ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 2 for:    IMP321 | Germany
Previous Study | Return to List | Next Study

Feasibility and Safety of IMP321 for Advanced Stage Solid Tumors

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.
ClinicalTrials.gov Identifier: NCT03252938
Recruitment Status : Recruiting
First Posted : August 17, 2017
Last Update Posted : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest

August 14, 2017
August 17, 2017
October 26, 2018
August 15, 2017
February 2019   (Final data collection date for primary outcome measure)
Feasibility rate [ Time Frame: 10 weeks of treatment + 2 weeks of safety observation period ]
Rate of patients receiving the protocol treatment without occurrence of a dose limiting toxicity
Same as current
Complete list of historical versions of study NCT03252938 on ClinicalTrials.gov Archive Site
  • Incidence and severity of adverse events according to CTC criteria [ Time Frame: 10 weeks of treatment + 6 months of Follow Up ]
    Incidence and severity of adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
  • Response [ Time Frame: 6 months of Follow Up ]
    Objective response rate according to RECIST 1.1 and endoscopic response criteria
  • Progression free survival [ Time Frame: 6 months of Follow Up ]
    PFS will be measured as time from inclusion until disease progression or death of any cause
  • Overall survival [ Time Frame: 6 months of Follow Up ]
    OS will be measured as time from inclusion to death of any cause
  • Immune response in whole blood and tumor tissue [ Time Frame: 10 weeks of treatment + 6 months of Follow Up ]
    Peripheral blood monocyte number and CD8 T-cell number, associated activation markers, tumor-infiltrating immune cells
  • Safety [ Time Frame: 10 weeks of treatment + 6 months of Follow Up ]
    AEs and SAEs, according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
  • Response [ Time Frame: 6 months of Follow Up ]
    Objective response rate according to RECIST 1.1 and endoscopic response criteria
  • Progression free survival [ Time Frame: 6 months of Follow Up ]
    PFS will be measured as time from inclusion until disease progression or death of any cause
  • Overall survival [ Time Frame: 6 months of Follow Up ]
    OS will be measured as time from inclusion to death of any cause
  • Immune response in whole blood and tumor tissue [ Time Frame: 10 weeks of treatment + 6 months of Follow Up ]
    Peripheral blood monocyte number and CD8 T-cell number, associated activation markers, tumor-infiltrating immune cells
Not Provided
Not Provided
 
Feasibility and Safety of IMP321 for Advanced Stage Solid Tumors
An Explorative, Single Center, Open-labeled, Phase I Study to Evaluate the Feasibility and Safety of Intra-tumoral, Intra-peritoneal, and Subcutaneous Injections With IMP321 (LAG-3Ig Fusion Protein) for Advanced Stage Solid Tumor Entities
This phase I trial aims to investigate a potential enhancement of IMP321 immune-activating effects by new routes of administration: direct injection of IMP321 into the tumor tissue; intra-peritoneal therapy; combination of chemotherapy with active immunotherapy (chemo-immunotherapy)

Up to now, IMP321 is solely administered by sub-cutaneous injection (e.g. on the anterior face of the thigh). In this study, we investigate whether a direct injection of IMP321 into the tumor tissue will be a useful option to improve anti-tumor immune response by placing the immune-therapeutic agent in direct vicinity of immune infiltrates in the tumor bed. This bypasses processes necessary for drug delivery to cells of solid tumors following systemic administration, like transport within vessels, transport across vasculature walls into surrounding tissues, and - in cases of peritoneal metastases - transport through the interstitial space within a tumor. For the latter case, we will also explore if an intra-peritoneal therapy represents a feasible alternative by means of delivering high drug concentrations directly to tumors located in the peritoneal cavity.

Furthermore, we will explore the possibility to extend the positive results obtained by subcutaneous injections of IMP321 in metastatic renal cell and breast carcinomas to further solid tumor entities. In this part of the study, patients will be treated with the standard-of-care (SOC) chemotherapy for their tumor entity along with subcutaneous injections of IMP321.

Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Solid Tumors
  • Peritoneal Carcinomatosis
Drug: IMP321
LAG-3Ig fusion protein, highly potent activator of antigen presenting cells
Other Name: LAG-3Ig fusion protein
  • Experimental: Solid tumors
    Biweekly intra-tumoral injections of escalating doses (6 mg, 12 mg, 24 mg and 30 mg) of IMP321 as a monotherapy (intratumoral injections in parenchymatous organs (e.g. liver, spleen, adrenal gland, pancreas) are not allowed)
    Intervention: Drug: IMP321
  • Experimental: Solid tumors + peritoneal carcinomatosis
    Biweekly intra-peritoneal, escalating doses of IMP321 (1 mg, 3 mg, 6 mg, 12 mg and 30 mg)
    Intervention: Drug: IMP321
  • Experimental: solid tumors +chemotherapy
    Subcutaneous (s.c.) injections with the optimal dose of IMP321 defined in the AIPAC trial for a maximum of 24 weeks
    Intervention: Drug: IMP321
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
38
Same as current
March 2020
February 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Histologically confirmed locally advanced or metastatic solid tumor
  2. Tumor is accessible for repeated injections and biopsies (only for Stratum A)
  3. Peritoneal carcinomatosis (only for Stratum B)
  4. Patient failed standard therapy or refused standard therapy or is intolerable towards standard therapy (Strata A, B) or who receives standard-of-care chemotherapy indicated for his/her tumor entity (only for Stratum C)
  5. Patient does not receive a concurrent chemotherapy (only for Strata A and B)
  6. Female and male patients ≥ 18 years. Patients in reproductive age must be willing to use highly effective contraception during the study and 3 months after the end of the study (appropriate contraception is defined as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomized partner, bilateral tubal occlusion, sexual abstinence. If an oral contraception is used, a barrier method of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) has to be applied additionally.).. Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start.
  7. ECOG 0 or 1
  8. Adequate hematological, hepatic and renal function parameters:

    • ANC (absolute neutrophil count) ≥ 1.500/µl
    • Leukocytes ≥ 3.000/µl
    • Platelets ≥ 75.000/µl
    • Serum creatinine ≤ 1.5 x upper limit of normal, or GFR ≥ 50 ml/min
    • Bilirubin ≤ 1.5 - 3 x upper limit of normal
    • AST and ALT ≤ 3 x upper limit of normal (≤ 5 x if liver metastases are present)
    • Alkaline phosphatase ≤ 6 x upper limit of normal
    • Hemoglobin ≥ 9g/dL
  9. Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin/ phenprocoumon must be switched to low molecular weight heparin and have achieved stable coagulation profile.
  10. Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures

Exclusion Criteria:

  1. Inability to understand the aims of the study and/or protocol procedures
  2. Bleeding ulcerative tumors or tumors requiring intratumoral injections of study drug into parenchymatous organs such as, but limited to liver, spleen or pancreas (only for Stratum A)
  3. Patients with contraindication versus a laparoscopy or refusing a laparoscopy (only for Stratum B)
  4. Hypersensitivity to IMP321 or any ingredient of the injection solution
  5. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  6. Any other concurrent antineoplastic treatment including irradiation (only Strata A and B)
  7. Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
  8. Cirrhosis of the liver (Child > Grade A), pronounced alcohol abuse with anticipated detoxification, severe pulmonary infection with considerable reduction of pulmonary function
  9. Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA III-IV
  10. Clinically active brain metastases, defined as untreated symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.

    Subjects with treated brain metastases that are no longer symptomatic and require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy and have no evidence of disease progression on imaging studies (MRI/CT scan).

  11. Chronic inflammatory bowel disease
  12. Active infection requiring intravenous antibiotics at the start of study treatment or chronic infection
  13. QTcF >480 ms, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP)
  14. Uncontrolled electrolyte disorders that can worsen the effects of a QTc-prolonging drug (e.g., hypocalcaemia, hypokalaemia, hypomagnesemia)
  15. Positive test for human immunodeficiency virus (HIV)
  16. Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test) or hepatitis C Note: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible. Note: Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid (RNA).
  17. Active tuberculosis
  18. Active autoimmune disease requiring immunosuppressive therapy
  19. Administration of a live, attenuated vaccine within four weeks prior to start of maintenance treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study.
  20. Any condition requiring continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks prior to first dose of study treatment. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
  21. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within four weeks or five half-lives of the drug, whichever is shorter, prior to start of study treatment
  22. Any previous venous thromboembolism > National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 within the last 12 months
  23. Past history of severe allergic episodes and/ or Quincke's oedema
  24. Prior organ transplantation or stem cell transplantation
  25. On-treatment participation in another clinical study in the period 30 days prior to start of study treatment and during the study
  26. Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)
  27. Pregnancy or lactation
  28. Planned intratumoral injections in parenchymatous organs (e.g. liver, spleen, adrenal gland, pancreas)
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Salah-Eddin Al-Batran, MD +49 69 7601 ext 4420 albatran.salah@khnw.de
Contact: Regina Eickhoff, PhD +49 69 7601 ext 4165 eickhoff.regina@khnw.de
Germany
 
 
NCT03252938
INSIGHT
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Not Provided
IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest
IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest
Not Provided
Principal Investigator: Salah-Eddin Al-Batran, MD Institute of Clinical Cancer Research (IKF), UCT - University Cancer Center, Frankfurt, Germany
IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP