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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03950570
• Other study ID #: ORIN1001-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 25, 2019
• Est. completion date: December 30, 2024

Study information

• Verified date: November 2023
• Source: Orinove, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: December 30, 2024
• Est. primary completion date: January 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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 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)

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Abraxane
The doses of ORIN1001 in both dose escalation and dose expansion will be 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600mg, 800 mg, 1,000 mg, 1,200 mg Weekly paclitaxel will be 80 mg/m2 given intravenously for the dose escalation and dose expansion phases. cohorts as follows: 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, 1,000 mg, 1,300 mg and 1,500 mg administered for 21 days (one cycle).

Locations

Country	Name	City	State
United States	Roswell Park Comprehensive Cancer Center (RPCCC) (Roswell Park Cancer Institute (RPCI))	Buffalo	New York
United States	UCLA Health Burbank Specialty Care	Burbank	California
United States	Gabrail Cancer Center	Canton	Ohio
United States	University of Colorado Anschutz Medical Campus	Denver	Colorado
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Highlands Ranch Hospital	Highlands Ranch	Colorado
United States	Baylor College of Medicine Medical Center	Houston	Texas
United States	St Lukes Cancer Institute	Kansas City	Missouri
United States	UCLA Health Laguna Hills Cancer Care	Laguna Hills	California
United States	University of Colorado Lone Tree Medical Center	Lone Tree	Colorado
United States	University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Northwell Health	New Hyde Park	New York
United States	Northwell Heath Cancer Institute	New Hyde Park	New York
United States	NYU Langone Health	New York	New York
United States	University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center	Orange	California
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	University of California Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center (JCCC) - Oncology Center - Westwood	Westwood	California
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Orinove, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To quantify the objective response rate (ORR) of ORIN1001 alone and in combination with Abraxane	To quantify the proportion of patients with an objective tumor response as defined by RECIST 1.1 response criteria (SD, PR, CR).	Baseline up to approximately 2 years
Other	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	To quantify the proportion of patients with an objective tumor response as defined by RECIST 1.1 response criteria (SD, PR, CR).	Baseline up to approximately 2 years
Other	To measure the response duration in patients receiving ORIN1001 alone and in combination with Abraxane.	To measure the duration of response from the time point of first established response (SD, PR, CR) until the time of documented tumor progression.	Baseline up to approximately 2 years
Other	To quantify the difference in the duration of response in relapsed refractory metastatic breast cancer showing potentially response-predictive aberrations of MYC and other genes under ORIN1001 alone or in combination with Abraxane	To measure the duration of response from the time point of first established response (SD, PR, CR) until the time of documented tumor progression.	Baseline up to approximately 2 years
Other	To measure the time to response in patients receiving ORIN1001 alone and in combination with Abraxane.	To measure the time from cycle 1 day 1 dose to the time of first documentation of tumor response (SD, PR, CR).	Baseline up to approximately 2 years
Other	To quantify the difference in the time to response in relapsed refractory metastatic breast cancer showing potentially response-predictive aberrations of MYC and other genes under ORIN1001 alone or in combination with Abraxane.	To measure the time from cycle 1 day 1 dose to the time of first documentation of tumor response (SD, PR, CR).	Baseline up to approximately 2 years
Other	To measure the duration of progression free survival (PFS) in patients receiving ORIN1001 alone and in combination with Abraxane	To measure the time from cycle 1 day 1 dose administration to the time of documented disease progression or death from any cause.	Baseline up to approximately 2 years
Other	To quantify the difference in the progression free survival (PFS) in relapsed refractory metastatic breast cancer showing potentially response-predictive aberrations of MYC and other genes under ORIN1001 alone or in combination with Abraxane.	To measure the time from cycle 1 day 1 dose administration to the time of documented disease progression or death from any cause.	Baseline up to approximately 2 years
Other	To measure the duration of overall survival (OS) under treatment with ORIN1001 alone and in combination with Abraxane.	To measure the duration of overall survival (OS) which is the time from Cycle 1 day 1 until death from any cause.	Baseline up to approximately 2 years
Other	To quantify the difference in overall survival (OS) in relapsed refractory metastatic breast cancer showing potentially response-predictive aberrations of MYC and other genes under ORIN1001 alone or in combination with Abraxane	To measure the duration of Overall Survival (OS) which is the time from Cycle 1 day 1 until death from any cause.	Baseline up to approximately 2 years
Primary	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
Primary	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
Primary	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
Primary	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	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.	2 months
Secondary	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.	2 months
Secondary	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.	2 months
Secondary	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.	2 months
Secondary	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.	2 months
Secondary	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.	2 months
Secondary	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.	2 months
Secondary	To evaluate the elimination constant (?z) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the dose-dependent plasma elimination constant (?z) for ORIN1001 as a single agent or in combination with Abraxane.	2 months
Secondary	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.	2 months
Secondary	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.	2 months
Secondary	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.	2 months