- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01490047
Single Dose of Intravenous rhTNF-α and Liposomal Doxorubicin in Patients With Advanced Solid Tumors or Lymphomas
June 15, 2015 updated by: Ludwig Institute for Cancer Research
Phase I Trial of Intravenous Recombinant Human TNF-α and Liposomal Doxorubicin in Patients With Advanced Solid Tumors or Lymphomas
Assess the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of recombinant human tumor necrosis factor-α (rhTNF-α) when given as a single dose intravenously and in combination with liposomal doxorubicin in human subjects
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Study Type
Interventional
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Frankfurt, Germany, D-60488
- Krankenhaus Nordwest
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patient must have a diagnosed solid tumor malignancy or lymphoma indicated for Caelyx treatment.
- Patient is refractory to all lines of standard therapy including biologics, chemo or other therapies, or at least one line of therapy in those patients for whom no standard treatment exists.
- Patient has measurable disease (defined as at least one lesion whose longest diameter can be accurately measured as >1 cm).
- At least 2 weeks has elapsed since the completion of the last cycle of chemotherapy and/or major surgery and the patient is fully recovered from this previous therapy or surgery and any post-surgical complications.
- The patient has a normal cardiac ejection fraction on MUGA or Echocardiogram.
- ECOG performance status of 2 or less.
- Patient is at least 18 years of age.
- Patient is capable of giving informed consent.
- Patient of childbearing potential is using adequate birth control measures (e.g., abstinence, barrier method with spermicide; intrauterine device, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and will continue to use such precautions for 12 months after receiving treatment.
Exclusion Criteria:
- Positive pregnancy test or known pregnancy.
- Participation in any other clinical trial
- Known hypersensitivity to the active substance or to any of the excipients (Albumin).
- Patients exposed to greater than 450 mg/m2 of doxorubicin or Caelyx.
- Patient has a creatinine > 1.5 x the upper limit of normal, chronic renal failure requiring hemodialysis or peritoneal dialysis.
- Platelet count equal to or less than 50,000/mm3, Hemoglobin less than 9.0 g/dL, or an ANC less than 1,000 /mm3.
- Patient has a Sa02 of less than 93% on room air.
- Patient with detectable ascites or portosystemic hypertension or cirrhosis.
- Patient with bilirubin > 2.0, AST or ALT above 2.5X the upper limit of normal, an alkaline phosphatase above 2.5X the upper limit of normal.
- Hypercalcaemia > 12 mg/dl (2.99 mmol/l).
- Patients with contraindications to the use of vasopressor substances.
- Patient has presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening) or bone marrow transplant.
- Patient has a history of a significant medical illness deemed by the principal investigator or sub-investigators as unsuitable for the trial, for example: Significant cardiovascular disease, e.g. congestive heart failure (New York Heart Association Class II, III or IV), severe angina pectoris, cardiac arrhythmias, myocardial infarction within a 3 month period prior to treatment, venous thrombosis, occlusive peripheral arterial disease, recent pulmonary embolism. Severe pulmonary dysfunction. A recent history of, or active peptic ulcer. Severe ascites. Known hypotension.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: rhTNF-α 25 µg/m² + Caelyx 40 mg/m²
Cohort 2: rhTNF-α 25 µg/m² + Caelyx 40 mg/m²
|
Infusion will be done over 60 minutes, preferably via central venous catheter.
Will immediately follow the infusion of Liposomal doxorubicin.
Other Names:
Infusion over 60 minutes
Other Names:
Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.
Other Names:
Recombinant human TNF-α (Beromun) will be diluted in 250 mL of normal saline with albumin (2 mg/mL) to prevent adherence of the protein to the delivery apparatus.
Infusion will be done over 60 minutes, preferably via central venous catheter, including PICC lines.
Other Names:
|
Experimental: rhTNF-α 50 µg/m² + Caelyx 40 mg/m²
Cohort 3: rhTNF-α 50 µg/m² + Caelyx 40 mg/m²
|
Infusion will be done over 60 minutes, preferably via central venous catheter.
Will immediately follow the infusion of Liposomal doxorubicin.
Other Names:
Infusion over 60 minutes
Other Names:
Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.
Other Names:
Recombinant human TNF-α (Beromun) will be diluted in 250 mL of normal saline with albumin (2 mg/mL) to prevent adherence of the protein to the delivery apparatus.
Infusion will be done over 60 minutes, preferably via central venous catheter, including PICC lines.
Other Names:
|
Experimental: rhTNF-α 100 µg/m² + Caelyx 40 mg/m²
Cohort 4: rhTNF-α 100 µg/m² + Caelyx 40 mg/m²
|
Infusion will be done over 60 minutes, preferably via central venous catheter.
