AzTrials
AzTrials

Advanced Solid TumorPhase 1/2NCT03950570

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

A Phase 1/2 study testing Abraxane and ORIN1001 in people with Advanced Solid Tumor and Metastatic Breast Cancer, run by Orinove, Inc. at 20 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
What is being tested?
Abraxane and ORIN1001
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
20 sitesUnited States
Study dates
25 May 2019to 30 Jan 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 Abraxane:
  • -Males or females with relapsed refractory metastatic breast cancer (TNBC 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:
  • Males or females with relapsed refractory metastatic breast cancer including:
Show all 21Show fewer
  • TNBC (i.e. estrogen receptor (ER)-, progesterone receptor-, and human epidermal growth factor receptor 2 [HER2]-)
  • ER+ HER2- breast cancer
  • Adults aged ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy of 3-4 months
  • Have at least one measurable lesion per RECIST 1.1
  • Have adequate organ function, including all of the following:
  • 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
  • Hepatic: total bilirubin ≤2 x ULN, transaminases (AST/SGOT and/or ALT/SGPT) ≤ 3X ULN;alkaline phosphatase ≤ 5 x ULN
  • Renal: 24-hour creatinine clearance ≥ 30 mL/min calculated
  • Adequate tissue sample from either archival tumor tissue or fresh biopsy of tumor at the screening for tumor genotyping.
  • 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.
  • 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.
  • Ability to understand and willingness to sign an informed consent prior to any study specific procedures.
  • Resolution of all toxicities (except alopecia) from prior therapy to ≤ Grade 1 (CTCAE v5)

Who cannot join

  • Does not meet inclusion criteria
  • Received any of the following within the specified time frame prior to the first administration of study drug:
  • 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 3 weeks or 5 times the plasma half-life of the drug, whichever is shorter; c.Prior radiotherapy within 2 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
  • Greater than Class II heart failure using New York Heart Association (NYHA) criteria
  • The subject has uncontrolled human immunodeficiency virus (HIV) infection or active hepatitis B or C infection or other known active and/or uncontrolled infection
  • Active autoimmune disease that is not appropriately controlled with treatment
Show all 16Show fewer
  • Active malignancy with the exception of:
  • adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
  • adequately treated stage I cancer from which the subject is currently in remission, or
  • any other cancer from which the subject has been disease-free for ≥3 years;
  • Any serious uncontrolled medical or psychological disorder that would impair the ability to receive protocol therapy
  • Any condition which places the subject at unacceptable risk or confounds the ability of the investigator to interpret study data
  • The subject is pregnant or lactating woman. Any woman who becomes pregnant during the study will be withdrawn from the study.
  • Known active uncontrolled or symptomatic brain metastases. Patients with a history of such metastases 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.
  • Failed to respond to the most recent dose of Abraxane and must have been received at least 12 months prior to starting treatment.(combination arm only)
  • Greater than Grade 1 neuropathy (combination arm only)

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

United States20 sites

  • Roswell Park Comprehensive Cancer Center (RPCCC) (Roswell Park Cancer Institute (RPCI))

    Buffalo, New York, 14203

  • UCLA Health Burbank Specialty Care

    Burbank, California, 91505

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • University of Colorado Anschutz Medical Campus

    Denver, Colorado, 80045

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • Highlands Ranch Hospital

    Highlands Ranch, Colorado, 80129

  • Baylor College of Medicine Medical Center

    Houston, Texas, 77030

  • St Lukes Cancer Institute

    Kansas City, Missouri, 64111

  • UCLA Health Laguna Hills Cancer Care

    Laguna Hills, California, 92653

  • University of Colorado Lone Tree Medical Center

    Lone Tree, Colorado, 80124

  • University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Northwell Health

    New Hyde Park, New York, 11042

  • Northwell Heath Cancer Institute

    New Hyde Park, New York, 11042

  • NYU Langone Health

    New York, New York, 10016

  • University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • University of Arizona Cancer Center

    Tucson, Arizona, 85719

  • University of California Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center (JCCC) - Oncology Center - Westwood

    Westwood, Los Angeles, California, 90024

  • Cancer Center of Kansas

    Wichita, Kansas, 67214

Other trials in United States

About this study

Official title: A Phase 1/2, Open Label, Dose-Escalation and Expansion Study of Oral ORIN1001 with and Without Chemotherapy in the Treatment of Subjects with Solid Tumors

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

Read the detailed description

This is a first in human, Phase 1/2, open label, dose escalation and dose expansion study that consists of two stages:

Phase 1: 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 Abraxane given intravenously in up to 18 subjects with relapsed refractory metastatic breast cancer (TNBC or ER+ HER2-).

Phase 2: An expansion stage of ORIN1001 alone (Cohort A: TNBC) and in combination with Abraxane (Cohort B: Myc+; Cohort C: ER+ HER2-, and Cohort D: TNBC) to estimate efficacy in up to 120 subjects with relapsed refractory metastatic breast cancer.

