Solid TumorsPhase 1NCT01490047
Single Dose of Intravenous rhTNF-α and Liposomal Doxorubicin in Patients With Advanced Solid Tumors or Lymphomas
A Phase 1 study testing Recombinant human TNF-α, Liposomal doxorubicin and Caelyx in people with Solid Tumors and Lymphomas, run by Ludwig Institute for Cancer Research at 1 site in Germany.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Lymphomas
- What is being tested?
- Recombinant human TNF-α, Liposomal doxorubicin and Caelyx
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2013to not given
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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 locations and contacts
1 site in 1 country.
About this study
Official title: 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
- Conditions
- Solid Tumors, Lymphomas
- Being tested
- Recombinant human TNF-α, Liposomal doxorubicin, Caelyx
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human TNF-αDrug
Also called Beromun
Infusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin.
Liposomal doxorubicinDrug
Also called Caelyx
Infusion over 60 minutes
CaelyxDrug
Also called liposomal doxorubicin
Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.
Recombinant human TNF-αDrug
Also called Beromun
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.
| Study group | Role | What they receive |
|---|---|---|
| rhTNF-α 25 µg/m² + Caelyx 40 mg/m² | Experimental | Cohort 2: rhTNF-α 25 µg/m² + Caelyx 40 mg/m² Receives: Drug: Recombinant human TNF-α; Drug: Liposomal doxorubicin; Drug: Caelyx |
| rhTNF-α 50 µg/m² + Caelyx 40 mg/m² | Experimental | Cohort 3: rhTNF-α 50 µg/m² + Caelyx 40 mg/m² Receives: Drug: Recombinant human TNF-α; Drug: Liposomal doxorubicin; Drug: Caelyx |
| rhTNF-α 100 µg/m² + Caelyx 40 mg/m² | Experimental | Cohort 4: rhTNF-α 100 µg/m² + Caelyx 40 mg/m² Receives: Drug: Recombinant human TNF-α; Drug: Liposomal doxorubicin; Drug: Caelyx |
| rhTNF-α 150 µg/m² + Caelyx 40 mg/m² | Experimental | Cohort 5: rhTNF-α 150 µg/m² + Caelyx 40 mg/m² Receives: Drug: Recombinant human TNF-α; Drug: Liposomal doxorubicin; Drug: Caelyx |
| rhTNF-α 200 µg/m² + Caelyx 40 mg/m² | Experimental | Cohort 6: rhTNF-α 200 µg/m² + Caelyx 40 mg/m² Receives: Drug: Recombinant human TNF-α; Drug: Liposomal doxorubicin; Drug: Caelyx |
| rhTNF-α 250 µg/m² + Caelyx 40 mg/m² | Experimental | Cohort 7: rhTNF-α 250 µg/m² + Caelyx 40 mg/m² Receives: Drug: Recombinant human TNF-α; Drug: Caelyx |
| rhTNF-α 25 µg/m² + Caelyx 30 mg/m² | Experimental | Cohort 1 rhTNF-α 25 µg/m² + Caelyx 30 mg/m² Receives: Drug: Recombinant human TNF-α; Drug: Liposomal doxorubicin; Drug: Caelyx |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of a single dose of intravenous recombinant human tumor necrosis factor-α plus liposomal doxorubicin
MTD is the dose level below the one that produces 2 or more Dose-Limiting Toxicities
Measured: Up to 22 days
Dose Limiting Toxicity (DLT) of a single dose of intravenous recombinant human tumor necrosis factor-α plus liposomal doxorubicin
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:
- Grade 3 toxicities that recover to grade 1 or less within 48 hours after standard supportive treatment.
- Grade 4 neutropenia that recovers within 14 days.
- Grade 4 thrombocytopenia that recovers within 14 days.
- Grade 4 anemia that recovers within 14 days.
