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Breast CancerPhase 2OASISNCT04720664

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

A Phase 2 study testing SM-88 in people with Breast Cancer and Metastatic Breast Cancer, run by Georgetown University at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
SM-88
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
5 sitesUnited States
Study dates
22 Sep 2021to 10 Feb 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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.
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  • 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
  • Willingness to utilize adequate contraception if of childbearing potential. Women of childbearing potential must use adequate contraception for the duration of protocol treatment and for at least 6 months after the last treatment with SM-88 used with MPS. Adequate contraception is defined as one highly effective form (i.e., abstinence, (fe)male sterilization) OR two effective forms (IUD [non-hormonal preferred], condom with spermicidal foam / gel / film / cream / suppository, occlusive cap with spermicidal foam / gel / film / cream / suppository).
  • Must be able and willing to swallow pills whole and retain oral medication.
  • Adequate hematologic parameters (Patients must be able to meet the following criteria without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample):
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3; Patients must be able to meet the criteria without receipt of colony stimulating factors within 2 weeks before obtaining sample
  • Platelets ≥ 100,000/mm3; Patients must be able to meet the criteria without receipt of transfusion within 2 weeks before obtaining sample
  • Hemoglobin ≥ 9 g/dL; Patients must be able to meet the criteria without receipt of transfusion within 2 weeks before obtaining sample
  • Serum creatinine clearance ≥ 60 mL/min based on Cockcroft-Gault equation
  • Adequate hepatic parameters:
  • Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) ≤ 3 x ULN (upper limit of normal)
  • Total serum bilirubin ≤ 1.5 x ULN, except for patients with a documented history of Gilbert's Syndrome who can be enrolled at PI discretion
  • For patients with liver metastases, AST and ALT < 5x the institution's ULN and/or total bilirubin ≤ 3.0x the institution's ULN are acceptable as long as there is no persistent nausea, vomiting, right upper quadrant pain or tenderness, fever, or rash.
  • Alkaline phosphatase ≤2.5 x ULN (≤5.0 x ULN if bone metastases present)
  • Resolution of all acute toxic effects of prior therapy, including radiotherapy to grade ≤1 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures.
  • Must have discontinued all previous therapies for cancer (including endocrine therapy, CDK4/6 inhibitor therapy, cytotoxic chemotherapy, targeted therapy [including, but not limited to, everolimus], radiotherapy, immunotherapy, and investigational therapy) for at least 14 days prior to receiving study drugs and recovered from the acute effects of therapy (treatment-related toxicity resolved to baseline) except for residual alopecia or peripheral neuropathy.

Who cannot join

  • 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.
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  • 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).
  • Patients with chronic hepatitis C virus infection may be enrolled if there is no clinical/laboratory evidence of cirrhosis per investigator AND the patient's liver function tests fall within the parameters set in the inclusion criteria.
  • 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.
  • Patients with a seizure disorder that is not well controlled or who have required a change in seizure medications within 60 days of enrollment to the trial.
  • Patients with a history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins; or a history of prior acute hepatotoxicity attributable to phenytoin.
  • Patients treated, or anticipated to be treated, with delavirdine (due to potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors caused by phenytoin).
  • Patients exhibiting idiosyncratic reactions to psoralen compounds.
  • Patients with a history of the light sensitive diseases for which methoxsalen would be contraindicated. Diseases associated with photosensitivity include lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum, and albinism.
  • Patients with cutaneous melanoma or invasive squamous cell carcinomas or a history thereof, except for those with stage 1A melanoma or in complete remission for ≥5 years (due to contraindication for use of methoxsalen).
  • Patients with a hypersensitivity to sirolimus. Sirolimus does cause immune suppression at the prescribed doses and physicians should note the drugs black box warning to exclude any patient they believe the other exclusion criteria does not reflect.
  • Patients with prior allogenic bone marrow transplant or solid organ transplant organ transplant or being treated, or anticipated to be treated, with cyclosporine (because long-term administration of the combination of cyclosporine and sirolimus is associated with deterioration of renal function).
  • Patients treated, or anticipated to be treated, with a calcineurin inhibitor (because concomitant use of sirolimus and a calcineurin inhibitor increases the risk of calcineurin inhibitor-induced hemolytic uremic syndrome/thrombotic thrombocytopenic purpura/thrombotic microangiopathy [HUS/TTP/TMA]).
  • Current use of known strong inhibitors or inducers of CYP3A4, CYP2C9 or CYP2C19 within 14 days of initiation of study drug. When possible these medications and grapefruit juice should be avoided for the duration of the study treatment and alternate therapies are preferred.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • MedStar Franklin Square Medical Center

