Breast CancerPhase 1NCT00511576
Study to Evaluate Combination Treatment of MGCD0103 and Docetaxel (Taxotere®) for Subjects With Advanced Cancer Tumors
A Phase 1 study testing MGCD0103 & Docetaxel in people with Breast Cancer and Lung Cancer, run by Mirati Therapeutics Inc. at 2 sites in United States.
Trial summary
The purpose of this study is to test the combination of an experimental drug known as MGCD0103 given along with an FDA-approved drug called docetaxel. This is a Phase 1 study that will look at different doses of MGCD0103 given along with docetaxel in order to better understand the effects (positive and negative) of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Lung Cancer, Pulmonary Cancer
- What is being tested?
- MGCD0103 & Docetaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2007to Mar 2009
- 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
- Subjects must meet ALL inclusion criteria to be enrolled in the study
- Age ≥18 years.
- Diagnosis of malignant solid tumor (histologically or cytologically confirmed) where treatment with docetaxel is considered standard of care, or advanced solid malignancy that has failed to respond to standard therapy, or has progressed despite standard therapy, or where there is no reasonable likelihood of achieving clinical benefit with existing therapies.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- Adequate organ function, including: Hemoglobin (Hgb) ≥8.0g/dL; Absolute neutrophil count (ANC) ≥1.5 x 10<9>/L (≥1500/mm<3>); Platelets ≥100 x 10<9>/L (≥100,000/mm<3>); Total bilirubin ≤1.5 x ULN (upper limit of normal); AST (SGOT) and ALT (SGPT) ≤2.5 x ULN; Alkaline phosphatase ≤5.0 x ULN; Serum creatinine ≤2.0 x ULN.
- Evidence of measurable disease (ie, at least one lesion that can accurately be measured in at least one dimension as ≥20 mm with conventional techniques or ≥10 mm with spiral CT scan). The requirement for measurable disease will not apply to subjects with prostate cancer.
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- A minimum of 4 weeks elapsed since any major surgery.
- At least 4 weeks elapsed since any prior anticancer therapy (standard or investigational) and full recovery (NCI CTCAE grade 1) from the toxic effects of that treatment. Antiandrogen therapy is permitted for subjects with prostate cancer.
- For women of childbearing potential, a negative serum pregnancy test within 10 days of treatment, and use of physician-approved methods of birth control throughout the study.
- Written, informed consent, willingness, and ability to comply with all study procedures.
Who cannot join
- Subjects meeting any of the following criteria will not be included in the study.
- Prior taxane and HDAC inhibitor combination therapy.
- Previous or concurrent malignancy except adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
- Clinically significant cardiac disease including congestive heart failure (New York Heart Association Class III or IV), including pre-existing ventricular arrhythmia or conduction abnormality requiring medication, or cardiomyopathy.
- Active and uncontrolled clinically significant infection.
- History of melena, hematemesis, or hemoptysis within the last 3 months.
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- Known central nervous system metastases controlled ≤3 months.
- Pregnant or lactating women. Women of child-bearing potential must have a negative serum pregnancy test within 10 days of starting study drug on Day 1 Cycle 1.
- Known hypersensitivity to taxanes, HDAC inhibitors, and/or any components of MGCD0103 capsules or docetaxel formulation components (eg, polysorbate 80).
- Known HIV or known active Hepatitis B or C.
- Presence of serious illness, medical condition, or other medical history, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
- Any condition that will put the subject at undue risk or discomfort as a result of adherence to study procedures (eg, requirement to take MGCD0103 with a low pH beverage).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase 1, Open-Label, Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of MGCD0103 (MG-0103) in Combination With Docetaxel (Taxotere®) in Subjects With Advanced Solid Malignancies
The purpose of this study is to test the combination of an experimental drug known as MGCD0103 given along with an FDA-approved drug called docetaxel. This is a Phase 1 study that will look at different doses of MGCD0103 given along with docetaxel in order to better understand the effects (positive and negative) of this combination on the subject's body and disease.
The study would like to find the following information:
- How long MGCD0103 and docetaxel stay in the subject's body;
- What effects, good and/or bad, MGCD0103 and docetaxel have on the subject and on his/her cancer; and
- If the genetic and chemical make-up of the subject's blood cells and tumor cells play a role in how you respond or do not respond to MGCD0103 and docetaxel.
Read the detailed description
This Phase 1 study will evaluate escalating doses of orally administered MGCD0103 in combination with two fixed doses (60 mg/m2 and 75 mg/m2) of IV docetaxel. In the US, docetaxel is recommended at these or even higher doses (up to 100 mg/m2), both as a single agent or in combination with other cytotoxic drugs (e.g., cisplatin, doxorubicin, cyclophosphamide, and 5-fluorouracil), for the treatment of NSCLC, prostate cancer, gastric adenocarcinoma, and head and neck cancer. In Japan, 60 mg/m2 IV docetaxel is the approved dose for the treatment of breast cancer.
MGCD0103 belongs to the class of more selective, less globally cytotoxic agents being investigated for treatment of cancers today, and may offer a lesser and/or non-overlapping toxicity profile than the cytotoxic agents with which docetaxel is currently combined. MGCD0103 doses ranging from 50 to 135 mg have been administered in combination with the approved regimen of azacitidine (Vidaza®) (75 mg/m2/day for 5 days every 4 weeks) to patients with high-risk MDS and AML. A 50 mg dose of MGCD0103 has been administered in combination with the approved regimen of gemcitabine (1000 mg/m2 once weekly for 3 consecutive weeks of each 4-week cycle) to patients with advanced solid tumors; higher doses of MGCD0103 will soon be evaluated in that trial.
Given the above, the proposed starting dose of 60 mg/m2 IV docetaxel and 50 mg MGCD0103 is considered appropriately safe for initial investigation of this combination. Based on the results observed in Part 1, the study may also evaluate 75 mg/m2 IV docetaxel and escalating doses of orally administered MGCD0103 in Part 2 in order to determine whether this dosing regimen is safe and would also warrant further investigation.
- Conditions
- Breast Cancer, Lung Cancer, Pulmonary Cancer, Non-Small-Cell Lung Carcinoma, Prostate Cancer, Prostatic Cancer
- Being tested
- MGCD0103 & Docetaxel
- Keywords
- Advanced or Metastatic Breast Cancer, Breast Cancer, Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC), Hormone Refractory Prostate Cancer, Prostate Cancer, Gastric Cancer, Advanced Gastric Adenocarcinoma, HDAC Inhibitor, Taxotere, Docetaxel
- Medical subject headings
- Breast Neoplasms, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Prostatic Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MGCD0103 & DocetaxelDrug
Also called MG-0103, Taxotere®
In both Parts 1 and 2, subsequent doses of MGCD0103 will be escalated in 25 mg increments until the MTD of MGCD0103 in combination with each fixed dose (60 mg/m2 or 75 mg/m2) ofIV docetaxel is determined.
In both parts 1 and 2, MGCD0103 will be administered orally TIW for 3 weeks beginning on Day 1 at 1 hour prior to the start of the IV docetaxel infusion.
There will be no scheduled break between cycles and no limit to the number of cycles a subject can receive provided they do not have disease progression as defined by RECIST, or a clinically significant drug-related adverse event (AE) that does not resolve or respond to treatment intervention with 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Active comparator | In Part 1, cohorts of three to six subjects will receive doses of MGCD0103 administered orally three times per week (TIW) in combination with 60 mg/m2 IV docetaxel administered as a 1-hour infusion on Day 1 of each 3-week (21-day) cycle. The starting dose of MGCD0103 in Part 1 will be 50 mg (approximately 25 mg/m2). Receives: Drug: MGCD0103 & Docetaxel |
| Part 2 | Active comparator | Part 2 will begin once the MTD for MGCD0103 in combination with 60 mg/m2 IV docetaxel has been determined and further evaluated in the expansion phase. In Part 2, cohorts of three to six subjects will receive escalating doses of MGCD0103 administered orally TIW in combination with 75 mg/m2 docetaxel administered as a 1-hour IV infusion on Day 1 of each cycle. The starting dose of MGCD0103 administered in combination with 75 mg/m2 IV docetaxel will be the MTD from Part 1 minus 25 mg. Receives: Drug: MGCD0103 & Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and safety profile of escalating doses of orally administered MGCD0103 in combination with two fixed doses (60 mg/m2 and 75 mg/m2) of IV docetaxel.
Measured: 15 months
To assess the plasma pharmacokinetics (PK) of MGCD0103 (and/or its metabolites) and IV docetaxel administered in combination.
Measured: 15 months
To evaluate potential pharmacodynamic (PD) effects of orally administered MGCD0103 in combination with IV docetaxel.
Measured: 15 months
To determine the overall tumor response of orally administered MGCD0103 in combination with IV docetaxel according to Response Evaluation Criteria in Solid Tumors (RECIST) methodology.
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionMar 2009
- Study completionMar 2009
Why it stopped: Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 will be closed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies 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
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mirati Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Gregory Reid, MSc, MBA, Study director, MethylGene Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00511576
- Sponsor's protocol ID
- 103 PH US 2007 CL001
- Status last verified
- Jan 2015
- First submitted
- 3 Aug 2007
- Last updated
- 8 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of MGCD0103 (MG-0103) in Combination With Docetaxel (Taxotere®) in Subjects With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT00511576
- Acronym / sponsor ID
- 103 PH US 2007 CL001
- Conditions
- Breast Cancer, Lung Cancer, Pulmonary Cancer, Non-Small-Cell Lung Carcinoma, Prostate Cancer, Prostatic Cancer
- Keywords
- Advanced or Metastatic Breast Cancer, Breast Cancer, Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC), Hormone Refractory Prostate Cancer, Prostate Cancer, Gastric Cancer, Advanced Gastric Adenocarcinoma, HDAC Inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 will be closed.
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Mirati Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2007
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 6 Aug 2007 (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.
The purpose of this study is to test the combination of an experimental drug known as MGCD0103 given along with an FDA-approved drug called docetaxel. This is a Phase 1 study that will look at different doses of MGCD0103 given along with docetaxel in order to better understand the effects (positive and negative) of this combination on the subject's body and disease.
The study would like to find the following information:
- How long MGCD0103 and docetaxel stay in the subject's body;
- What effects, good and/or bad, MGCD0103 and docetaxel have on the subject and on his/her cancer; and
- If the genetic and chemical make-up of the subject's blood cells and tumor cells play a role in how you respond or do not respond to MGCD0103 and docetaxel.
Detailed description
This Phase 1 study will evaluate escalating doses of orally administered MGCD0103 in combination with two fixed doses (60 mg/m2 and 75 mg/m2) of IV docetaxel. In the US, docetaxel is recommended at these or even higher doses (up to 100 mg/m2), both as a single agent or in combination with other cytotoxic drugs (e.g., cisplatin, doxorubicin, cyclophosphamide, and 5-fluorouracil), for the treatment of NSCLC, prostate cancer, gastric adenocarcinoma, and head and neck cancer. In Japan, 60 mg/m2 IV docetaxel is the approved dose for the treatment of breast cancer.
MGCD0103 belongs to the class of more selective, less globally cytotoxic agents being investigated for treatment of cancers today, and may offer a lesser and/or non-overlapping toxicity profile than the cytotoxic agents with which docetaxel is currently combined. MGCD0103 doses ranging from 50 to 135 mg have been administered in combination with the approved regimen of azacitidine (Vidaza®) (75 mg/m2/day for 5 days every 4 weeks) to patients with high-risk MDS and AML. A 50 mg dose of MGCD0103 has been administered in combination with the approved regimen of gemcitabine (1000 mg/m2 once weekly for 3 consecutive weeks of each 4-week cycle) to patients with advanced solid tumors; higher doses of MGCD0103 will soon be evaluated in that trial.
Given the above, the proposed starting dose of 60 mg/m2 IV docetaxel and 50 mg MGCD0103 is considered appropriately safe for initial investigation of this combination. Based on the results observed in Part 1, the study may also evaluate 75 mg/m2 IV docetaxel and escalating doses of orally administered MGCD0103 in Part 2 in order to determine whether this dosing regimen is safe and would also warrant further investigation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Active comparator | Drug: MGCD0103 & DocetaxelIn Part 1, cohorts of three to six subjects will receive doses of MGCD0103 administered orally three times per week (TIW) in combination with 60 mg/m2 IV docetaxel administered as a 1-hour infusion on Day 1 of each 3-week (21-day) cycle. The starting dose of MGCD0103 in Part 1 will be 50 mg (approximately 25 mg/m2). |
| Part 2 | Active comparator | Drug: MGCD0103 & DocetaxelPart 2 will begin once the MTD for MGCD0103 in combination with 60 mg/m2 IV docetaxel has been determined and further evaluated in the expansion phase. In Part 2, cohorts of three to six subjects will receive escalating doses of MGCD0103 administered orally TIW in combination with 75 mg/m2 docetaxel administered as a 1-hour IV infusion on Day 1 of each cycle. The starting dose of MGCD0103 administered in combination with 75 mg/m2 IV docetaxel will be the MTD from Part 1 minus 25 mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Subjects must meet ALL inclusion criteria to be enrolled in the study
- Age ≥18 years.
- Diagnosis of malignant solid tumor (histologically or cytologically confirmed) where treatment with docetaxel is considered standard of care, or advanced solid malignancy that has failed to respond to standard therapy, or has progressed despite standard therapy, or where there is no reasonable likelihood of achieving clinical benefit with existing therapies.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- Adequate organ function, including: Hemoglobin (Hgb) ≥8.0g/dL; Absolute neutrophil count (ANC) ≥1.5 x 10<9>/L (≥1500/mm<3>); Platelets ≥100 x 10<9>/L (≥100,000/mm<3>); Total bilirubin ≤1.5 x ULN (upper limit of normal); AST (SGOT) and ALT (SGPT) ≤2.5 x ULN; Alkaline phosphatase ≤5.0 x ULN; Serum creatinine ≤2.0 x ULN.
Key exclusion criteria (12 listed)
- Subjects meeting any of the following criteria will not be included in the study.
- Prior taxane and HDAC inhibitor combination therapy.
- Previous or concurrent malignancy except adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
- Clinically significant cardiac disease including congestive heart failure (New York Heart Association Class III or IV), including pre-existing ventricular arrhythmia or conduction abnormality requiring medication, or cardiomyopathy.
- Active and uncontrolled clinically significant infection.
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 |
|---|---|---|
| MGCD0103 & DocetaxelAlso: MG-0103, Taxotere®In both Parts 1 and 2, subsequent doses of MGCD0103 will be escalated in 25 mg increments until the MTD of MGCD0103 in combination with each fixed dose (60 mg/m2 or 75 mg/m2) ofIV docetaxel is determined. In both parts 1 and 2, MGCD0103 will be administered orally TIW for 3 weeks beginning on Day 1 at 1 hour prior to the start of the IV docetaxel infusion. There will be no scheduled break between cycles and no limit to the number of cycles a subject can receive provided they do not have disease progression as defined by RECIST, or a clinically significant drug-related adverse event (AE) that does not resolve or respond to treatment intervention with 3 weeks. | Drug | Part 1, Part 2 |
Primary outcome
To determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and safety profile of escalating doses of orally administered MGCD0103 in combination with two fixed doses (60 mg/m2 and 75 mg/m2) of IV docetaxel.
Time frame: 15 months
To assess the plasma pharmacokinetics (PK) of MGCD0103 (and/or its metabolites) and IV docetaxel administered in combination.
Time frame: 15 months
To evaluate potential pharmacodynamic (PD) effects of orally administered MGCD0103 in combination with IV docetaxel.
Time frame: 15 months
To determine the overall tumor response of orally administered MGCD0103 in combination with IV docetaxel according to Response Evaluation Criteria in Solid Tumors (RECIST) methodology.
Time frame: 15 months
Results and safety
The study was stopped early (reason given: Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 will be closed.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 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.
Gregory Reid, MSc, MBA study director
MethylGene Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MGCD0103 & Docetaxel in people with Breast Cancer and Lung Cancer, run by Mirati Therapeutics Inc. at 2 sites in United States.
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 10 inclusion and 12 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: stopped early, as of the sponsor's last update on 8 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 stopped early (reason given: Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 will be closed.). Results are not available in the source record.
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 maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and safety profile of escalating doses of orally administered MGCD0103 in combination with two fixed doses (60 mg/m2 and 75 mg/m2) of IV docetaxel. (time frame: 15 months). The study lists 4 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 8 Jan 2015.