Being tested
Abraxane, ORIN1001
Keywords
Solid tumors, Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AbraxaneDrug

    In patients with relapsed. metastatic breast cancer, ORIN1001 will be administered in combination with Abraxane administered by intravenous infusion.

  • ORIN1001Drug

    ORIN1001 will be administered as a table as a monotherapy in the dose escalation phase in patients with advanced solid tumors or in combination with Abraxane in patients with relapse, refractory breast cancer

Study groups in NCT03950570
Study groupRoleWhat they receive
Phase 1a: Dose Escalation with ORIN1001ExperimentalIn patients with advanced solid tumors or metastatic breast cancer: Treatment with a single oral agent, ORIN1001.
Receives: Drug: ORIN1001
Experimental Phase 1b: Dose escalation - ORIN1001 in combination with Abraxane doseExperimentalIn patients with Relapsed, refractory metastatic breast cancer: Treatment with a combination of ORIN1001 and Abraxane.
Receives: Drug: Abraxane; Drug: ORIN1001

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    To determine the safety of the maximal tolerated dose/ recommended 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).

    Measured: From first dose up to 21 days after last dose

  2. To determine the safety MTD/RP2D of daily ORIN1001 when administered orally in combination with paclitaxel given intravenously at 175 mg/m2 once every three weeks in subjects with relapsed refractory metastatic breast cancer

    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).

    Measured: From first dose up to 21 days after last dose

  3. To evaluate the safety and tolerability of single-agent daily ORIN1001 when administered orally in the dose escalation and expansion stages of the study: NCI CTCAEv5 Common Toxicity Criteria

    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).

    Measured: From first dose up to 21 days after last dose

  4. To evaluate the safety and tolerability of daily ORIN1001 when administered orally in combination with Abraxane given intravenously at 100 mg/m2 once weekly for 3 weeks in the dose escalation and expansion stages of the study

    Incidence of number of participants with clinically significant change in vital signs. Vital signs include body weight, body temperature, resting blood pressure, pulse and respiratory rate.

    Measured: From first dose up to 28 days after last dose

Secondary outcomes (11)

  1. To evaluate the peak concentrations (Cmax) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.

    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 Abraxane.

    Measured: 2 months

  2. To evaluate the time to peak concentrations (Tmax) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.

    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 Abraxane.

    Measured: 2 months

  3. 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 Abraxane.

    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 Abraxane.

    Measured: 2 months

  4. To evaluate the last time point with a quantifiable concentration (AUClast) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.

    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 Abraxane.

    Measured: 2 months

  5. To evaluate the plasma concentration end of a dosing interval (Ctau) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.

    Determine the dose-dependent plasma concentrations (Cmax) of ORIN1001 as single agent or in combination with Abraxane at the end of a dosing interval (Ctau), where tau is 24 hours for once daily dosing.

    Measured: 2 months

  6. To evaluate the average plasma concentration (Cav) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.

    Determine the average plasma concentration (Cav) of ORIN1001 as single agent or in combination with Abraxane during the dosing interval.

    Measured: 2 months

  7. To evaluate the minimum plasma concentrations (Cmin) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.

    Determine the the minimum plasma concentrations (Cmin) reached by ORIN1001 as single agent or in combination with Abraxane prior to administration of a second dose.

    Measured: 2 months

  8. To evaluate the elimination constant (λz) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.

    Determine the dose-dependent plasma elimination constant (λz) for ORIN1001 as a single agent or in combination with Abraxane.

    Measured: 2 months

  9. To evaluate the terminal half-life (T1/2) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.

    Determine the dose-dependent terminal plasma half-life of ORIN1001 (T1/2) as a single agent or in combination with Abraxane.

    Measured: 2 months

  10. To evaluate the plasma clearance (CL/f) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.

    Determine the dose-dependent apparent total plasma clearance (CL/f) of ORIN1001 after oral administration as a single agent or in combination with Abraxane.

    Measured: 2 months

  11. To evaluate the volume of distribution (Vz/f) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.

    Determine the apparent volume of distribution (Vz/f) during terminal phase after oral administration of ORIN1001 as a single agent or in combination with Abraxane.

    Measured: 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2019
  2. Study start25 May 2019
  3. Primary completion30 Jan 2023
  4. Study completion30 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Phase 1: Dose escalation as a single agent (all tumor types); Dose escalation in combination with Abraxane (Breast Cancer); Phase 2: Dose expansion as a single agent or in combination with Abraxane (breast cancer)
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03950570
Sponsor's protocol ID
ORIN1001-001
Status last verified
Dec 2024
First submitted
23 Apr 2019
Last updated
31 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Abraxane and ORIN1001 in people with Advanced Solid Tumor and Metastatic Breast Cancer, run by Orinove, Inc. at 20 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03950570.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in