    Baltimore, Maryland, 21237

  • MedStar Good Samaritan Hospital

    Baltimore, Maryland, 21239

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • MedStar Georgetown University Hospital, Lombardi Comprehensive Cancer Center

    Washington D.C., District of Columbia, 20007

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: OASIS: Phase II Trial of OrAl SM-88 in Patients With Metastatic Hormone Receptor-posItive HER2-negative (HR+/HER2-) breaSt Cancer

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.

Read the detailed description

This is a multicenter phase II single arm trial designed to evaluate the efficacy of SM-88 plus three subtherapeutic conditioning agents (methoxsalen, phenytoin, and sirolimus [MPS]) in patients with metastatic HR+/HER2- breast cancer. .

Thirty patients will be enrolled in first stage of the study, and if 3 or more patients have an objective response (complete or partial response) then an additional 20 patients will be enrolled in the second stage of the study. Patients will receive the recommended phase 2 dose (RP2D) of SM-88 (460 mg by mouth [PO] twice a day [BID] D1 - 28) as well as three conditioning agents (MPS): methoxsalen (10 mg PO daily [Qd] D1 - 28), phenytoin (50 mg PO Qd D1 - 28), and sirolimus (0.5 mg PO Qd D1 - 28).

Assessment of efficacy will be conducted every 3 cycles (approximately every 12 weeks) with CT chest/abdomen/pelvis using RECIST v1.1 criteria. Safety including clinic visits, and exams will occur every 4 weeks on Day 1 of each cycle. Laboratory testing will be performed every 2 weeks for the first 2 cycles and then on Day 1 of each subsequent cycle.

Being tested
SM-88
Keywords
metastatic, hormone receptor-positive, HER2-negative, breast cancer, oral
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

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

  • SM-88Drug

    • 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.
Study groups in NCT04720664
Study groupRoleWhat they receive
oral SM-88ExperimentalSM-88 taken with three conditioning agents: methoxsalen, phenytoin, and sirolimus
Receives: Drug: SM-88

What is being measured

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

  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.

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

Secondary outcomes (4)

  1. Duration of Response (DOR)

    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. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

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

  2. Progression Free Survival (PFS)

    Defined as the time in days from study entry to the first documented disease progression per RECIST v1.1 as assessed by local site or death. Patients who are alive and free from progression on the date of closing follow-up will be censored on that date.

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

  3. Clinical Benefit Rate (CBR) at ≥ 24 Weeks

    The percentage of patients who have complete response (CR), partial response (PR), or stable disease (SD) at ≥ 24 weeks will be reported.

    Measured: 24 weeks

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

    The number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Measured: 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)

Timeline

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

  1. First posted22 Jan 2021
  2. Study start22 Sep 2021
  3. Primary completion10 Feb 2023
  4. Study completion10 Feb 2023

Why it stopped: Lack of efficacy

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04720664
Sponsor's protocol ID
STUDY00003282
Acronym
OASIS
Status last verified
Mar 2023
First submitted
14 Dec 2020
Last updated
28 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SM-88 in people with Breast Cancer and Metastatic Breast Cancer, run by Georgetown University at 5 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 29 inclusion and 26 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: stopped early, as of the sponsor's last update on 28 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 phase mean?

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?

Yes. Results are posted in the registry (first posted 28 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate (ORR) (time frame: Every 8 weeks until progression (an average of 8 weeks)). 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 NCT04720664.

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 28 Aug 2023.

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