Will immediately follow the infusion of Liposomal doxorubicin.
Other Names:
Infusion over 60 minutes
Other Names:
Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.
Other Names:
Recombinant human TNF-α (Beromun) will be diluted in 250 mL of normal saline with albumin (2 mg/mL) to prevent adherence of the protein to the delivery apparatus.
Infusion will be done over 60 minutes, preferably via central venous catheter, including PICC lines.
Other Names:
|
Experimental: rhTNF-α 150 µg/m² + Caelyx 40 mg/m²
Cohort 5: rhTNF-α 150 µg/m² + Caelyx 40 mg/m²
|
Infusion will be done over 60 minutes, preferably via central venous catheter.
Will immediately follow the infusion of Liposomal doxorubicin.
Other Names:
Infusion over 60 minutes
Other Names:
Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.
Other Names:
Recombinant human TNF-α (Beromun) will be diluted in 250 mL of normal saline with albumin (2 mg/mL) to prevent adherence of the protein to the delivery apparatus.
Infusion will be done over 60 minutes, preferably via central venous catheter, including PICC lines.
Other Names:
|
Experimental: rhTNF-α 200 µg/m² + Caelyx 40 mg/m²
Cohort 6: rhTNF-α 200 µg/m² + Caelyx 40 mg/m²
|
Infusion will be done over 60 minutes, preferably via central venous catheter.
Will immediately follow the infusion of Liposomal doxorubicin.
Other Names:
Infusion over 60 minutes
Other Names:
Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.
Other Names:
Recombinant human TNF-α (Beromun) will be diluted in 250 mL of normal saline with albumin (2 mg/mL) to prevent adherence of the protein to the delivery apparatus.
Infusion will be done over 60 minutes, preferably via central venous catheter, including PICC lines.
Other Names:
|
Experimental: rhTNF-α 250 µg/m² + Caelyx 40 mg/m²
Cohort 7: rhTNF-α 250 µg/m² + Caelyx 40 mg/m²
|
Infusion will be done over 60 minutes, preferably via central venous catheter.
Will immediately follow the infusion of Liposomal doxorubicin.
Other Names:
Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.
Other Names:
Recombinant human TNF-α (Beromun) will be diluted in 250 mL of normal saline with albumin (2 mg/mL) to prevent adherence of the protein to the delivery apparatus.
Infusion will be done over 60 minutes, preferably via central venous catheter, including PICC lines.
Other Names:
|
Experimental: rhTNF-α 25 µg/m² + Caelyx 30 mg/m²
Cohort 1 rhTNF-α 25 µg/m² + Caelyx 30 mg/m²
|
Infusion will be done over 60 minutes, preferably via central venous catheter.
Will immediately follow the infusion of Liposomal doxorubicin.
Other Names:
Infusion over 60 minutes
Other Names:
Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.
Other Names:
Recombinant human TNF-α (Beromun) will be diluted in 250 mL of normal saline with albumin (2 mg/mL) to prevent adherence of the protein to the delivery apparatus.
Infusion will be done over 60 minutes, preferably via central venous catheter, including PICC lines.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) of a single dose of intravenous recombinant human tumor necrosis factor-α plus liposomal doxorubicin
Time Frame: Up to 22 days
|
MTD is the dose level below the one that produces 2 or more Dose-Limiting Toxicities
|
Up to 22 days
|
Dose Limiting Toxicity (DLT) of a single dose of intravenous recombinant human tumor necrosis factor-α plus liposomal doxorubicin
Time Frame: up to 22 days
|
Toxicity Criteria will be those listed in NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Any grade 3 cytokine release syndrome/acute infusion reaction or allergic and toxicity Grade 3 and above will be considered a DLT except:
|
up to 22 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall tumor response using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Time Frame: 4 weeks
|
4 weeks
|
|
Caelyx/doxorubicin plasma levels
Time Frame: 0, 24, 48 and 192 hours post-dose
|
Caelyx/doxorubicin plasma levels will be measured at 0, 24, 48 and 192 hours post-dose by fluorimetry (excitation at 470nm, emission 590 nm) after liposomes have been disrupted in 70% ethanol, 0.3 N HCl
|
0, 24, 48 and 192 hours post-dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Elke Jäger, MD, Krankenhaus Nordwest, Frankfurt, Germany
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2013
Study Registration Dates
First Submitted
December 8, 2011
First Submitted That Met QC Criteria
December 9, 2011
First Posted (Estimate)
December 12, 2011
Study Record Updates
Last Update Posted (Estimate)
June 16, 2015
Last Update Submitted That Met QC Criteria
June 15, 2015
Last Verified
June 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gastrointestinal Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Etanercept
- Doxorubicin
- Liposomal doxorubicin
Other Study ID Numbers
- LUD2011-001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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