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Phase I/II Trial of Intralesional Administration of RGT100

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ClinicalTrials.gov Identifier: NCT03065023
Recruitment Status : Terminated (Group B was not started. Development will continue with new protocol.)
First Posted : February 27, 2017
Last Update Posted : August 2, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a Phase I/II multicenter, first-in-human open-label, dose escalation study to evaluate the safety, tolerability, and anti-tumor activity of intratumoral/intralesional injections of RGT100-PEI in subjects with selected advanced or recurrent tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: RGT100-PEI Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The study will be conducted in 2 groups

  • Group A: subjects with transdermally/transmucosally injectable tumors
  • Group B: subjects with injectable liver tumors or liver metastases
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Multicenter, Open-label, Clinical Trial of Intratumoral/Intralesional Administration of RGT100 in Subjects With Advanced or Recurrent Tumors
Actual Study Start Date : April 25, 2017
Actual Primary Completion Date : May 18, 2018
Actual Study Completion Date : May 18, 2018

Arm Intervention/treatment
Experimental: Group A: Cutaenous lesions

Subjects with transdermally/transmucosally injectable tumors including cutaneous, sub-cutaneous or lymph node injectable tumors.

RGT100-PEI will be injected intratumorally/intralesionally twice a week over a period of 4 weeks.

Drug: RGT100-PEI
RGT100-PEI with a fixed concentration of 0.2 mg/mL

Experimental: Group B: Liver lesions

Subjects with injectable liver tumors or liver metastases.

RGT100-PEI will be injected into liver lesions once a week over a period of 4 weeks.

Drug: RGT100-PEI
RGT100-PEI with a fixed concentration of 0.2 mg/mL




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: For the treatment duration of 4 weeks ]
  2. Occurrence of serious adverse events (SAEs) [ Time Frame: For the treatment duration of 4 weeks ]
  3. Occurrence of treatment discontinuation due to treatment-related AEs [ Time Frame: For the treatment duration of 4 weeks ]
  4. Incidence and severity of dose-limiting toxicities (DLTs) [ Time Frame: For the treatment duration of 4 weeks ]

Secondary Outcome Measures :
  1. Objective response rate as evaluated radiologically using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) [ Time Frame: Up to 60 days (Week 13) after last injection ]

Other Outcome Measures:
  1. Type of cytokine release in plasma upon treatment [ Time Frame: Until 30 days (Week 9) after last injection ]
  2. Plasma concentrations of RGT100-PEI (AUC) [ Time Frame: For the treatment duration of 4 weeks ]
  3. Plasma concentrations of RGT100-PEI (Cmax) [ Time Frame: For the treatment duration of 4 weeks ]
  4. Evidence of immune infiltration of injected tumors [ Time Frame: For the treatment duration of 4 weeks ]
    Presence of tumor infiltrating immune cells in biopsy (e.g. CD4, CD8)



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:

  1. Male or female aged ≥ 18 years
  2. Subjects with histologically or cytologically confirmed diagnosis of advanced or recurrent tumors (including lymphomas) for whom all standard treatments have been used or are not feasible and RGT100-PEI is a suitable treatment option and:

    1. For Group A: has cutaneous, sub-cutaneous (s.c.), or lymph node injectable tumors
    2. For Group B: has injectable liver tumors or liver metastases
  3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  4. Life expectancy > 3 months as assessed by the Investigator
  5. Adequate organ function:

    1. Bone marrow function: Hemoglobin ≥ 10 g/dL (pre-treatment transfusion allowed); lymphocyte count ≥ 0.5 × 109/L; absolute neutrophil count ≥ 0.5 × 109/L; platelet count ≥ 75 × 109/L
    2. Hepatic function: AST and ALT ≤ 2 × upper limit of normal (ULN) (3 × ULN in the case of liver metastases); bilirubin ≤ 1.5 × ULN (2 × ULN in case of liver metastases)
    3. Renal function: creatinine < 1.5 × ULN and/or creatinine clearance ≥ 50 mL/min (Cockroft and Gault)
  6. Negative serum pregnancy test within 2 weeks before first dose of study drug if the subject is a woman of childbearing potential. Subjects and subjects' partners of childbearing potential must agree to use birth control consistently and correctly during the study and for at least 6 months after the last study drug application.
  7. At least 1 measurable lesion per RECIST 1.1 and 1 separate injectable lesion with diameter ≥ 1 cm but < 7 cm
  8. Ability to provide written informed consent before any study drug-related screening procedures being performed

Exclusion Criteria:

  1. Any tumor-directed therapy within 4 weeks before study treatment
  2. Treatment with investigational drugs within 4 weeks before study enrolment
  3. Systemic steroids at a dose of > 10 mg of prednisolone, > 2 mg of dexamethasone a day or equivalent, except topical (inhaled, topical, nasal) for the last 28 days and ongoing
  4. Subjects with rapidly progressing disease (as determined by the Investigator)
  5. Ongoing immune-related adverse events (irAEs) and/or AEs ≥ grade 2 not resolved from previous therapies except vitiligo, stable neuropathy grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy
  6. Within 4 weeks of major surgery
  7. Prior splenectomy
  8. Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy
  9. Primary or secondary immune deficiency
  10. Active allergy requiring systemic medication or active infections requiring anti-infectious therapy
  11. Seropositive (except after vaccination) for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
  12. Clinically significant cardiac disease including heart failure (New York Heart Association, Class III or IV), pre-existing arrhythmia, uncontrolled angina pectoris, or myocardial infarction within 1 year before study entry
  13. Dementia or altered mental status that would prohibit informed consent
  14. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator
  15. History of stroke, seizures, encephalitis, or multiple sclerosis
  16. Gastric ulcer or inflammatory bowel disease or Crohn's disease or ulcerative colitis in the last 6 months
  17. Active drug or alcohol abuse
  18. Pregnant or breast feeding

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): NCT03065023


Locations
Germany
Universitätsklinikum Carl Gustav Carus - Phase I Unit
Dresden, Germany
Universitätsklinikum Essen
Essen, Germany
National Center for Tumor Diseases
Heidelberg, Germany
Spain
START - Fundación Jiménez Díaz - Phase I Unit
Madrid, Spain
START - Hospital Universitario HM Sanchinarro - Phase I Unit
Madrid, Spain
United Kingdom
University of Oxford Department of Oncology, Churchill Hospital
Oxford, United Kingdom
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Manuela Niewel, Dr. Rigontec GMBH
Principal Investigator: Mark Middleton, Prof. Dr. University of Oxford Department of Oncology, Churchill Hospital

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03065023     History of Changes
Other Study ID Numbers: 4621-001
2016-003028-22 ( EudraCT Number )
RGT100-001 ( Other Identifier: Rigotec GMBH Protocol ID )
First Posted: February 27, 2017    Key Record Dates
Last Update Posted: August 2, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Merck Sharp & Dohme Corp.:
advanced tumor
intratumoral injection
intralesional injection