Solid TumorPhase 1NCT00697879
Safety Study of the Histone Deacetylase Inhibitor, CHR-3996, in Patients With Advanced Solid Tumours
A Phase 1 study testing CHR-3996 in people with Solid Tumor, run by Chroma Therapeutics at 3 sites in 2 countries.
Trial summary
CHR-3996 is one of a new class of anti-cancer agents - histone deacetylase inhibitors (HDACi) - that has exhibited pleiotropic activity both in vitro and in vivo against a range of human cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- CHR-3996
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Feb 2008to Nov 2011
- 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
- Signed, informed consent
- Histologically or cytologically confirmed malignant solid tumour refractory to standard therapy or for which no standard therapy exists
- Recovered from all acute adverse effects of prior therapies (excluding alopecia and grade 1 neuropathy)
- Adequate bone marrow, hepatic and renal function including the following
- Hb ≥ 9.0 g/dL, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥100 x 109/L
- Total bilirubin ≤ 1.5 x upper normal limit, excluding cases where elevated bilirubin can be attributed to Gilberts Syndrome
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- AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit (or 5x UNL in the presence of liver metastases)
- Creatinine ≤ 1.5 x upper normal limit
- Age ≥ 18 years
- Performance status (PS) ≤ 2 (ECOG scale)
- Estimated life expectancy greater than 3 months
- Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to start of trial. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception include IUD, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge)
Who cannot join
- Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial entry (or a longer period depending on the defined characteristics of the agents used e.g. 6 weeks for mitomycin or nitrosourea, 3 months for antibodies). In patients with progressive disease, continuation of LHRH agonists for prostate cancer, bisphosphonates for bone disease and corticosteroids are permitted provided the dose does not change during the trial
- Patients with a prior allogeneic haematopoietic stem cell transplant
- Co-existing active infection or serious concurrent illness
- Patients with significant cardiovascular disease as defined by:
- history of congestive heart failure requiring therapy
- history of angina pectoris requiring treatment or myocardial infarction within 6 months prior to trial entry
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- presence of severe valvular heart disease
- presence of an atrial or ventricular arrhythmia requiring treatment
- LVEF below the normal range at the study centre
- Uncontrolled hypertension
- A history of QTc abnormalities or with a mean QTc interval >450 msec at screening
- Any medical or other condition that in the investigator's opinion renders the patient unsuitable for this study due to unacceptable risk
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
- Gastrointestinal disorders that may interfere with absorption of the study drug.
- Patients with known brain tumours or metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- More than 6 prior chemotherapy regimens
- Patients requiring growth factor support (erythropoietin, G(M)CSF, etc)
- Patients requiring palliative radiotherapy within the last 4 weeks prior to study entry
- Uncontrolled hypercalcaemia (>CTCAE v3 grade I)
- Abnormal plasma potassium or magnesium levels (CTCAE v3 grade 3 or greater) despite therapy
- Pregnant or breast-feeding women
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Netherlands2 sites
Erasmus MC University Medical Center - Location Centrum
Rotterdam, 3015 CE
Erasmus University Medical Center - Location Daniel den Hoed
Rotterdam, 3075 EA
United Kingdom1 site
The Royal Marsden Hospital
Sutton, Surrey, SM2 5PT
About this study
Official title: A Phase I Study to Evaluate the Safety and Tolerability of the Histone Deacetylase Inhibitor, CHR-3996, in Patients With Advanced Solid Tumours
CHR-3996 is one of a new class of anti-cancer agents - histone deacetylase inhibitors (HDACi) - that has exhibited pleiotropic activity both in vitro and in vivo against a range of human cancer cells. Regulation of the acetylation of both histone and non-histone proteins by histone deacetylase enzymes is one of the key mechanisms involved in epigenetic control of gene expression. HDACi have demonstrated activity in both in vitro cytotoxicity, and in vivo tumour xenograft studies
- Conditions
- Solid Tumor
- Being tested
- CHR-3996
- Keywords
- tumour, Solid tumour, histone deacetylase inhibitor, dose escalation, cancer
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHR-3996Drug
Also called Histone deacetylase inhibitor, HDACi
Once daily oral ingestion of capsules (5, 10, 20 or 40 mg), dose depending on cohort, treatment cycle of 28 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Oral, once daily administration of CHR-3996 to determine safety and tolerability Receives: Drug: CHR-3996 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety, tolerability, dose-limiting toxicities (DLT), maximum acceptable dose (MAD) and maximum tolerated dose (MTD) of CHR-3996 when administered orally to patients with advanced or treatment refractory solid tumours
