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

NCT ID: NCT03950570

Last Updated: 2024-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

58 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-25

Study Completion Date

2023-01-30

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Advanced Solid Tumor Metastatic Breast Cancer

Keywords

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Solid tumors, Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

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)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1a: Dose Escalation with ORIN1001

In patients with advanced solid tumors or metastatic breast cancer: Treatment with a single oral agent, ORIN1001.

Group Type EXPERIMENTAL

ORIN1001

Intervention Type DRUG

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

Experimental Phase 1b: Dose escalation - ORIN1001 in combination with Abraxane dose

In patients with Relapsed, refractory metastatic breast cancer: Treatment with a combination of ORIN1001 and Abraxane.

Group Type EXPERIMENTAL

Abraxane

Intervention Type DRUG

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

ORIN1001

Intervention Type DRUG

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

Interventions

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Abraxane

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

Intervention Type DRUG

ORIN1001

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

Intervention Type DRUG

Eligibility Criteria

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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 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:

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


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)

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 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
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 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.
11. 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)
12. Greater than Grade 1 neuropathy (combination arm only)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Orinove, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mothaffar F Rimawi, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

UCLA Health Burbank Specialty Care

Burbank, California, United States

Site Status

UCLA Health Laguna Hills Cancer Care

Laguna Hills, California, United States

Site Status

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

Orange, California, United States

Site Status

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

Westwood, Los Angeles, California, United States

Site Status

University of Colorado Anschutz Medical Campus

Denver, Colorado, United States

Site Status

Highlands Ranch Hospital

Highlands Ranch, Colorado, United States

Site Status

University of Colorado Lone Tree Medical Center

Lone Tree, Colorado, United States

Site Status

University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Cancer Center of Kansas

Wichita, Kansas, United States

Site Status

St Lukes Cancer Institute

Kansas City, Missouri, United States

Site Status

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

Buffalo, New York, United States

Site Status

Northwell Health

New Hyde Park, New York, United States

Site Status

Northwell Heath Cancer Institute

New Hyde Park, New York, United States

Site Status

NYU Langone Health

New York, New York, United States

Site Status

Gabrail Cancer Center

Canton, Ohio, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Baylor College of Medicine Medical Center

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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ORIN1001-001

Identifier Type: -

Identifier Source: org_study_id