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

NCT03512756 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: Tyme-88-Panc
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 20

Brief 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, 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.

Conditions

Pancreatic Cancer

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

Outcome Measures

Primary Outcomes (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.

  Up to 12 months

Secondary Outcomes (1)

• Progression Free Survival (PFS)

  Up to 12 months

Study Arms (2)

Part 1 and Part 2 SM-88 Arm

EXPERIMENTAL

(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.

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

Physician's Choice

EXPERIMENTAL

Physician'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.

Drug: Capecitabine, Gemcitabine, and 5-FU

Interventions

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

Daily oral therapy for cancer

Also known as: SM-88, Racemetyrosine

Part 1 and Part 2 SM-88 Arm

Capecitabine, Gemcitabine, and 5-FU DRUG

Investigator choice of the following therapies: Capecitabine, Gemcitabine, and 5-FU

Also known as: Physician's Choice

Physician's Choice

Eligibility Criteria

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

You may qualify if:

• 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.
• \. Participants Have received two (2) and not more than two (2) previous systemic regimens for the treatment of pancreatic adenocarcinoma
• \. Must be eligible to receive one or more of the Physician Choice options.
• \. 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
• \. Must have completed any investigational cancer therapy at least 30 days prior to first dose.
• \. 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.
• \. ≥18 years of age.
• \. ECOG PS ≤2.
• \. 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:
• i. 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Tyme, Inc: lead

Study Sites (20)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

City Of Hope

Duarte, California, 91010, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Hartford Healthcare Cancer

New Britain, Connecticut, 06053, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Advent Health Florida Hospital Tampa

Tampa, Florida, 33613, United States

Location

June E. Nylen Cancer Center

Sioux City, Iowa, 51101, United States

Location

University Medical Center

New Orleans, Louisiana, 70112, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

North Shore Hematology Oncology

East Setauket, New York, 11733, United States

Location

NY Cancer and Blood Specialist

East Setauket, New York, 11733, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Central Park Hematology & Oncology

New York, New York, 10028, United States

Location

Weill Cornell

New York, New York, 10065, United States

Location

New York Cancer and Blood Specialist

The Bronx, New York, 10469, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

Texas Oncology-Baylor

Dallas, Texas, 75246, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Related Publications (1)

• 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.

  PMID: 35499204 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms; Neoplasm Metastasis

Interventions

Methoxsalen; Phenytoin; Sirolimus; racemetyrosine; Capecitabine; Gemcitabine; Fluorouracil

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Furocoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Hydantoins; Imidazolidines; Imidazoles; Azoles; Macrolides; Lactones; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Study Director
• Organization: Tyme, Inc.

Maria.Loushin@TymeInc.com

617-674-9069

Study Officials

• Giuseppe DelPriore, MD, MPH

  Tyme, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: May 1, 2018
• Study Start: March 27, 2018
• Primary Completion: December 28, 2021
• Study Completion: December 28, 2021
• Last Updated: November 6, 2024
• Results First Posted: November 6, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)