mutations
Drug: Poziotinib Hydrochloride
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
Experimental: Cohort 2
Patients that have colorectal cancer with HER2 activating mutations
Drug: Poziotinib Hydrochloride
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
Experimental: Cohort 3
Patients that have solid tumors (except NSCLC, breast cancer, or colorectal cancer) with HER2 activating mutations
Drug: Poziotinib Hydrochloride
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
Experimental: Cohort 4
Patients that have high-grade glioma with EGFR activating mutations
Drug: Poziotinib Hydrochloride
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
Experimental: Cohort 5
Patients that have solid tumors (except NSCLC or high-grade glioma) with EGFR activating mutations
Drug: Poziotinib Hydrochloride
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Objective Response Rate (ORR)
[ Time Frame: 24 months ]

Proportion of patients whose best overall response is confirmed CR or PR
Secondary Outcome Measures:
1. Duration of Response (DoR)
[ Time Frame: 24 months ]

Time from the first CR or PR until progressive disease or death
2. Disease Control Rate (DCR)
[ Time Frame: 24 months ]

Proportion of patients whose best overall response is CR, PR, or SD
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Key Inclusion Criteria:

  1. Patient is 18 years or older.
  2. Patient must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements
  3. Patient has a metastatic solid tumor that meets at least one of the following criteria:
    • has progressed on a standard therapy
    • has no available standard therapy
    • In the opinion of the investigator, patient is not a candidate for or would be unlikely to tolerate or receive benefit from standard therapy
  4. Patient is positive for EGFR or HER2 mutations based on DNA genetic testing of either tumor tissue or plasma samples, but tissue is preferred. Patients with documented EGFR or HER2 mutations are identified by local testing from participating sites using next generation sequencing (NGS) test. Patient with a solid tumor with at least one of the listed activating mutations.
    • Cohort 1: Patients that have breast cancer with HER2 activating mutations (N=30)
    • Cohort 2: Patients that have colorectal cancer with HER2 activating mutations (N=30)
    • Cohort 3: Patients that have solid tumors (except NSCLC, breast cancer, or colorectal cancer) with HER2 activating mutations (N=30)
    • Cohort 4: Patients that have high-grade glioma with EGFR activating mutations (N=30)
    • Cohort 5: Patients that have solid tumors (except NSCLC or high-grade glioma) with EGFR activating mutations (N=30)

    Activating Mutations Cohorts 1-3. HER2 Activating Mutations (at least one of the following) Furin-Like/Extracellular. S310F/Y Transmembrane. I655V, V659E, R678Q, V697L Kinase Domain. Exon 20 insertion, T733I, L755X, I767M, D769H/N/Y, V773M, V777L/M, L786V, V842I, T862I, L869R

    Cohorts 4-5. EGFR Activating Mutations (at least one of the following) Extracellular & Transmembrane: EGFRvIII, R108K, R222C, A289T, P596L, G598V Kinase Domain: Exon 20 insertion, E709K, G719X, V742I, E746_A750del, S768I, V769M, V774M, R831C, R831H, L858R, L861Q, A864V

  5. Patient has measurable disease, as per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and/or RANO Criteria for Cohort 4. These target lesion(s) must be radiographically measurable. CNS metastatic lesions cannot be considered target lesions in Cohorts 1-3 and in Cohort 5.
  6. Brain metastases may be allowed if patient's condition is stable. Stable brain metastases are defined as stable symptoms, no requirement for high dose or increasing doses of systemic corticosteroid (except Cohort 4 where anti-seizure medication [Keppra] and dexamethasone up to or equivalent to 4 mg daily), nor progression on imaging studies for at least 4 weeks prior to enrolment.
  7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  8. Patient has recovered from prior systemic therapy for metastatic disease to Grade ≤1 for non-hematologic toxicities (except for Grade ≤2 peripheral neuropathy) and has adequate hematologic, hepatic, and renal function at Baseline, as defined by:
    • Absolute neutrophil count (ANC) must be ≥1.0×109/L
    • Platelet count ≥ 75 × 109/L
    • Hemoglobin ≥ 9.0 g/dL
    • Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT) ≤2.5 ×upper limit of normal (ULN); if hepatic metastases are present, ≤5.0×ULN
    • Creatinine clearance ≥ 50 mL/min (calculated according to Cockcroft and Gault formula)

Exclusion Criteria:

  1. Patient has primary tumors in central nervous system (CNS) or in brain, including glioblastoma multiforme (GBM), meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or unstable brain metastasis except if qualified under inclusion criteria for Cohort 4.
  2. Patient with T798M or T798I mutations in HER2, or patients with the T790M mutation in EGFR.
  3. Patients with breast or gastric cancers with HER2 copy number alterations/amplifications/over expressions and no HER2 activating mutations.
  4. Patient has received anticancer chemotherapy, biologics, immunotherapy, targeted therapy (including HER2 targeted therapy), curative-intent radiotherapy, or other investigational treatment within 15 days. Local radiation therapy for bone pain may be allowed. Standard and approved hormonal therapies for hormonal receptor positive tumors are allowed.
  5. Patient has not recovered (i.e, still at > Grade 1) from drug-induced pancreatitis or has a history of drug-induced pancreatitis.
  6. Patient has not recovered (i.e, still at > Grade 1) from interstitial lung disease or has a history of interstitial lung disease or radiation pneumonitis.
  7. Patient has a history of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.
  8. Patient has a high risk of cardiac disease, as determined by the Investigator, may undergo either echocardiogram (ECHO) or multi-gated acquisition (MUGA) during Screening and has a cardiac ejection fraction <50%.
  9. Patient has a history of other malignancies within the last 3 years, except for non-melanoma skin cancer, carcinoma in situ of the cervix, or PSA-stable, asymptomatic, early stage of prostate cancer or superficial bladder cancer without active treatment.
  10. Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function or malabsorption syndrome.
  11. Patient has an active liver disease or biliary tract disease (except for Gilbert's disease, asymptomatic biliary stones, liver metastasis, or stabilized chronic liver diseases).
  12. Patient has a medical condition that in the opinion of the investigator or medical monitor would put her/him at an unreasonable risk including drug toxicity during the trial.
  13. Patient has had recent major surgery or invasive procedure within 15 days prior to starting study treatment.
Open or close this module Contacts/Locations
Central Contact Person: Bill Paxton, MD PhD
Telephone: 949-743-9259
Email: SPI-POZ-203Basket@sppirx.com
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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