Advanced Solid TumorsPhase 1NCT01235897
MK-2206, Paclitaxel and Trastuzumab in Treating Patients With HER2-overexpressing Solid Tumor Malignancies
A Phase 1 study testing MK-2206, Paclitaxel and Trastuzumab in people with Advanced Solid Tumors and Tumors, run by University of California, San Francisco at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and safest highest dose of an investigational drug called MK-2206 when given in combination with paclitaxel and trastuzumab in patients with Human Epidermal growth factor Receptor 2 (HER2)-overexpressing solid tumor malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Tumors, Cancer
- What is being tested?
- MK-2206, Paclitaxel and Trastuzumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Nov 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically or cytologically-confirmed metastatic or locally advanced, unresectable HER2+ cancer. HER2+ will be defined as 3+ expression by immunohistochemistry (IHC) OR >2-fold gene amplification by Fluorescence In Situ Hybridization (FISH).
- Male or female and ≥18 years of age on the day of signing informed consent.
- Performance status of 0-2 on the ECOG Performance Scale and life expectancy > 3 months.
- Have evaluable disease. Measureable disease is not required
- Adequate organ function as indicated by the following laboratory values:
- Absolute neutrophil count (ANC) = ≥1,500 /μL
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- Platelets = ≥100,000 /μL
- Hemoglobin = ≥9 g/dL
- Serum creatinine = ≤1.5 x upper limit of normal (ULN) OR calculated creatinine clearance = ≥60 mL/min for patients with creatinine levels >1.5 x institutional ULN
- Serum total bilirubin = ≤1.5 x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 x ULN
- AST (SGOT) and ALT (SGPT) = ≤2.5 x ULN
- Prothrombin time (PT)/INR = ≤1.2 x ULN
- Partial thromboplastin time (PTT) = ≤1.2 x ULN
- Fasting serum glucose = ≤126 mg/dl
- Hemoglobin A1c (HgbA1c) = ≤7%
- Potassium = in normal range
- Female patient of childbearing potential must test negative for pregnancy and agree to the use of effective methods of contraception while on study.
- Voluntarily agree to participate by giving written informed consent.
- Able to swallow capsules and has no surgical or anatomical condition that will prevent the patient from swallowing and absorbing oral medications on an ongoing basis.
- Prior taxane, trastuzumab, lapatinib, and other HER2 directed therapy in the adjuvant or metastatic setting is allowed.
- Any number of prior lines of chemotherapy in the metastatic setting is allowed.
- Concomitant use of bisphosphonates is allowed.
- Patients with stable and clinically insignificant central nervous system (CNS) disease are allowed. Patients must be off steroids with no new CNS symptoms or findings on radiographic imaging for 1 month.
Who cannot join
- Patient who has had chemotherapy, radiotherapy, or hormonal therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. Patient must not have received trastuzumab or lapatinib within 2 weeks of study Day 1. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1.
- Less than 4 weeks post major surgical procedure (defined as one that required general anesthesia)(all surgical wounds must be fully healed).
- Currently participating or has participated in a study with an investigational compound or device within 30 days of Study Day 1.
- Known active CNS metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids that are used to minimize surrounding brain edema. Patients with clinically insignificant brain metastases that do not require treatment are eligible.
- Has a primary central nervous system tumor.
- Known hypersensitivity to the components of study drug or its analogs.
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- History or current evidence of clinically significant heart disease including:
- Left ventricular ejection fraction (LVEF) <50% on screening echocardiogram or multigated acquisition (MUGA) scan.
- Clinically significant congestive heart failure, unstable angina pectoris,
- Clinically significant cardiac arrhythmia,
- Myocardial infarction during the last 6 months, and/or a current electrocardiogram (ECG) tracing that is abnormal in the opinion of the treating Investigator,
- QTc (QT corrected) prolongation >450 msec (Bazett's Formula), congenitally long QT syndrome, and/or current anti-arrhythmic therapy, has received any marketed or experimental compound in the last 4 weeks prior to entering the study with possible or known effects of QT prolongation, or cumulative high-dose anthracycline therapy.
