NeoplasmsPhase 1NCT01259518
Dose Escalation Study of TriN2755 in Advanced Solid Tumors and Sarcomas
A Phase 1 study testing TRIN2755 in people with Neoplasms, run by Trin Therapeutics GmbH at 1 site in Germany.
Trial summary
This is an open-label, parallel-group, two-center, safety, activity and pharmacokinetic study of TriN 2755 given at increasing dose levels as intravenous infusions administered over 4 hours. The study is divided into two parts: Part I a dose escalation phase and Part II an extension phase. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- TRIN2755
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteGermany
- Study dates
- Nov 2009to Jan 2012
- 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
- Male or female patients of age > 18 years
- Patients with a histologically / cytologically confirmed diagnosis of advanced solid tumor or sarcoma for which a treatment of proven efficacy does not exist or an established treatment(s) had failed
- Measurable or non-measurable disease according to RECIST v1.0 criteria. Patients should have at least one measurable lesion or disease which is non-measurable but can clearly be evaluated for response
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- Life expectancy of at least 3 months
- Ability to understand the nature of the study and willingness to sign a written informed consent document
- Willingness and ability to comply with the study protocol for the duration of the study
Who cannot join
- Any lymphoma or other hematological tumors
- Known brain metastases
- Earlier history of other tumors, except non melanoma-skin cancer or in situ cervical carcinoma curatively excised
- Major surgery within 4 weeks prior to treatment start
- Extensive radiotherapy, within 2 weeks of treatment start, or cytotoxic chemotherapy or limited radiotherapy within 2 weeks of treatment start
- Unresolved toxicity from prior chemotherapy (including approved and experimental drugs)
Show all 34Show fewer
- Any of the following abnormal baseline hematological values:
- Hb < 10g/dl,
- WBC < 3.0 x 109/l Neutrophils < 1.5 x 109/l
- Platelets < 100 x 109/l
- Any of the following abnormal baseline liver function tests:
- Serum bilirubin > 1.5 x upper normal limit, > 3 x if due to tumor
- ALAT and/or ASAT > 2.5 x upper normal limit, > 5 x if due to tumor
- The following abnormal baseline renal function test:
- Serum creatinine > 1.5 mg/dl
- Creatinine clearance < 50 ml/min
- All clinically relevant cardiovascular abnormalities (i.e. myocardial infarction within the prior 6 months, cardiac arrhythmia requiring medication, uncontrolled hypertension, abnormal cardiac function (* class II of NYHA classification), cardiac failure or non compensated active heart disease (* class II of NYHA classification)
- Neurologic: symptomatic motor or sensory neurotoxicity grade 2 NCI CTC
- Primary tumor associated with central nervous system-related symptoms interfering with the informed consent or with the study
- History of psychiatric disabilities, seizures or central nervous system disorders, which is considered to be clinically significant by the investigator and could interfere with informed consent or adequate follow-up
- Major fluid effusions (e.g. ascites, pleural effusion), or clinically relevant blood loss
- Interstitial pneumonia or lung fibrosis
- History or presence of thromboses or clotting disorders
- Concomitant medication for non-vital indications with known hepatotoxic or nephrotoxic potential (e.g, aminoglycoside antibiotics)
- Serious (Grade 3-4) uncontrolled intercurrent infections
- Any history of alcohol abuse or drug addiction
- Positive results of virus serology tests (i.e. detection of HBsAg and antibodies to HCV, HIV1, HIV2, CMV and EBV)
- Clinical conditions equal to protocol definitions of DLT
- Participation in any investigational drug study within 30 days preceding treatment start
- Male or pre-menopause female patients unable to practice a medically approved method of contraception during the study and the 3-month period thereafter (all patients potentially fertile)
- Pregnancy or breast feeding women
- Any condition which in the judgment of the investigator would place the subject at undue risk or interfere with the results of the study (e.g. increased medical risks due to non malignant organ or systemic disease or secondary effects of cancer)
- History of allergic reactions attributed to compounds of the same chemical class (dacarbazine, temozolomide) as TriN 2755 or any excipients of IMP
- Mental handicap or legal incapacity
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Department of Internal Medicine West German Cancer Centre University Hospital Essen
Essen, 45122
Max E Scheulen, PHD/MD, +49 201 723 ext. 3152, cordula.derks@uk-essen.de
Max E Scheulen, PHD/MD
About this study
Official title: A Phase I Dose Escalation Study on the Tolerability and Activity of TriN 2755 in Patients With Advanced Solid Tumors and Sarcomas Using Two Different Dosage Regimens
This is an open-label, parallel-group, two-center, safety, activity and pharmacokinetic study of TriN 2755 given at increasing dose levels as intravenous infusions administered over 4 hours. The study is divided into two parts: Part I a dose escalation phase and Part II an extension phase.