Measured: After 28 days treatment
Secondary outcomes (2)
To determine pharmacokinetic parameters of CHR-3996
Measured: After 1 and 28 days treatment
To perform a preliminary assessment of the anti-tumour activity of CHR-3996
Measured: During treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2008 (estimated)
- Study startFeb 2008
- Primary completionNov 2010
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chroma Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- F ALM Eskens, Dr, Principal investigator, Erasmus MC University Medical CenterUdai Banerji, Dr, Principal investigator, The Royal Marsden Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00697879
- Sponsor's protocol ID
- CHR-3996-001
- Other IDs
- EudraCT Number: 2007-005043-19
- Status last verified
- Nov 2011
- First submitted
- 10 Jun 2008
- Last updated
- 28 Nov 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Evaluate the Safety and Tolerability of the Histone Deacetylase Inhibitor, CHR-3996, in Patients With Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT00697879
- Acronym / sponsor ID
- CHR-3996-001
- Conditions
- Solid Tumor
- Keywords
- tumour, Solid tumour, histone deacetylase inhibitor, dose escalation, cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Chroma TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Feb 2008
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 16 Jun 2008 (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.
CHR-3996 is one of a new class of anti-cancer agents - histone deacetylase inhibitors (HDACi) - that has exhibited pleiotropic activity both in vitro and in vivo against a range of human cancer cells. Regulation of the acetylation of both histone and non-histone proteins by histone deacetylase enzymes is one of the key mechanisms involved in epigenetic control of gene expression. HDACi have demonstrated activity in both in vitro cytotoxicity, and in vivo tumour xenograft studies
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: CHR-3996Oral, once daily administration of CHR-3996 to determine safety and tolerability |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Signed, informed consent
- Histologically or cytologically confirmed malignant solid tumour refractory to standard therapy or for which no standard therapy exists
- Recovered from all acute adverse effects of prior therapies (excluding alopecia and grade 1 neuropathy)
- Adequate bone marrow, hepatic and renal function including the following
- Age ≥ 18 years
Key exclusion criteria (21 listed)
- Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial entry (or a longer period depending on the defined characteristics of the agents used e.g. 6 weeks for mitomycin or nitrosourea, 3 months for antibodies). In patients with progressive disease, continuation of LHRH agonists for prostate cancer, bisphosphonates for bone disease and corticosteroids are permitted provided the dose does not change during the trial
- Patients with a prior allogeneic haematopoietic stem cell transplant
- Co-existing active infection or serious concurrent illness
- Patients with significant cardiovascular disease as defined by:
- Any medical or other condition that in the investigator's opinion renders the patient unsuitable for this study due to unacceptable risk
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 |
|---|---|---|
| CHR-3996Also: Histone deacetylase inhibitor, HDACiOnce daily oral ingestion of capsules (5, 10, 20 or 40 mg), dose depending on cohort, treatment cycle of 28 days | Drug | 1 |
Primary outcome
To determine the safety, tolerability, dose-limiting toxicities (DLT), maximum acceptable dose (MAD) and maximum tolerated dose (MTD) of CHR-3996 when administered orally to patients with advanced or treatment refractory solid tumours
Time frame: After 28 days treatment
2 secondary outcomes
To determine pharmacokinetic parameters of CHR-3996
Time frame: After 1 and 28 days treatment
To perform a preliminary assessment of the anti-tumour activity of CHR-3996
Time frame: During treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2011.
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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.
F ALM Eskens, Dr principal investigator
Erasmus MC University Medical Center
Udai Banerji, Dr principal investigator
The Royal Marsden Hospital
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CHR-3996 in people with Solid Tumor, run by Chroma Therapeutics at 3 sites in 2 countries.
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 12 inclusion and 21 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: finished, as of the sponsor's last update on 28 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands, United Kingdom. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the safety, tolerability, dose-limiting toxicities (DLT), maximum acceptable dose (MAD) and maximum tolerated dose (MTD) of CHR-3996 when administered orally to patients with advanced or treatment refractory solid tumours (time frame: After 28 days treatment). 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 28 Nov 2011.