Oral SM-88 in Patients With Metastatic HR+/HER2- Breast Cancer

NCT04720664 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY00003282
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 5

Brief Summary

This is a phase II single arm, open-label study of SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in metastatic HR+/HER2- breast cancer. It is designed to determine efficacy, defined as the objective response rate (ORR) of this investigational treatment. It is hypothesized that SM-88 used with MPS will lead to significant anti-tumor responses with acceptable toxicities in patients with metastatic HR+/HER2- breast cancer.

Conditions

Breast Cancer; Metastatic Breast Cancer; Hormone Receptor Positive Breast Carcinoma

Keywords

metastatic; hormone receptor-positive; HER2-negative; breast cancer; oral

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Anti-tumor efficacy will be defined as partial response (PR) or complete response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 for target lesions assessed by CT or MRI. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Every 8 weeks until progression (an average of 8 weeks)

Secondary Outcomes (4)

• Duration of Response (DOR)

  Every 8 weeks until Progression (an average of 8 weeks)

• Progression Free Survival (PFS)

  Every 8 weeks until progression (an average of 8 weeks)

• Clinical Benefit Rate (CBR) at ≥ 24 Weeks

  24 weeks

• Incidence of Treatment-Related Adverse Events [Safety and Tolerability]

  From the time of the administration of study drug until discontinuation of therapy (every 4 weeks on Day 1 of each cycle in a 28 day cycle; approximately 3 months)

Study Arms (1)

oral SM-88

EXPERIMENTAL

SM-88 taken with three conditioning agents: methoxsalen, phenytoin, and sirolimus

Drug: SM-88

Interventions

SM-88 DRUG

* SM-88, Two 230 mg capsules taken orally twice daily (920 mg daily). * Methoxsalen, One 10 mg capsule taken orally once daily. * Phenytoin, One 50 mg tablet taken orally once daily. * Sirolimus, One 0.5 mg tablet taken orally once daily.

oral SM-88

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced disease, not amenable to resection or radiation therapy with curative intent.
• Documentation of ER-positive and/or PR-positive tumor (≥1% positive stained cells) based on most recent tumor biopsy (discuss with the Principle Investigator if results in different biopsies are discordant in terms of hormone receptor positivity) utilizing an assay consistent with local standards.
• Documented HER2-negative tumor based on local testing on most recent tumor biopsy: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH) defined by current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines. Patients with equivocal HER2 in situ hybridization results according to current ASCO/CAP guidelines are eligible, as long as they have not received and are not scheduled to receive anti-HER2 treatment.
• Must have progressed on at least 2 lines of endocrine therapy in either the adjuvant or metastatic setting and progressed on a CDK4/6 inhibitor.
• Must have received no more than 4 lines of systemic therapy (for example, including but not limited to endocrine therapy, targeted therapy, biologic therapy, chemotherapy, or experimental therapy) for the treatment of breast cancer in the metastatic setting.
• Premenopausal or postmenopausal female or male patients 18 years of age or older.
• Measurable disease as defined by RECIST v1.1 criteria (tumor ≥ 1 cm in longest diameter on axial image on computed tomography (CT) or magnetic resonance imaging (MRI) and/or lymph node(s) ≥ 1.5 cm in short axis on CT or MRI) on baseline imaging. Bone only metastases must have associated \> 10 mm soft tissue mass.
• Asymptomatic brain metastases are allowed if the lesions are not considered to need local therapy. Previously treated brain metastases are allowed as long as they are \> 4 weeks from local therapy, clinically asymptomatic, and not requiring high-dose corticosteroids. Patients may remain on steroids for CNS disease if they are taking a stable dose that is less than 10mg of prednisone per day, or the equivalent.
• Must be capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by the IRB, prior to the initiation of any screening or study-specific procedures.
• Life expectancy of more than 3 months.
• ECOG performance status 0-1
• Pregnancy must be ruled out in women of childbearing potential. Serum or urine pregnancy test must be negative within 14 days of treatment start in women of childbearing potential and must be willing to have pregnancy test approximately every 4 weeks. Pregnancy testing does not need to be pursued in patients who are judged to be postmenopausal before enrollment, or who have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation. Patients may be considered postmenopausal in the case that one of the following criteria applies,
• Prior bilateral oophorectomy, OR
• Age ≥ 60 years, OR
• Age \< 60 years with intact uterus and amenorrhoeic for ≥ 12 consecutive months prior to chemotherapy and/or endocrine therapy exposure

You may not qualify if:

• Concurrent therapy with other approved or investigational cancer treatment agents, except bisphosphonates and RANKL inhibitors.
• Bone-only metastases without soft tissue masses measuring \> 10 mm.
• Inability to comply with study requirements.
• Diagnosis of other invasive cancer except for adequately treated cervix cancer, or more than 5 years since other diagnosis of invasive cancer (including invasive squamous cell cancers due to contraindication for methoxsalen use) without current evidence of disease.
• Pregnant women or women of childbearing potential without a negative pregnancy test (serum or urine) within 14 days prior to starting study treatment.
• Breastfeeding must be discontinued prior to study entry.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea/vomiting, chronic diarrhea, malabsorption syndrome, intestinal obstruction, or small bowel resection)
• Patients with clinically significant liver disease, including active viral (including hepatitis B, hepatitis C, etc) or other known active hepatitis, current alcohol abuse, or cirrhosis.
• Known chronic hepatitis B virus infection (testing not required prior to enrollment).
• Uncontrolled HIV infection defined as any of the following 3 criteria: CD4 counts ≤ 350 cells/μL; serum HIV viral load ≥ 400 copies/mL; on a antiretroviral regimen for \< 4 weeks prior to treatment with study drugs if anti-retroviral therapy is deemed necessary or appropriate by the investigator.
• Previous enrollment in this study or any other study investigating SM-88.
• History of any known drug allergies to any study medication.
• Clinically significant and uncontrolled major medical condition(s) including, but not limited to uncontrolled nausea/vomiting/diarrhea; active, uncontrolled infection; symptomatic congestive heart failure (New York Heart Association \[NYHA\] class ≥ II); unstable angina pectoris; cardiac arrhythmia requiring hospitalization in the past 3 months; stroke or MI in the past 6 months.
• Psychiatric illness or social situation that would limit compliance with study requirements.
• Active uncontrolled or symptomatic brain metastases. Previously treated and clinically stable brain metastases, as per Investigator's judgement, are permitted.

Sponsors & Collaborators

• Georgetown University: lead
• Tyme, Inc: collaborator

Study Sites (5)

MedStar Georgetown University Hospital, Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

MedStar Franklin Square Medical Center

Baltimore, Maryland, 21237, United States

Location

MedStar Good Samaritan Hospital

Baltimore, Maryland, 21239, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

racemetyrosine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Nadia Ashai, MD
• Organization: Georgetown University

nadia.ashai@medstar.net

202-444-2223

Study Officials

• Nadia Ashai, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: January 22, 2021
• Study Start: September 22, 2021
• Primary Completion: February 10, 2023
• Study Completion: February 10, 2023
• Last Updated: August 28, 2023
• Results First Posted: August 28, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)