Clinical trial NCT03281824: Clinical Study of ALT-P7 to Determine Safety, Tolerability and Pharmacokinetics in Breast Cancer Patients
Official title: Open-Label, Dose Increase and Phase I Study of ALT-P7 to Determine Safety, Tolerability, Pharmacokinetics for HER2 Positive Metastatic Breast Cancer Patients Who Have Progressed on Previous Trastuzumab-Based Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HER2-positive Breast Cancer
Keywords: HER2 Positive Breast Cancer
ALT-P7
Antibody-Drug Conjugate
Lead sponsor: Alteogen, Inc.
Sponsor class: INDUSTRY
First posted: 2017-09-13
Enrollment: 27
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This open-label study assessed the safety, tolerability and pharmacokinetics of ALT-P7(HM2-Drug Conjugate) in patients with HER2-positive metastatic breast cancer who have progressed on previous Trastuzumab-based therapy. Patients received ALT-P7(0.3 mg/kg\~5.4 mg/kg, 7 groups) intravenously on Day 1 of each 3-week cycle.


Eligibility criteria: Inclusion Criteria:

1. Patient who voluntarily signed the agreement
2. Adult patients ≥ 19 years of age
3. Eastern Cooperative Oncology Group(ECOG) Performance status of 0 or 1
4. Appropriate organism function proven by the following laboratory test results

   * Absolute neutrophil count ≥ 1500 cells/mm³
   * Platelets ≥ 100,000 cells/mm³
   * Hemoglobin ≥ 9.0 g/dL

     * Patients can receive red blood cell transfusions at this level.
   * Creatinine ≤ 1.5 × Upper Limit of Normal(ULN)
   * Aspartate Transaminase(AST) and Alanine Transaminase(ALT) ≤ 2.5 × ULN
   * Alkaline phosphatase ≤ 2.5 × ULN

     * Patients with liver and/or bone metastases: AST and ALT ≤ 5 × ULN, Alkaline phosphatase ≤ 5 × ULN
   * Albumin ≥ 3.0 g/dL, Total bilirubin ≤ 2.0 mg/dL
   * International Normalized Ratio(INR) \< 1.5 × ULN(Except when you are on therapeutic anticoagulation therapy)
5. It should be negative in serum pregnancy test in the case of pre-menopausal women and women who were menopausal for less than 12 months
6. In the case of a fertile woman, it should be negative in pregnancy test, and all men and women should use effective contraceptive methods while enrolled in this study. You must also agree to continue the contraception during the trial and up to 6 months after the last dose of the test
7. Those who are expected to understand and observe the clinical trial plan according to the tester's judgment
8. Those who voluntarily agreed to participate in this clinical trial and signed the agreement

Exclusion Criteria:

* Criteria for disease

  1. Previous history of intolerance to Trastuzumab including Grade 3-4 infusion reaction or hypersensitivity
  2. Previous history of permanent discontinuation of Trastuzumab due to the toxicity
  3. A person who has untreated or symptomatic brain metastasis, or brain metastasis requiring radiation, surgery or corticosteroid therapy to control the brain metastases within 4 weeks of the first administration
  4. Current Grade ≥ 2 (according to National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE) v4.03 of peripheral neuropathy
  5. If the toxicity of the previous treatment is not recovered to baseline level or lower than Grade 1 except for hair loss and peripheral neuropathy
  6. Hypercalcemia requiring bisphosphonate therapy (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN) However, it is allowed if bisphosphonate has been used for bone metastasis
  7. A person who has received clinical trial material, chemotherapy, hormone therapy, radiotherapy, immunotherapy or biological therapy within 3 weeks of the first administration. However, it is required a minimum of 2 weeks after surgery if stereotactic radiosurgery is performed
  8. Previous history of exposure to the cumulative dose of anthracycline (Doxorubicin \> 360 mg/m², Epirubicin \> 600 mg/m²)
* Criteria for cardio pulmonary function

  1. Unstable ventricular arrhythmia requiring treatment
  2. Previous history of symptomatic congestive heart failure (NYHA Class II-IV)
  3. Previous history of myocardial infarction or unstable angina within 6 months
  4. Cardiac troponin I ≥ 0.2 ng/mL
  5. A person who has inadequate left ventricular ejection fraction(LVEF) within 3 weeks of the first administration, LVEF \<50% by echocardiography or Multiple-gated Acquisition(MUGA)
  6. A person who has severe dyspnea or pneumonia requiring continuous oxygen therapy
* Common criteria

  1. Pregnant or breastfeeding
  2. A person who has undergone surgical operation or significant traumatic injury within 30 days before registration, or is expected to require surgical operation during the clinical trial
  3. Previous history of malignant tumors other than breast cancer within 5 years prior to screening (patient who can participate: squamous cell and basal cell carcinoma of the skin, intraepithelial cancer of the cervix, thyroid papillary cancer, or if the tester considers that the risk of relapse is minimum(regard as full recovery) and the sponsor agrees with it)
  4. A person who needs chronic corticosteroid therapy (≥ 10 mg/day prednisone or equivalent volume of other anti-inflammatory corticosteroids)
  5. If the result of human immunodeficiency virus (HIV), active hepatitis B or hepatitis C is positive during screening
  6. Patients with uncontrolled concomitant illnesses, including mental illness/social conditions, which may affect compliance with clinical trial procedures

Primary outcomes:
measure: DLT test
timeFrame: 21 days after first administration
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: up to 4 weeks
measure: Pharmacokinetics test
timeFrame: up to 4 weeks
measure: Immunogenicity test
timeFrame: up to 4 weeks
measure: Efficacy test
timeFrame: At the end of Cycle 2 (each cycle is 21 days)
Other outcomes:
Locations:
city: Daejeon
country: Korea, Republic of
facility: Alteogen
Study officials:
References: