Clinical trial NCT01490047: Single Dose of Intravenous rhTNF-α and Liposomal Doxorubicin in Patients With Advanced Solid Tumors or Lymphomas
Official title: Phase I Trial of Intravenous Recombinant Human TNF-α and Liposomal Doxorubicin in Patients With Advanced Solid Tumors or Lymphomas
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Solid Tumors
Lymphomas
Lead sponsor: Ludwig Institute for Cancer Research
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
First posted: 2011-12-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of a single dose of intravenous recombinant human tumor necrosis factor-α plus liposomal doxorubicin
timeFrame: Up to 22 days
measure: Dose Limiting Toxicity (DLT) of a single dose of intravenous recombinant human tumor necrosis factor-α plus liposomal doxorubicin
timeFrame: up to 22 days
Secondary outcomes:
measure: Overall tumor response using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
timeFrame: 4 weeks
measure: Caelyx/doxorubicin plasma levels
timeFrame: 0, 24, 48 and 192 hours post-dose
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest
Study officials:
affiliation: Krankenhaus Nordwest, Frankfurt, Germany
name: Elke Jäger, MD
role: PRINCIPAL_INVESTIGATOR
References: