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A Multi-Center Study of SM-88 in Subjects With Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03512756
Recruitment Status : Recruiting
First Posted : May 1, 2018
Last Update Posted : November 21, 2018
Information provided by (Responsible Party):
Tyme, Inc

Brief Summary:
A prospective, open-label phase 2 trial in metastatic pancreatic cancer subjects who have failed at least one line of any prior chemotherapy. The trial is designed to evaluate the of SM-88 therapy on pancreatic cancer and will measure multiple efficacy and safety endpoints, including overall response rate, overall survival, progression free survival, relevant biomarkers, quality of life and safety. In the initial stage of the trial (36 subjects), two dose levels of SM-88's metyrosine-derivative will be evaluated.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: Combination of metyrosine-derivative with low-dose sirolimus, phenytoin and methoxsalen Phase 2

Detailed Description:
Both investigator determined and independent blinded central review will be used for determining outcomes.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 115 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single (Outcomes Assessor)
Masking Description: Blinded independent centralized radiologic review and un-masked investigator determined outcomes are used in this trial.
Primary Purpose: Treatment
Official Title: A Phase II Multi-Center Study of SM-88 in Subjects With Pancreatic Cancer Whose Disease Has Progressed or Recurred After/on First Line Chemotherapy
Actual Study Start Date : March 27, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Lower dose metyrosine-derivative
Combination of lower dose metyrosine-derivative, low-dose sirolimus, phenytoin and methoxsalen
Drug: Combination of metyrosine-derivative with low-dose sirolimus, phenytoin and methoxsalen
Daily oral combination therapy for cancer
Other Name: SM-88

Experimental: Higher dose metyrosine-derivative
Combination of higher dose metyrosine-derivative, low-dose sirolimus, phenytoin and methoxsalen
Drug: Combination of metyrosine-derivative with low-dose sirolimus, phenytoin and methoxsalen
Daily oral combination therapy for cancer
Other Name: SM-88

Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: From date of randomization until the date of first documented progression or date of death, whichever came first, assessed up to 60 months ]
    Overall response rate (complete response + partial response) by central review of modified RECIST 1.1 using blinded independent central review (BICR) of radiological scans.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  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.
  2. Subjects must be unwilling or unable to tolerate other non-study systemic chemotherapy.
  3. Subjects must have measurable lesions (according to standard RECIST 1.1).
  4. Subjects must have completed systemic therapy at least 28 days prior to first dose.
  5. Subjects must have recovered from major side effects of prior therapies or procedures.
  6. ≥18 years of age.
  7. ECOG performance status ≤2.
  8. Life expectancy >3 months, in the judgment of the investigator.
  9. Adequate organ function defined as follows:

    1. Hematologic: Platelets ≥100 x 10(9)/L; ANC ≥1.5 x 10(9)/L (without platelet transfusion or growth factors within the 7 days prior to the screening laboratory assessment)
    2. Hepatic: aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN); total or conjugated bilirubin ≤1.5 x ULN
    3. Renal: serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥60 mL/min as calculated by the Cockroft-Gault method
  10. Coagulation: International normalized ratio (INR) ≤1.2 within 28 days of starting study.
  11. 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).
  12. Able and willing to provide written informed consent to participate in this study.
  13. Subject is 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.
  14. Subjects must be able to swallow whole capsule.
  15. Female subjects 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.
  16. Subjects of fertile potential who engage in heterosexual intercourse with partners of childbearing potential must agree to use highly effective contraception while enrolled in the study and for at least 6 months following the last dose of study drug

Exclusion Criteria:

  1. Any screening laboratory, electrocardiogram (ECG), or other findings that, in the opinion of the investigator or the sponsor, indicate an unacceptable risk for the subject's participation in the study.
  2. 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 subject'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.
  3. History of a concurrent or second malignancy, except for adequately treated local 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.
  4. Subjects with MSI-H pancreatic cancer who have not previously received pembrolizumab.
  5. Radiation to all target lesions within 12 weeks of study baseline,
  6. No measurable target lesions.
  7. Current use, or up to 14 days prior use, of certain prohibited medication or requires any of these medications during treatment phase.
  8. 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
  9. Minor surgical procedures within 7 days of baseline, or not yet recovered from prior surgery.
  10. Any dysphagia, odynophagia, esophageal dysmotility or stricture, known GI malabsorption syndrome, or intractable diarrhea that may significantly alter the absorption of any of the components of SM-88, e.g., cirrhosis.
  11. Known human immunodeficiency (HIV) virus infection.
  12. Known hepatitis B surface antigen (HBsAg) positive.
  13. Known hepatitis C virus (HCV) antibody positive.
  14. Have previously been enrolled in this study or any other study investigating SM-88 or who have previously received any component of SM-88 in a clinical trial.
  15. History of any drug allergies or significant adverse reactions to any of the components of SM-88.
  16. Are currently enrolled in, or have discontinued within 30 days of screening, from a clinical trial involving an investigational product or non-approved use of a drug or device.
  17. Subjects 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.
  18. >10% weight loss over the 28 days prior to consent.
  19. Subject has a variety of factors influencing oral drugs (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc.).
  20. Subjects with central nervous system metastasis; with the exception of subjects who have stable brain metastases as defined as off steroids and no CNS progress for 6 months after CNS treatment.
  21. Pregnant or lactating women.
  22. History of psychiatric drug abuse that cannot be ended, or subjects with mental disorders that will prevent compliance or evaluation including uncontrolled schizophrenia, uncontrolled depression or other uncontrolled disorders.
  23. Subjects with a history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins; or a history of prior acute hepatotoxicity attributable to phenytoin.
  24. Subjects exhibiting idiosyncratic reactions to psoralen compounds.
  25. Subjects with a hypersensitivity to sirolimus.
  26. Subjects 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.
  27. Subjects 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).
  28. Subjects with melanoma or with a history of melanoma, invasive squamous cell carcinomas, or aphakia (due to contraindication for use of methoxsalen).
  29. Subjects 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).
  30. Subjects 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.
  31. Subjects 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]).
  32. Subjects with interstitial lung disease (ILD) (including pneumonitis, bronchiolitis obliterans organizing pneumonia [BOOP], and pulmonary fibrosis).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03512756

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Contact: Maria Loushin 212-461-2198
Contact: Shab Stanicky 212-461-2196

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Sponsors and Collaborators
Tyme, Inc
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Study Director: Giuseppe Del Priore, MD, MPH Tyme, Inc

Additional Information:
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Responsible Party: Tyme, Inc Identifier: NCT03512756     History of Changes
Other Study ID Numbers: Tyme-88-Panc
First Posted: May 1, 2018    Key Record Dates
Last Update Posted: November 21, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tyme, Inc:
Pancreatic cancer
Pancreas cancer
non- toxic
no toxicity

Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Photosensitizing Agents
Dermatologic Agents