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A Phase 2 Study of siG12D LODER in Combination With Chemotherapy in Patients With Locally Advanced Pancreatic Cancer (PROTACT)

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ClinicalTrials.gov Identifier: NCT01676259
Recruitment Status : Recruiting
First Posted : August 30, 2012
Last Update Posted : July 2, 2021
Sponsor:
Information provided by (Responsible Party):
Silenseed Ltd

Brief Summary:

In this Phase II study a dose of 2.8 mg (eight 0.35 mg siG12D-LODERs) will be administered in 12-week cycles to patients with unresectable or borderline resectable locally advanced pancreatic cancer combined with chemotherapy treatment.

Primary Outcome:

- ORR at 6 months.


Condition or disease Intervention/treatment Phase
Pancreatic Ductal Adenocarcinoma Pancreatic Cancer Drug: siG12D-LODER Drug: Gemcitabine+nab-Paclitaxel Drug: Folfirinox Phase 2

Detailed Description:

In this Phase II study a dose of 2.8 mg (eight 0.35 mg siG12D-LODERs) will be administered in 12-week cycles to patients with unresectable or borderline resectable LAPC combined with chemotherapy treatment (Gemcitabine+nab-Paclitaxel or Folfirinox or modified Folfirinox). This will be a study to assess the response rate of the siG12D-LODER in patients with unresectable or borderline resectable LAPC. The study is of a single arm design with one arm receiving siG12D-LODER + chemotherapy.

The investigational agent siG12D-LODER is a miniature biodegradable bio polymeric matrix that encompasses the drug, designed and produced by Silenseed Ltd. The implantation of LODERs is selected to meet current gastroenterology endoscopic ultrasound (EUS) biopsy procedures, proved to be highly effective and safe.

siG12D-LODER has been studied in the escalating dose Phase I study of 15 patients, and results showed high safety and tolerability profiles, with no single DLT.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Multinational, Multi-Center, Phase 2, Single-Arm, Open-Label Study Evaluating the Efficacy, Safety and Tolerability of siG12D-LODER in Combination With Standard of Care Chemotherapy in the Treatment of Patients With Locally Advanced Pancreatic Cancer
Actual Study Start Date : March 7, 2018
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: siG12D-LODER + chemotherapy
Eight siG12D-LODER+Gemcitabine+nab-Paclitaxel or Eight siG12D-LODER+Folfirinox or Eight siG12D-LODER+modifide Folfirinox
Drug: siG12D-LODER
The implantation of siG12D-LODERs is selected to meet current gastroenterology endoscopic ultrasound (EUS) biopsy procedures, proved to be highly effective and safe.

Drug: Gemcitabine+nab-Paclitaxel
Gemcitabine+nab-Paclitaxel
Other Name: Chemotherapy

Drug: Folfirinox
Folfirinox or modified Folfirinox
Other Name: Chemotherapy




Primary Outcome Measures :
  1. ORR at 6 months [ Time Frame: One year ]


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
Criteria

Inclusion Criteria:

Age

1. Subject must be 18 years of age or older at the time of signing the informed consent.

Type of Subject and Disease Characteristics

  1. Histologically or cytologically confirmed adenocarcinoma of the pancreas.
  2. Locally advanced pancreatic cancer stage III according to The American Joint Committee on Cancer (AJCC) and defined as T4, N (any) and M0, according to the three factors, T (tumor), N (node involvement), and M (metastases), of the National Comprehensive Cancer Network TNM classification.
  3. Allocated to receive one of the following chemotherapies: gemcitabine plus nab-paclitaxel, FOLFIRINOX or modified FOLFIRIONOX as first line treatment for pancreatic cancer.
  4. Have a target tumor that is accessible for intratumoral administration by EUS as determined by the radiologist/gastroenterologist performing the EUS intratumoral administration, according to The American Society for Gastrointestinal Endoscopy (ASGE) guidelines (https://www.asge.org/home/practice-support/guidelines).
  5. Have measurable disease. Subject will have a histologically-confirmed disease and must have clinically and/or radiographically documented measurable primary disease according to RECIST v1.1. At least one site of disease must be unidimensionally measurable.

    Diagnostic Assessments

  6. Eastern Cooperative Oncology Group (ECOG) Performance Scale of ≤ 1.
  7. Demonstrate adequate organ function as defined below:

    • serum creatinine <1.6 mg/dL
    • international normalized ratio (INR) < 1.5 U
    • absolute neutrophil count (ANC) > 1.5 x 109/L
    • platelets ≥ 100 x 109/L
    • hemoglobin ≥ 9 mg/dL
    • alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 5 times upper limit of normal (ULN)
    • bilirubin ≤ 1.5 x ULN Sex
  8. Male and/or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  9. Women of childbearing potential (WOCBP): a negative serum or urine pregnancy test during screening.
  10. Subject of childbearing potential, if sexually active (both men and women) must agree to use a barrier method of contraception, from the time of administration of the first treatment and for at least 8 weeks after EOT visit day.

    Informed Consent

  11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

Subjects are excluded from the study if any of the following criteria apply:

Medical Conditions

  1. Subjects with resectable pancreatic cancer.
  2. Evidence of metastatic disease.
  3. Other malignancy that would interfere with the current intervention.
  4. Any evidence of ascites (beyond trace).
  5. Bulky celiac adenopathy (≥2.5 cm) or non-adenocarcinoma histology.
  6. Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancers from which the subject has been disease-free for at least 2 years.
  7. History of clinically significant coagulopathy.
  8. Major surgery, other than diagnostic surgery, within 4 weeks prior to study entry without complete recovery.
  9. New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 4 months prior to the first chemotherapy cycle Day 1, unstable arrhythmia or symptomatic peripheral arterial vascular disease.
  10. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
  11. Known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus.
  12. Females who are pregnant or breast-feeding.
  13. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study.

    Prior/Concomitant Therapy

  14. Any prior therapy for the treatment of pancreatic malignancy (including chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether conventional or investigational).
  15. Prior therapy with any hypoxic cytotoxic agent (hypoxia-targeting drugs). Prior/Concurrent Clinical Study Experience
  16. Subjects who are participating or participated in an investigational drug or device study (within 28 days prior to study entry from the last study dose date).

    Other Exclusions:

  17. Unwillingness or inability to comply with the study protocol for any reason.
  18. Known allergy to sesame oil.

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 ClinicalTrials.gov identifier (NCT number): NCT01676259


Contacts
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Contact: Orit Pollack-Shragai, MSc, MBA +972-52-8466267 orit@silenseed.com

Locations
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United States, New Jersey
Hackensack Meridian Health Active, not recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
The Mount Sinai Hospital Recruiting
New York, New York, United States, 10029
Contact: Celina Ang, MD    212-824-8551    celina.ang@mssm.edu   
Contact: Christopher DiMaio, MD    212-241-7531    christopher.dimaio@mountsinai.org   
Principal Investigator: Celina Ang, MD         
Principal Investigator: Christopher J DiMaio, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Eileen M O'Reilly, MD    646-888-4182    oreillye@mskcc.org   
Contact: Anna M Varghese, MD    646-888-4308    VarghesA@mskcc.org   
Principal Investigator: Eileen M. O'Reilly, MD         
Principal Investigator: Anna M Varghese, MD         
Principal Investigator: Mark A Schattner, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Milind Javle, MD    713-792-5434    mjavle@mdanderson.org   
Contact: Manoop Bhutani, MD    1-713-792-2121    Manoop.Bhutani@mdanderson.org   
Principal Investigator: Milind Javle, MD         
Principal Investigator: Manoop Bhutani, MD         
Israel
Rambam Medical Center Recruiting
Haifa, Israel, 3525408
Contact: Valerya Semenysty, MD    +972-4-7776419    semenysty@rambam.health.gov.il   
Contact: Iyad Khamaysi, MD    +972-4-7773626    z_khamaysi@rambam.health.gov.ill   
Principal Investigator: Valerya Semenysty, MD         
Sub-Investigator: Iyad Khamaysi, MD         
Rabin Medical Center Completed
Petah Tikva, Israel, 49102
Sheba Medical Center (Tel H'shomer) Recruiting
Ramat Gan, Israel, 52621
Contact: Talia Golan, MD    +972-3-5305338    Talia.Golan@sheba.health.gov.il   
Contact: Maor Lahav, MD    +972- 3-5305875    Maor.Lahav@sheba.health.gov.il   
Principal Investigator: Talia Golan, MD         
Sub-Investigator: Maor Lahav, MD         
Sourasky MC (Ichilov) Tel Aviv Israel Recruiting
Tel Aviv, Israel
Contact: Ravit Geva, M.D    972- 36973082    ravitg@tlvmc.gov.il   
Contact: Adam Phillips, M.D       adamp@tlvmc.gov.il   
Assaf Harofeh Medical Center Active, not recruiting
Tzrifin, Israel, 70300
Sponsors and Collaborators
Silenseed Ltd
Investigators
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Principal Investigator: Eileen M O'Reilly, MD Memorial Sloan Kettering Cancer Center
Principal Investigator: Talia Golan, MD Sheba Medical Center
Additional Information:
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Responsible Party: Silenseed Ltd
ClinicalTrials.gov Identifier: NCT01676259    
Other Study ID Numbers: SLSG12D-P2
First Posted: August 30, 2012    Key Record Dates
Last Update Posted: July 2, 2021
Last Verified: June 2021

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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 Silenseed Ltd:
siRNA
RNA interference (RNAi)
Cancer
Pancreatic ductal adenocarcinoma
Locally Advanced Pancreatic cancer
Solid tumor
Non operable pancreatic ductal adenocarcinoma
Borderline resectable
Additional relevant MeSH terms:
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Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Folfirinox
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs