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

Ludwig Institute for Cancer Research

Status and phase: Withdrawn; Phase 1

Conditions: Lymphomas; Solid Tumors

Treatments: Drug: Caelyx; Drug: Recombinant human TNF-α; Drug: Liposomal doxorubicin

Study type: Interventional

Funder types: Other

Identifiers

NCT01490047

LUD2011-001

Details and patient eligibility

About

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

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 7 patient groups

rhTNF-α 25 µg/m² + Caelyx 40 mg/m²

Experimental group

Description:

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

Treatment:

Drug: Liposomal doxorubicin

Drug: Recombinant human TNF-α

Drug: Caelyx

Drug: Recombinant human TNF-α

rhTNF-α 50 µg/m² + Caelyx 40 mg/m²

Experimental group

Description:

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

Treatment:

Drug: Liposomal doxorubicin

Drug: Recombinant human TNF-α

Drug: Caelyx

Drug: Recombinant human TNF-α

rhTNF-α 100 µg/m² + Caelyx 40 mg/m²

Experimental group

Description:

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

Treatment:

Drug: Liposomal doxorubicin

Drug: Recombinant human TNF-α

Drug: Caelyx

Drug: Recombinant human TNF-α

rhTNF-α 150 µg/m² + Caelyx 40 mg/m²

Experimental group

Description:

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

Treatment:

Drug: Liposomal doxorubicin

Drug: Recombinant human TNF-α

Drug: Caelyx

Drug: Recombinant human TNF-α

rhTNF-α 200 µg/m² + Caelyx 40 mg/m²

Experimental group

Description:

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

Treatment:

Drug: Liposomal doxorubicin

Drug: Recombinant human TNF-α

Drug: Caelyx

Drug: Recombinant human TNF-α

rhTNF-α 250 µg/m² + Caelyx 40 mg/m²

Experimental group

Description:

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

Treatment:

Drug: Recombinant human TNF-α

Drug: Caelyx

Drug: Recombinant human TNF-α

rhTNF-α 25 µg/m² + Caelyx 30 mg/m²

Experimental group

Description:

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

Treatment:

Drug: Liposomal doxorubicin

Drug: Recombinant human TNF-α

Drug: Caelyx

Drug: Recombinant human TNF-α