Single Dose of Intravenous rhTNF-α and Liposomal Doxorubicin in Patients With Advanced Solid Tumors or Lymphomas

NCT ID: NCT01490047

Last Updated: 2015-06-16

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31

Brief Summary

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

Conditions

Solid Tumors; Lymphomas

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rhTNF-α 25 µg/m² + Caelyx 40 mg/m²

Cohort 2: rhTNF-α 25 µg/m² + Caelyx 40 mg/m²

Group Type: EXPERIMENTAL

Recombinant human TNF-α

Intervention Type: DRUG

Infusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin.

Liposomal doxorubicin

Intervention Type: DRUG

Infusion over 60 minutes

Caelyx

Intervention Type: DRUG

Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.

Recombinant human TNF-α

Intervention Type: DRUG

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.

rhTNF-α 50 µg/m² + Caelyx 40 mg/m²

Cohort 3: rhTNF-α 50 µg/m² + Caelyx 40 mg/m²

Group Type: EXPERIMENTAL

Recombinant human TNF-α

Intervention Type: DRUG

Infusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin.

Liposomal doxorubicin

Intervention Type: DRUG

Infusion over 60 minutes

Caelyx

Intervention Type: DRUG

Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.

Recombinant human TNF-α

Intervention Type: DRUG

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.

rhTNF-α 100 µg/m² + Caelyx 40 mg/m²

Cohort 4: rhTNF-α 100 µg/m² + Caelyx 40 mg/m²

Group Type: EXPERIMENTAL

Recombinant human TNF-α

Intervention Type: DRUG

Infusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin.

Liposomal doxorubicin

Intervention Type: DRUG

Infusion over 60 minutes

Caelyx

Intervention Type: DRUG

Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.

Recombinant human TNF-α

Intervention Type: DRUG

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.

rhTNF-α 150 µg/m² + Caelyx 40 mg/m²

Cohort 5: rhTNF-α 150 µg/m² + Caelyx 40 mg/m²

Group Type: EXPERIMENTAL

Recombinant human TNF-α

Intervention Type: DRUG

Infusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin.

Liposomal doxorubicin

Intervention Type: DRUG

Infusion over 60 minutes

Caelyx

Intervention Type: DRUG

Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.

Recombinant human TNF-α

Intervention Type: DRUG

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.

rhTNF-α 200 µg/m² + Caelyx 40 mg/m²

Cohort 6: rhTNF-α 200 µg/m² + Caelyx 40 mg/m²

Group Type: EXPERIMENTAL

Recombinant human TNF-α

Intervention Type: DRUG

Infusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin.

Liposomal doxorubicin

Intervention Type: DRUG

Infusion over 60 minutes

Caelyx

Intervention Type: DRUG

Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.

Recombinant human TNF-α

Intervention Type: DRUG

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.

rhTNF-α 250 µg/m² + Caelyx 40 mg/m²

Cohort 7: rhTNF-α 250 µg/m² + Caelyx 40 mg/m²

Group Type: EXPERIMENTAL

Recombinant human TNF-α

Intervention Type: DRUG

Infusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin.

Caelyx

Intervention Type: DRUG

Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.

Recombinant human TNF-α

Intervention Type: DRUG

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.

rhTNF-α 25 µg/m² + Caelyx 30 mg/m²

Cohort 1 rhTNF-α 25 µg/m² + Caelyx 30 mg/m²

Group Type: EXPERIMENTAL

Recombinant human TNF-α

Intervention Type: DRUG

Infusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin.

Liposomal doxorubicin

Intervention Type: DRUG

Infusion over 60 minutes

Caelyx

Intervention Type: DRUG

Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.

Recombinant human TNF-α

Intervention Type: DRUG

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.

Interventions

Recombinant human TNF-α

Infusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin.

Intervention Type: DRUG

Liposomal doxorubicin

Infusion over 60 minutes

Intervention Type: DRUG

Caelyx

Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.

Intervention Type: DRUG

Recombinant human TNF-α

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.

Intervention Type: DRUG

Other Intervention Names

Beromun; Caelyx; liposomal doxorubicin; Beromun

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: collaborator

Ludwig Institute for Cancer Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elke Jäger, MD

Role: PRINCIPAL_INVESTIGATOR

Krankenhaus Nordwest, Frankfurt, Germany

Locations

Krankenhaus Nordwest

Frankfurt, , Germany

Countries

Germany

Other Identifiers

LUD2011-001

Identifier Type: -

Identifier Source: org_study_id