Measured: up to 22 days
Secondary outcomes (2)
Overall tumor response using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Measured: 4 weeks
Caelyx/doxorubicin plasma levels
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
Measured: 0, 24, 48 and 192 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2011 (estimated)
- Study startJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig Institute for Cancer Research
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University
- Responsible party
- Sponsor
- Investigators
- Elke Jäger, MD, Principal investigator, Krankenhaus Nordwest, Frankfurt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01490047
- Sponsor's protocol ID
- LUD2011-001
- Status last verified
- Jun 2015
- First submitted
- 8 Dec 2011
- Last updated
- 16 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Intravenous Recombinant Human TNF-α and Liposomal Doxorubicin in Patients With Advanced Solid Tumors or Lymphomas
- ClinicalTrials.gov ID
- NCT01490047
- Acronym / sponsor ID
- LUD2011-001
- Conditions
- Solid Tumors, Lymphomas
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ludwig Institute for Cancer ResearchUniversity, hospital or other
- Collaborators
- Johns Hopkins University
- Study start
- Jan 2013
- First posted
- 12 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| rhTNF-α 25 µg/m² + Caelyx 40 mg/m² | Experimental | Drug: Recombinant human TNF-α, Drug: Liposomal doxorubicin, Drug: CaelyxCohort 2: rhTNF-α 25 µg/m² + Caelyx 40 mg/m² |
| rhTNF-α 50 µg/m² + Caelyx 40 mg/m² | Experimental | Drug: Recombinant human TNF-α, Drug: Liposomal doxorubicin, Drug: CaelyxCohort 3: rhTNF-α 50 µg/m² + Caelyx 40 mg/m² |
| rhTNF-α 100 µg/m² + Caelyx 40 mg/m² | Experimental | Drug: Recombinant human TNF-α, Drug: Liposomal doxorubicin, Drug: CaelyxCohort 4: rhTNF-α 100 µg/m² + Caelyx 40 mg/m² |
| rhTNF-α 150 µg/m² + Caelyx 40 mg/m² | Experimental | Drug: Recombinant human TNF-α, Drug: Liposomal doxorubicin, Drug: CaelyxCohort 5: rhTNF-α 150 µg/m² + Caelyx 40 mg/m² |
| rhTNF-α 200 µg/m² + Caelyx 40 mg/m² | Experimental | Drug: Recombinant human TNF-α, Drug: Liposomal doxorubicin, Drug: CaelyxCohort 6: rhTNF-α 200 µg/m² + Caelyx 40 mg/m² |
| rhTNF-α 250 µg/m² + Caelyx 40 mg/m² | Experimental | Drug: Recombinant human TNF-α, Drug: CaelyxCohort 7: rhTNF-α 250 µg/m² + Caelyx 40 mg/m² |
| rhTNF-α 25 µg/m² + Caelyx 30 mg/m² | Experimental | Drug: Recombinant human TNF-α, Drug: Liposomal doxorubicin, Drug: CaelyxCohort 1 rhTNF-α 25 µg/m² + Caelyx 30 mg/m² |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant human TNF-αAlso: BeromunInfusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin. | Drug | rhTNF-α 100 µg/m² + Caelyx 40 mg/m², rhTNF-α 150 µg/m² + Caelyx 40 mg/m², rhTNF-α 200 µg/m² + Caelyx 40 mg/m², rhTNF-α 25 µg/m² + Caelyx 30 mg/m², rhTNF-α 25 µg/m² + Caelyx 40 mg/m², rhTNF-α 250 µg/m² + Caelyx 40 mg/m², rhTNF-α 50 µg/m² + Caelyx 40 mg/m² |
| Liposomal doxorubicinAlso: CaelyxInfusion over 60 minutes | Drug | rhTNF-α 100 µg/m² + Caelyx 40 mg/m², rhTNF-α 150 µg/m² + Caelyx 40 mg/m², rhTNF-α 200 µg/m² + Caelyx 40 mg/m², rhTNF-α 25 µg/m² + Caelyx 30 mg/m², rhTNF-α 25 µg/m² + Caelyx 40 mg/m², rhTNF-α 50 µg/m² + Caelyx 40 mg/m² |
| CaelyxAlso: liposomal doxorubicinAdministration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α. | Drug | rhTNF-α 100 µg/m² + Caelyx 40 mg/m², rhTNF-α 150 µg/m² + Caelyx 40 mg/m², rhTNF-α 200 µg/m² + Caelyx 40 mg/m², rhTNF-α 25 µg/m² + Caelyx 30 mg/m², rhTNF-α 25 µg/m² + Caelyx 40 mg/m², rhTNF-α 250 µg/m² + Caelyx 40 mg/m², rhTNF-α 50 µg/m² + Caelyx 40 mg/m² |
| Recombinant human TNF-αAlso: BeromunRecombinant 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. | Drug | rhTNF-α 100 µg/m² + Caelyx 40 mg/m², rhTNF-α 150 µg/m² + Caelyx 40 mg/m², rhTNF-α 200 µg/m² + Caelyx 40 mg/m², rhTNF-α 25 µg/m² + Caelyx 30 mg/m², rhTNF-α 25 µg/m² + Caelyx 40 mg/m², rhTNF-α 250 µg/m² + Caelyx 40 mg/m², rhTNF-α 50 µg/m² + Caelyx 40 mg/m² |
Primary outcome
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
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: * Grade 3 toxicities that recover to grade 1 or less within 48 hours after standard supportive treatment. * Grade 4 neutropenia that recovers within 14 days. * Grade 4 thrombocytopenia that recovers within 14 days. * Grade 4 anemia that recovers within 14 days.
2 secondary outcomes
Overall tumor response using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Time frame: 4 weeks
Caelyx/doxorubicin plasma levels
Time frame: 0, 24, 48 and 192 hours post-dose
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elke Jäger, MD principal investigator
Krankenhaus Nordwest, Frankfurt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Recombinant human TNF-α, Liposomal doxorubicin and Caelyx in people with Solid Tumors and Lymphomas, run by Ludwig Institute for Cancer Research at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 16 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2015.