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

NCT03950570 | Completed Phase 1 FDA Drug

• 1 other identifier: ORIN1001-001
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 20

Brief 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).

Conditions

Advanced Solid Tumor; Metastatic Breast Cancer

Keywords

Solid tumors, Breast Cancer

Outcome Measures

Primary Outcomes (4)

• 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).

  From first dose up to 21 days after last dose

• 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).

  From first dose up to 21 days after last dose

• 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).

  From first dose up to 21 days after last dose

• 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.

  From first dose up to 28 days after last dose

Secondary Outcomes (11)

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

  2 months

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

  2 months

• 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.

  2 months

• 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.

  2 months

• 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.

  2 months

Other Outcomes (10)

• To quantify the objective response rate (ORR) of ORIN1001 alone and in combination with Abraxane

  Baseline up to approximately 2 years

• To quantify the difference in the objective response rate (ORR) in relapsed refractory metastatic breast cancer showing potentially response-predictive aberrations of MYC and other genes under ORIN1001 alone or in combination with Abraxane

  Baseline up to approximately 2 years

• To measure the response duration in patients receiving ORIN1001 alone and in combination with Abraxane.

  Baseline up to approximately 2 years

Study Arms (2)

Phase 1a: Dose Escalation with ORIN1001

EXPERIMENTAL

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

Drug: ORIN1001

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

EXPERIMENTAL

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

Drug: Abraxane; Drug: ORIN1001

Interventions

Abraxane DRUG

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

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

ORIN1001 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; Phase 1a: Dose Escalation with ORIN1001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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
• 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
• 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)

Sponsors & Collaborators

• Orinove, Inc.: lead

Study Sites (20)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

UCLA Health Burbank Specialty Care

Burbank, California, 91505, United States

Location

UCLA Health Laguna Hills Cancer Care

Laguna Hills, California, 92653, United States

Location

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

Orange, California, 92868, United States

Location

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

Westwood, Los Angeles, California, 90024, United States

Location

University of Colorado Anschutz Medical Campus

Denver, Colorado, 80045, United States

Location

Highlands Ranch Hospital

Highlands Ranch, Colorado, 80129, United States

Location

University of Colorado Lone Tree Medical Center

Lone Tree, Colorado, 80124, United States

Location

University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

St Lukes Cancer Institute

Kansas City, Missouri, 64111, United States

Location

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

Buffalo, New York, 14203, United States

Location

Northwell Health

New Hyde Park, New York, 11042, United States

Location

Northwell Heath Cancer Institute

New Hyde Park, New York, 11042, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Baylor College of Medicine Medical Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Mothaffar F Rimawi, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: May 15, 2019
• Study Start: May 25, 2019
• Primary Completion: January 30, 2023
• Study Completion: January 30, 2023
• Last Updated: December 31, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)