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Pancreatic CancerPhase 2/3NCT03512756

A Randomized Phase 2/3 Multi-Center Study of SM-88 in Participants With Metastatic Pancreatic Cancer

A Phase 2/3 study testing SM-88 used with MPS (methoxsalen, phenytoin, sirolimus) and Capecitabine, Gemcitabine, and 5-FU in people with Pancreatic Cancer, run by Tyme, Inc at 20 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

A prospective, open-label phase 2/3 trial in metastatic pancreatic cancer participants who have failed two lines of prior systemic therapy. The trial is designed to evaluate the safety and efficacy of SM-88 used with MPS (methoxsalen, phenytoin and sirolimus) in pancreatic cancer and will measure multiple endpoints… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Cancer
What is being tested?
SM-88 used with MPS (methoxsalen, phenytoin, sirolimus) and Capecitabine, Gemcitabine, and 5-FU
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
130 participants
Where
20 sitesUnited States
Study dates
27 Mar 2018to 28 Dec 2021
Phase
Phase 2/3
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

  • 1.
  • Part 1
  • Biopsy-proven metastatic pancreatic adenocarcinoma with documented radiographic disease progression on or after one or more systemic therapies. Chemotherapy given as part of prior chemoradiation in the setting of non-metastatic pancreatic cancer does not count as a line of therapy. Chemotherapy given for at least 4 months as adjuvant after complete response is considered as a first line therapy.
  • Part 2
  • Biopsy-proven metastatic pancreatic adenocarcinoma on or after two prior lines of systemic therapy. Chemotherapy given as part of prior chemo- radiation in the setting of non-metastatic pancreatic cancer does not count as a line of therapy unless metastases develop within 6 months of completing the chemo sensitization. Chemotherapy given for at least 4 months as adjuvant after a CR to any therapy (e.g. surgery and radiation therapy) is also considered as a first line therapy. Of the two prior lines, participants should have received a gemcitabine-based regimen for a prior line and a 5-FU based regimen as a prior line of therapy. Investigational therapies as part of a prior line regimen are permitted.
  • 2. Participants Have received two (2) and not more than two (2) previous systemic regimens for the treatment of pancreatic adenocarcinoma
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  • 3. Must be eligible to receive one or more of the Physician Choice options.
  • 4. Radiographically measurable disease of at least one site by CT scan (or MRI, if allergic to CT contrast media). Imaging results must be obtained within the 14-day window prior to randomization
  • 5. Must have completed any investigational cancer therapy at least 30 days prior to first dose.
  • 6. Must have completed any other cancer therapy at least 14 days prior to first dose and recovered from major side effects of prior therapies or procedures.
  • 7. ≥18 years of age.
  • 8. ECOG PS ≤2.
  • 9. Adequate organ function defined as follows (lab results must be obtained within the 7-day window prior to randomization):
  • All laboratory parameters ≤ Grade 2 NCI Common Terminology Criteria for Adverse Events (CTCAE) criteria.
  • In addition:
  • Hematologic: Platelets ≥ 100 x 109 g/dL; Absolute Neutrophil Count ≥ 1.5 x 109/L (without platelet transfusion or growth factors within the 7 days prior to the screening laboratory assessment).
  • Hepatic: transaminase /alanine transaminase ≤ 2.5 x upper limit of normal (ULN); total or conjugated bilirubin ≤ 1.5 x ULN, alkaline phosphatase (ALP) < 2.5 x ULN.
  • Renal: serum creatinine ≤1.5 x ULN and creatinine clearance ≥ 60 mL/min as calculated by the Cockroft-Gault method.
  • Coagulation: International normalized ratio (INR) ≤ 1.2 within 28 days of starting study.
  • Albumin: ≥ 3.0 g/dL. vi. Weight: No more than a 5% change from Screening to Randomization (must be at least 1 week apart).
  • 10. All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before baseline, with the exception of alopecia and neurotoxicity (CTCAE Grade 1 or 2 permitted).
  • 11. Able and willing to provide written informed consent to participate in this study.
  • 12.Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • 13. Must be able to swallow whole capsules.
  • 14. Females must either be of non-reproductive potential, not breast-feeding or must have a negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on Day 1.
  • 15. Participant of fertile potential who engage in heterosexual intercourse with partners of childbearing potential must attest to the use of highly effective contraception while enrolled in the study and for at least 6 months following the last dose of study drug.
  • Highly effective birth control methods include the following (the participantshould choose 2 to be used with their partner):
  • Oral, injectable, or implanted hormonal contraceptives.
  • Condom with a spermicidal foam, gel, film, cream, or suppository.
  • Occlusive cap (diaphragm or cervical/vault cap) with a spermicidal foam, gel, film, cream, or suppository.
  • Or any one of the following:
  • Intrauterine device.
  • Intrauterine system (for example, progestin-releasing coil).
  • Vasectomized male (as determined by the investigator).
  • Tubal ligation/sterilization (female).

Who cannot join

  • Any screening laboratory, ECG, or other findings that, in the opinion of the investigator, medical monitor or the sponsor, indicate an unacceptable risk for the participant's participation in the study.
  • History or evidence of any clinically significant disorder, condition, or disease that, in the opinion of the investigator or medical monitor would pose a risk to the participant's safety or interfere with the study evaluations, procedures, or completion. Examples include intercurrent illness such as active uncontrolled infection, active or chronic bleeding event within 28 days of baseline, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
  • History of a concurrent or second malignancy, except for adequately treated localized basal cell or squamous cell carcinoma of the skin, adequately treated superficial bladder cancer, adequately treated Stage 1 or 2 cancer currently in complete remission; or any other cancer that has been in complete remission for ≥ 5 years.
  • Participants with MSI-H pancreatic cancer who have not previously received pembrolizumab.
  • Any known actionable mutation (e.g. BRCA mutation) who have not been treated with an approved drug for the mutation (the drug does not have to be approved for the indication).
  • Radiation to all target lesions within 12 weeks of study baseline.
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  • No measurable target lesions.
  • Current use, or up to 14 days prior use, of a restricted medication (see Section 8.7) or requires any of these medications during treatment phase.
  • Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e. larger than that required for placement of central venous access, percutaneous feeding tube, or biopsy) within 28 days of the first dose of study drug.
  • Minor surgical procedures within 7 days of baseline, or not yet recovered from any prior surgery.
  • Any dysphagia, odynophagia, esophageal dysmotility or stricture, known gastrointestinal (GI) malabsorption syndrome, or intractable diarrhea that may significantly alter the absorption of any of the components of SM-88 used with MPS, e.g., cirrhosis.
  • Known human immunodeficiency (HIV) virus infection. Note: HIV testing is not required in the absence of clinical suspicion.
  • Known hepatitis B surface antigen (HBsAg) positive.
  • Known hepatitis C (HCV) viral RNA present.
  • Have previously been enrolled in this study or any other study investigating SM-88 or who have previously received any SM-88, methoxsalen, phenytoin, or sirolimus in a clinical trial.
  • History of any known drug allergies to any study medication.
  • Are currently enrolled in, or have discontinued within 14 days of screening, from a clinical trial involving an investigational product or non-approved use of a drug or device.
  • Must not have any 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 or cardiac arrhythmia; psychiatric illness/social situation that would limit compliance with study requirements.
  • >5% weight loss over the 28 days prior to consent or >5% change in weight from consent to randomization.
  • Participants that have a variety of factors influencing oral drugs (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc.).
  • Central nervous system metastasis; with the exception of participants who have stable brain metastases as defined as off steroids and no CNS progress for 6 months after CNS treatment.
  • Pregnant or lactating women.
  • Substance abuse that cannot be ended, or participants with mental disorders that will prevent compliance or evaluation including uncontrolled schizophrenia, uncontrolled depression or other uncontrolled disorders.
  • History of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins; or a history of prior acute hepatotoxicity attributable to phenytoin.
  • Participants exhibiting idiosyncratic reactions to psoralen compounds.
  • Participants with a hypersensitivity to sirolimus.
  • Participants 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.
  • Participants 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).
  • Participants with cutaneous melanoma or invasive squamous cell carcinomas or a history thereof, except for those in complete remission for ≥5 years (due to contraindication for use of methoxsalen).
  • Participants with prior 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).
  • Participants 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.
  • Participants 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]).
  • Participants with interstitial lung disease (ILD) [including pneumonitis, bronchiolitis obliterans organizing pneumonia (BOOP), and pulmonary fibrosis].
  • Baseline repeated prolongation of QT/QTc interval [e.g. > 480 milliseconds (ms)] (CTCAE Grade 1) using Fredericia's QT correction formula.
  • A family history of Long QT Syndrome or Torsades de Pointes
  • Clinically significant cataracts or aphakia.
  • Presence of ascites or pleural effusion.

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

United States20 sites

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • The Ohio State University

    Columbus, Ohio, 43221

  • Texas Oncology-Baylor

    Dallas, Texas, 75246

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City Of Hope

    Duarte, California, 91010

  • North Shore Hematology Oncology

    East Setauket, New York, 11733

  • NY Cancer and Blood Specialist

    East Setauket, New York, 11733

  • MD Anderson

    Houston, Texas, 77030

  • Hartford Healthcare Cancer

    New Britain, Connecticut, 06053

  • University Medical Center

    New Orleans, Louisiana, 70112

  • NYU Langone Health

    New York, New York, 10016

  • Central Park Hematology & Oncology

    New York, New York, 10028

  • Weill Cornell

    New York, New York, 10065

  • Sarcoma Oncology Research Center

    Santa Monica, California, 90403

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • June E. Nylen Cancer Center

    Sioux City, Iowa, 51101

  • Washington University

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

  • Advent Health Florida Hospital Tampa

    Tampa, Florida, 33613

  • New York Cancer and Blood Specialist

    The Bronx, New York, 10469

Other trials in United States

About this study

Official title: A Randomized Phase 2/3 Multi-Center Study of SM-88 in Subjects With Pancreatic Cancer Whose Disease Has Progressed or Recurred

A prospective, open-label phase 2/3 trial in metastatic pancreatic cancer participants who have failed two lines of prior systemic therapy. The trial is designed to evaluate the safety and efficacy of SM-88 used with MPS (methoxsalen, phenytoin and sirolimus) in pancreatic cancer and will measure multiple endpoints, including overall survival, progression free survival, relevant biomarkers, quality of life, safety, and overall response rate.

(Part 1 enrollment complete) In the initial stage of the trial (36 participants), two dose levels of SM-88's metyrosine-derivative was evaluated.

(Part 2 actively enrolling) The second part will consist of a subsequent expansion of the trial to further assess safety and efficacy of SM-88 used with MPS containing the selected SM-88 RP2D from Part 1. A total of 250 participants in the second part will be randomized 1:1 either to the SM-88 arm (125 participants) or Physician's Choice of therapy for the Control Arm (125 participants). Participants should have previously received two lines of prior systemic therapy.

Read the detailed description

Please refer to Inclusion/Exclusion Criteria and Summary

Being tested
SM-88 used with MPS (methoxsalen, phenytoin, sirolimus), Capecitabine, Gemcitabine, and 5-FU
Keywords
Pancreatic cancer, Pancreas cancer, Pancreatic, Pancreas, cancer, low toxicity, chemotherapy, metastatic, SM-88, SM88, 3rd line, third line, CMBT, well tolerated, MPS, Racemetyrosine, Methoxsalen, Sirolimus, Phenytoin
Medical subject headings
Pancreatic Neoplasms, Neoplasms, Neoplasm Metastasis

What participants receive

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

  • SM-88 used with MPS (methoxsalen, phenytoin, sirolimus)Drug

    Also called SM-88, Racemetyrosine

    Daily oral therapy for cancer

  • Capecitabine, Gemcitabine, and 5-FUDrug

    Also called Physician's Choice

    Investigator choice of the following therapies:

    Capecitabine, Gemcitabine, and 5-FU

Study groups in NCT03512756
Study groupRoleWhat they receive
Part 1 and Part 2 SM-88 ArmExperimental(Part 1 enrollment complete) SM-88 used with MPS (methoxsalen, phenytoin and sirolimus) (Part 2 actively enrolling) SM-88 (920 mg per day) used with MPS (methoxsalen, phenytoin and sirolimus) will be administered to 125 evaluable participants until unacceptable toxicity, disease progression, or any of the treatment discontinuation criteria are met.
Receives: Drug: SM-88 used with MPS (methoxsalen, phenytoin, sirolimus)
Physician's ChoiceExperimentalPhysician's Choice therapy will be administered for a total of 125 evaluable participants until unacceptable toxicity, disease progression, or any of the treatment discontinuation criteria are met.
Receives: Drug: Capecitabine, Gemcitabine, and 5-FU

What is being measured

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

  1. Overall Survival (OS)

    OS was defined as the number of days between the first study drug administration and death from any cause. Results are reported in weeks.

    Measured: Up to 12 months

Secondary outcomes (1)

  1. Progression Free Survival (PFS)

    Progression-Free Survival (PFS), is defined as the time from randomization to first documentation of objective tumor progression (progressive disease) or death due to any reasons whichever comes first. Disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Results are reported in weeks.

    Measured: Up to 12 months

Timeline

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

  1. First posted1 May 2018
  2. Study start27 Mar 2018
  3. Primary completion28 Dec 2021
  4. Study completion28 Dec 2021

Why it stopped: Sponsor's decision

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
130 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03512756
Sponsor's protocol ID
Tyme-88-Panc
Status last verified
Oct 2024
First submitted
18 Apr 2018
Last updated
6 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Noel MS, Kim S, Hartley ML, Wong S, Picozzi VJ, Staszewski H, Kim DW, Van Tornout JM, Philip PA, Chung V, Ocean AJ, Wang-Gillam A. A randomized phase II study of SM-88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond. Cancer Med. 2022 Nov;11(22):4169-4181. doi: 10.1002/cam4.4768. Epub 2022 May 2.

    PubMed 35499204

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing SM-88 used with MPS (methoxsalen, phenytoin, sirolimus) and Capecitabine, Gemcitabine, and 5-FU in people with Pancreatic Cancer, run by Tyme, Inc at 20 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 35 inclusion and 37 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 6 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 6 Nov 2024). 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?

Overall Survival (OS) (time frame: Up to 12 months). 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 NCT03512756, which also lists 1 linked publication.

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 6 Nov 2024.

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