Clinical Trials /

ORIN1001 in Patients With Advanced Solid Tumors and Relapsed Refractory Metastatic Breast Cancer

NCT03950570

Description:

This study evaluates the anti-tumor effects of ORIN 1001 in patients with advanced solid tumors and relapsed refractory (patients with progressive disease after receiving at least two lines of therapy in the advanced setting) metastatic breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: ORIN1001 in Patients With Advanced Solid Tumors and Relapsed Refractory Metastatic Breast Cancer
  • Official Title: A Phase 1, Open Label, Dose-Escalation and Expansion Study of Oral ORIN1001 With and Without Chemotherapy in the Treatment of Subjects With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ORIN1001-001
  • NCT ID: NCT03950570

Conditions

  • Solid Tumor
  • Breast Cancer Metastatic

Interventions

DrugSynonymsArms
PaclitaxelORIN1001Dose Escalation

Purpose

This study evaluates the anti-tumor effects of ORIN 1001 in patients with advanced solid tumors and relapsed refractory (patients with progressive disease after receiving at least two lines of therapy in the advanced setting) metastatic breast cancer.

Detailed Description

      This is a first in human, Phase 1, open label, dose escalation and dose expansion study that
      consists of two stages: A dose escalation stage to determine the MTD/RP2D of ORIN1001 when
      given as a single agent in up to 30 subjects with advanced solid tumors. In addition, a dose
      escalation stage to determine the MTD/RP2D of daily ORIN1001 in combination with paclitaxel
      given intravenously at 175 mg/m2 in up to 18 subjects with relapsed refractory metastatic
      breast cancer (TNBC, MYC+, or ER+ HER2-) . An expansion stage of ORIN1001 alone (Cohort A:
      TNBC) and in combination with paclitaxel (Cohorts B: MYC+; Cohort C: ER+ HER2-, and Cohort D:
      TNBC) to estimate efficacy in up to 120 subjects with relapsed refractory.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalRelapsed refractory metastatic breast cancer who are triple negative and treated with single agent ORIN1001. Relapsed refractory metastatic breast cancer that are MYC+ and treated with combination.
  • Paclitaxel
Dose ExpansionExperimentalRelapsed refractory metastatic breast cancer that are ER+ HER2- and treated with combination. Relapsed refractory metastatic breast cancer that are Triple Negative and treated with combination
  • Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

        For dose escalation with ORIN1001 alone:

        -Male or female with advanced solid tumors for which no effective standard of care
        treatments are available

        For dose escalation with ORIN1001 in combination with paclitaxel:

        -Males or females with relapsed refractory metastatic breast cancer (TNBC, MYC+, or ER+,
        HER2-) must have progressed through at least 2 lines of therapy and for whom there are no
        available therapies that confer a clinical benefit

        For dose expansion:

        a. Males or females with relapsed refractory metastatic breast cancer including:

        1. TNBC (i.e. estrogen receptor (ER)-, progesterone receptor-, and human epidermal growth
        factor receptor 2 [HER2]-) 2. ER+ HER2- breast cancer, and 3. MYC+ breast cancer for whom
        there are no available therapies that confer a clinical benefit Inclusion Criteria for Dose
        Escalation and Dose Expansion

          1. Adults aged ≥ 18 years

          2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          3. Life expectancy of 3-4 months

          4. Have at least one measurable lesion per RECIST 1.1

          5. Have adequate organ function, including all of the following:

               1. Adequate bone marrow reserve as defined by: ANC≥1.0 x 10 9/L; platelet count ≥75
                  x 10 9/L; hemoglobin ≥9 g/dL

               2. Hepatic: total bilirubin ≤2 x ULN, transaminases (AST/SGOT and/or ALT/SGPT) ≤ 3X
                  ULN;alkaline phosphatase ≤ 5 x ULN

               3. Renal: 24-hour creatinine clearance ≥ 30 mL/min calculated

          6. Adequate tissue sample from either archival tumor tissue or fresh biopsy of tumor at
             the screening for tumor genotyping.

          7. Male subjects must be surgically sterile or must agree to use physician approved
             contraception for 7 days prior to the first study drug administration to 30 days after
             the last dose of study treatment.

          8. Women of childbearing potential must have negative serum pregnancy test within 14 days
             prior the first administration of study drug and agree to use physician-approved
             contraception from 30 days prior to the first study drug administration to 30 days
             following the last study drug administration.

          9. Ability to understand and willingness to sign an informed consent prior to any study
             specific procedures.

         10. Resolution of all toxicities (except alopecia) from prior therapy to ≤ Grade 1 (CTCAE
             v5)

        Exclusion Criteria:

          1. Does not meet inclusion criteria

          2. Received any of the following within the specified time frame prior to the first
             administration of study drug:

             i. Excluding those with a history of coagulopathy ii. Excluding those who require
             concurrent use of anti-coagulants or anti-platelet medication, with exception of
             aspirin doses ≤ 81 mg/day, prophylaxis subcutaneous (SC) heparin or SC low-molecular
             weight heparin for deep vein thrombosis (DVT) prophylaxis or heparin flushes to
             maintain IV catherer patency iii. Excluding subjects that have Prothrombin time
             (PT)/international normalized ratio (INR) or activated partial thromboplastin time
             (aPTT) >1.5 x ULN b.Prior chemotherapy or other systemic anticancer therapy within 4
             weeks or 5 times the plasma half-life of the drug, whichever is shorter; c.Prior
             radiotherapy within 4 weeks; d.Major surgery within 2 weeks; e.Prior treatment with
             investigational drugs within 4 weeks; f. Myocardial infarction, uncontrolled
             angina,severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
             of acute ischemia, within 6 months prior to the fist dose of study drug

          3. Greater than Class II heart failure using New York Heart Association (NYHA) criteria

          4. The subject has uncontrolled human immunodeficiency virus (HIV) infection or active
             hepatitis B or C infection or other known active and/or uncontrolled infection

          5. Active autoimmune disease that is not appropriately controlled with treatment

          6. Active malignancy with the exception of:

               1. adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ
                  cervical cancer

               2. adequately treated stage I cancer from which the subject is currently in
                  remission, or

               3. any other cancer from which the subject has been disease-free for ≥3 years;

          7. Any serious uncontrolled medical or psychological disorder that would impair the
             ability to receive protocol therapy

          8. Any condition which places the subject at unacceptable risk or confounds the ability
             of the investigator to interpret study data

          9. The subject is pregnant or lactating woman. Any woman who becomes pregnant during the
             study will be withdrawn from the study.

         10. Known active uncontrolled or symptomatic brain metastases. Patients with a history of
             such mestastases that have been treated and are stable ≥28 days may be enrolled.
             Patients with no steroid use for at least 2 weeks prior to the time of enrollment are
             permitted.

         11. Failed to respond to the most recent dose of paclitaxel and must have been received at
             least 12 months prior to starting treatment.(combination arm only)

         12. Greater than Grade 1 neuropathy (combination arm only)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the safety of MTD/RP2D of single-agent daily ORIN1001 when administered orally in subjects with advanced solid tumors: NCI CTCAEv5 Common Toxicity Criteria
Time Frame:From first dose up to 21 days after last dose
Safety Issue:
Description:To determine the safety of the maximal tolerated dose/ recommendeded Phase 2 dose (MTD/RP2D). Incidence of the safety population will consist of all subjects who received a dose of study drug. Treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. Adverse events will be evaluated and recorded according to NCI CTCAEv5 Common Toxicity Criteria and will use medical terminology based on the Medical Dictionary for Regulatory Activities Terminology (MedDRA).

Secondary Outcome Measures

Measure:To evaluate the peak concentrations (Cmax) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the dose-dependent peak concentrations (Cmax) of ORIN1001 by direct inspection of the plasma concentration-time curves of ORIN1001 following single and repeat oral doses of ORIN 1001 as a single agent and in combination with paclitaxel.
Measure:To evaluate the time to peak concentrations (Tmax) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the dose-dependent time to peak concentrations (Tmax) of ORIN1001 by direct inspection of the plasma concentration-time curves of ORIN1001 following single and repeat oral doses of ORIN 1001 as a single agent and in combination with paclitaxel.
Measure:To evaluate the area under the plasma concentration versus time curve (AUC) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the dose-dependent area under the plasma concentration versus time curve (AUC) for ORIN1001 following single doses of ORIN 1001 as a single agent and in combination with paclitaxel.
Measure:To evaluate the last time point with a quantifiable concentration (AUClast) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the dose-dependent plasma levels of ORIN1001 from the time of dosing to the last time point with a quantifiable concentration (AUClast) of ORIN1001 following single doses of ORIN 1001 as a single agent and in combination with paclitaxel.
Measure:To evaluate the plasma concentration end of a dosing interval (Ctau) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the dose-dependent plasma concentrations (Cmax) of ORIN1001 as single agent or in combination with paclitaxel at the end of a dosing interval (Ctau), where tau is 24 hours for once daily dosing.
Measure:To evaluate the average plasma concentration (Cav) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the average plasma concentration (Cav) of ORIN1001 as single agent or in combination with paclitaxel during the dosing interval.
Measure:To evaluate the minimum plasma concentrations (Cmin) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the the minimum plasma concentrations (Cmin) reached by ORIN1001 as single agent or in combination with paclitaxel prior to administration of a second dose.
Measure:To evaluate the elimination constant (λz) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the dose-dependent plasma elimination constant (λz) for ORIN1001 as a single agent or in combination with paclitaxel.
Measure:To evaluate the terminal half-life (T1/2) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the dose-dependent terminal plasma half-life of ORIN1001 (T1/2) as a single agent or in combination with paclitaxel.
Measure:To evaluate the plasma clearance (CL/f) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the dose-dependent apparent total plasma clearance (CL/f) of ORIN1001 after oral administration as a single agent or in combination with paclitaxel.
Measure:To evaluate the volume of distribution (Vz/f) of ORIN1001 after oral administration as a single agent and in combination with paclitaxel.
Time Frame:2 months
Safety Issue:
Description:Determine the apparent volume of distribution (Vz/f) during terminal phase after oral administration of ORIN1001 as a single agent or in combination with paclitaxel.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Orinove, Inc.

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