Read the detailed description
Classical chemotherapeutic agents include the class of alkylating agents with covalent modification of biopolymers and in particular, bases of DNA, as proposed mechanism of cytotoxic action. Bifunctional alkylating agents, which yield inter- or intrastrand cross-links include nitrogen mustards, mitomycin C and platinum complexes. In contrast, monofunctional alkylating agents act by reacting with single electron-rich sites in bases of DNA strands. The most prominent class of the latter group is the triazene, which is based on nitrogen-rich chemistry. It is generally accepted that triazenes, upon metabolic activation via N demethylation, yield highly reactive carbocations, which covalently bind to biopolymers. The novel triazene TriN 2755 differs from other triazenes through its physicochemical properties such as high hydrophilicity and photostability, and in particular by its potent, dose dependent antitumor activity in a spectrum of cancers including dacarbazine-resistant tumors, where treatment options for metastatic disease are still not satisfactory and medical needs exist.
This is an open-label, parallel-group, two-center, safety, activity and pharmacokinetic study of TriN 2755 given at increasing dose levels as intravenous infusions administered over 4 hours. The study is divided into two parts: Part I a dose escalation phase and Part II an extension phase.
Part I of the Study (Dose Escalation Phase):
In the first part of the study, two treatment schedules will be investigated in parallel:
Treatment schedule A: The study medication will be infused once every 28 days in a 4-week cycle (Group A) Treatment schedule B: The study medication will be infused once every 7 days in a 4-week cycle (Group B)
In treatment schedule A (Group A), the planned starting dose to be investigated is 25 mg TriN 2755 given once followed by a recovery period of 4 weeks. Subsequent patients can only be included on a new dose level when the safety review from all patients included at the preceding dose level(s) at Day 28 after infusion (end of Cycle 1) does not indicate relevant toxicity.
In treatment schedule B (Group B), the planned starting dose to be investigated is 800mg, given once every 7 days in a 4 week cycle. Subsequent patients can only be included on a new dose level when the safety review from all patients included at the preceding dose level(s) at Day 28 after the start of the first infusion (end of Cycle 1) does not indicate relevant toxicity.
Plasma samples to evaluate the pharmacokinetics of TriN 2755 are collected at predefined schedules after the first administration at each dose level and at pre-dose and at expected peak times during the subsequent administrations within the first treatment cycle only (Group B). Urine samples are collected over 24 hours after the first administration at each dose level within the first treatment cycle only.
Once the MTD is reached, two expanded cohorts of patients are treated with the Maximum Recommended Dose (MRD) which is one dose level below the MTD or at lower dose levels, if indicated. This second part of the study (expansion) allows for enrolment of approximately additional 9 patients per treatment schedule, at the chosen dose, in order to better assess the safety and possible antitumor activity of TriN 2755. The exact number of patients to be enrolled in this expanded phase is decided by a Monitoring Board. The patients are treated at or near the planned phase II dose, without expanding or prolonging the study excessively.
- Conditions
- Neoplasms
- Being tested
- TRIN2755
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRIN2755Drug
In treatment schedule A (Group A), the planned starting dose to be investigated is 25 mg TriN 2755 given once followed by a recovery period of 4 weeks. Subsequent patients can only be included on a new dose level when the safety review from all patients included at the preceding dose level(s) at Day 28 after infusion (end of Cycle 1) does not indicate relevant toxicity.
TRIN2755Drug
In treatment schedule B (Group B), the starting dose to be investigated is 800mg, given once every 7 days in a 4 week cycle. Subsequent patients can only be included on a new dose level when the safety review from all patients included at the preceding dose level(s) at Day 28 after the start of the first infusion (end of Cycle 1) does not indicate relevant toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Once monthly administration of TRIN2755 | Experimental | Not described Receives: Drug: TRIN2755 |
| Once weekly administration of TRIN2755 | Experimental | Not described Receives: Drug: TRIN2755 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Measured: at baseline and beginning of every cycle
Secondary outcomes (5)
Objective response rate (ORR); RECIST v1.0 Criteria
Measured: 3 Years
Progression free survival (PFS)
Measured: 3 years
Overall survival (OS) within 12 months after the first infusion of TriN 2755
Measured: 12 months
Pharmacokinetics of TRIN2755 and its metabolites
TriN 2755 and a selection of assumed metabolites in plasma and urine samples will be analyzed by using a validated Reverse-Phase High Performance Liquid Chromatography (RV-HPLC) procedure with Mass Spectrometric (MS) detection of e.g. area únder curve(AUC) , Concentration maximum (Cmax)
Measured: 4 weeks
Concentration of DNA methyl adducts in leucocytes and urine, analysis of DNA strand breaks
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2010 (estimated)
- Study startNov 2009
- Primary completionSep 2011 (estimated)
- Study completionJan 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Trin Therapeutics GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University Hospital, Essen, Central European Society for Anticancer Drug Research, Assign Data Management and Biostatistics GmbH
- Investigators
- Max E Scheulen, PHD MD, Principal investigator, Department of Internal Medicine West German Cancer Centre University Hospital Essen Essen, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01259518
- Sponsor's protocol ID
- TRIN2755-I-01
- Status last verified
- Jun 2011
- First submitted
- 24 Nov 2010
- Last updated
- 8 Jun 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study on the Tolerability and Activity of TriN 2755 in Patients With Advanced Solid Tumors and Sarcomas Using Two Different Dosage Regimens
- ClinicalTrials.gov ID
- NCT01259518
- Acronym / sponsor ID
- TRIN2755-I-01
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Trin Therapeutics GmbHIndustry (pharma, biotech, devices)
- Collaborators
- University Hospital, Essen, Central European Society for Anticancer Drug Research, Assign Data Management and Biostatistics GmbH
- Study start
- Nov 2009
- Primary completion
- Sep 2011 (estimated)
- Study completion
- Jan 2012 (estimated)
- First posted
- 14 Dec 2010 (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.
This is an open-label, parallel-group, two-center, safety, activity and pharmacokinetic study of TriN 2755 given at increasing dose levels as intravenous infusions administered over 4 hours. The study is divided into two parts: Part I a dose escalation phase and Part II an extension phase.
Detailed description
Classical chemotherapeutic agents include the class of alkylating agents with covalent modification of biopolymers and in particular, bases of DNA, as proposed mechanism of cytotoxic action. Bifunctional alkylating agents, which yield inter- or intrastrand cross-links include nitrogen mustards, mitomycin C and platinum complexes. In contrast, monofunctional alkylating agents act by reacting with single electron-rich sites in bases of DNA strands. The most prominent class of the latter group is the triazene, which is based on nitrogen-rich chemistry. It is generally accepted that triazenes, upon metabolic activation via N demethylation, yield highly reactive carbocations, which covalently bind to biopolymers. The novel triazene TriN 2755 differs from other triazenes through its physicochemical properties such as high hydrophilicity and photostability, and in particular by its potent, dose dependent antitumor activity in a spectrum of cancers including dacarbazine-resistant tumors, where treatment options for metastatic disease are still not satisfactory and medical needs exist.
This is an open-label, parallel-group, two-center, safety, activity and pharmacokinetic study of TriN 2755 given at increasing dose levels as intravenous infusions administered over 4 hours. The study is divided into two parts: Part I a dose escalation phase and Part II an extension phase.
Part I of the Study (Dose Escalation Phase):
In the first part of the study, two treatment schedules will be investigated in parallel:
Treatment schedule A: The study medication will be infused once every 28 days in a 4-week cycle (Group A) Treatment schedule B: The study medication will be infused once every 7 days in a 4-week cycle (Group B)
In treatment schedule A (Group A), the planned starting dose to be investigated is 25 mg TriN 2755 given once followed by a recovery period of 4 weeks. Subsequent patients can only be included on a new dose level when the safety review from all patients included at the preceding dose level(s) at Day 28 after infusion (end of Cycle 1) does not indicate relevant toxicity.
In treatment schedule B (Group B), the planned starting dose to be investigated is 800mg, given once every 7 days in a 4 week cycle. Subsequent patients can only be included on a new dose level when the safety review from all patients included at the preceding dose level(s) at Day 28 after the start of the first infusion (end of Cycle 1) does not indicate relevant toxicity.
Plasma samples to evaluate the pharmacokinetics of TriN 2755 are collected at predefined schedules after the first administration at each dose level and at pre-dose and at expected peak times during the subsequent administrations within the first treatment cycle only (Group B). Urine samples are collected over 24 hours after the first administration at each dose level within the first treatment cycle only.
Once the MTD is reached, two expanded cohorts of patients are treated with the Maximum Recommended Dose (MRD) which is one dose level below the MTD or at lower dose levels, if indicated. This second part of the study (expansion) allows for enrolment of approximately additional 9 patients per treatment schedule, at the chosen dose, in order to better assess the safety and possible antitumor activity of TriN 2755. The exact number of patients to be enrolled in this expanded phase is decided by a Monitoring Board. The patients are treated at or near the planned phase II dose, without expanding or prolonging the study excessively.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Once monthly administration of TRIN2755 | Experimental | Drug: TRIN2755 |
| Once weekly administration of TRIN2755 | Experimental | Drug: TRIN2755 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female patients of age > 18 years
- Patients with a histologically / cytologically confirmed diagnosis of advanced solid tumor or sarcoma for which a treatment of proven efficacy does not exist or an established treatment(s) had failed
- Measurable or non-measurable disease according to RECIST v1.0 criteria. Patients should have at least one measurable lesion or disease which is non-measurable but can clearly be evaluated for response
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- Life expectancy of at least 3 months
Key exclusion criteria (34 listed)
- Any lymphoma or other hematological tumors
- Known brain metastases
- Earlier history of other tumors, except non melanoma-skin cancer or in situ cervical carcinoma curatively excised
- Major surgery within 4 weeks prior to treatment start
- Extensive radiotherapy, within 2 weeks of treatment start, or cytotoxic chemotherapy or limited radiotherapy within 2 weeks of treatment start
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 |
|---|---|---|
| TRIN2755In treatment schedule A (Group A), the planned starting dose to be investigated is 25 mg TriN 2755 given once followed by a recovery period of 4 weeks. Subsequent patients can only be included on a new dose level when the safety review from all patients included at the preceding dose level(s) at Day 28 after infusion (end of Cycle 1) does not indicate relevant toxicity. | Drug | Once monthly administration of TRIN2755 |
| TRIN2755In treatment schedule B (Group B), the starting dose to be investigated is 800mg, given once every 7 days in a 4 week cycle. Subsequent patients can only be included on a new dose level when the safety review from all patients included at the preceding dose level(s) at Day 28 after the start of the first infusion (end of Cycle 1) does not indicate relevant toxicity. | Drug | Once weekly administration of TRIN2755 |
Primary outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: at baseline and beginning of every cycle
5 secondary outcomes
Objective response rate (ORR); RECIST v1.0 Criteria
Time frame: 3 Years
Progression free survival (PFS)
Time frame: 3 years
Overall survival (OS) within 12 months after the first infusion of TriN 2755
Time frame: 12 months
Pharmacokinetics of TRIN2755 and its metabolites
Time frame: 4 weeks
Concentration of DNA methyl adducts in leucocytes and urine, analysis of DNA strand breaks
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2011.
Related trials for Neoplasms
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
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.
Max E Scheulen, PHD MD principal investigator
Department of Internal Medicine West German Cancer Centre University Hospital Essen Essen, 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 TRIN2755 in people with Neoplasms, run by Trin Therapeutics GmbH 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 7 inclusion and 34 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: status not confirmed, as of the sponsor's last update on 8 Jun 2011. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Max E. Scheulen, PhD/MD (+49 201 723 ext. 3152, cordula.derks@uk-essen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events as a Measure of Safety and Tolerability (time frame: at baseline and beginning of every cycle). 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 8 Jun 2011.