- Evidence of clinically significant bradycardia (heart rate <50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2), or patients taking beta blockers, non-dihydropyridine calcium channel blockers, or digoxin.
- Uncontrolled hypertension (≥140/90 mmHg). Patients who are controlled on antihypertensive medication will be allowed to enter the study.
- Significant risk for hypokalemia (e.g., patients on high dose diuretics, or with recurrent uncontrolled diarrhea)
- History or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Current regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
- Known to be Human Immunodeficiency Virus (HIV)-positive.
- Known history of Hepatitis B or C or active Hepatitis A.
- Symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible.
- Treatment with oral corticosteroids (note: inhaled corticosteroids are permitted). IV decadron pre-medication is allowed.
- Baseline neuropathy of ≥ grade 2.
- Known allergic reactions to paclitaxel or IV contrast dye despite standard prophylaxis.
- Patients who require medications that are potent CYP3A4 inhibitors or inducers. Patients who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug (whichever is longer) prior to the first dose of MK-2206.
- Patients requiring warfarin therapy. Low molecular weight heparin is permitted.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94115
About this study
Official title: A Phase Ib Dose-escalation Trial of the AKT Inhibitor MK2206 in Combination With Weekly Paclitaxel With or Without Trastuzumab
The purpose of this study is to test the safety and safest highest dose of an investigational drug called MK-2206 when given in combination with paclitaxel and trastuzumab in patients with Human Epidermal growth factor Receptor 2 (HER2)-overexpressing solid tumor malignancies.
Read the detailed description
The purpose of this study is to determine the safety and maximum tolerated dose (MTD) of MK-2206 in combination with paclitaxel and trastuzumab when given to patients with HER2-overexpressing solid tumor malignancies. MK-2206 is an oral drug (taken by mouth) that turns off a protein called AKT inside cancer cells. This could be helpful in treating treatment-resistant cancers, because AKT allows cells to survive despite active anticancer treatment. In the case of HER2-positive cancers, laboratory studies suggest that the drug combination of MK-2206 and paclitaxel and trastuzumab may be effective.
- Conditions
- Advanced Solid Tumors, Tumors, Cancer
- Being tested
- MK-2206, Paclitaxel, Trastuzumab
- Keywords
- Neoplasms, Paclitaxel, Trastuzumab
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-2206Drug
Different dose levels of MK-2206 will studied, and co-administered with paclitaxel and trastuzumab. MK-2206 will be given orally with a starting dose of 135 mg weekly
PaclitaxelDrug
80 mg/m2 weekly - paclitaxel
TrastuzumabDrug
Also called Herceptin
2 mg/kg weekly after a 1-time loading dose of 4 mg/kg - trastuzumab
| Study group | Role | What they receive |
|---|---|---|
| Maximum tolerated dose | Experimental | Not described Receives: Drug: MK-2206; Drug: Paclitaxel; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose of MK-2206 Administered Weekly in Combination With Weekly Paclitaxel 80 mg/m^2 and Trastuzumab 2 mg/m^2
The MTD was defined as the dose level resulting in 3 or fewer DLTs in 11 patients, per the modified toxicity probability interval (TPI) method (Ji Y, Li Y, Nebiyou Bekele B: Dose-finding in phase I clinical trials based on toxicity probability intervals. Clin Trials 4:235-244, 2007), and confirmed in 4 additional patients. Based on interim toxicity data from other studies, the dose was not escalated beyond 135 mg weekly.
Measured: 30 days from initiation of dose
Secondary outcomes (1)
Best Disease Response by Response Evaluation Criteria in Solid Tumor (RECIST), Version 1.1
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
Non-PR/Non-PD: clinical response of chest wall disease not evaluable by RECIST
Measured: 60 days after dose inititation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2010 (estimated)
- Study startMar 2011
- Primary completionMar 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Jo Chien, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01235897
- Sponsor's protocol ID
- 10998
- Status last verified
- Mar 2014
- First submitted
- 4 Nov 2010
- Last updated
- 17 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Dose-escalation Trial of the AKT Inhibitor MK2206 in Combination With Weekly Paclitaxel With or Without Trastuzumab
- ClinicalTrials.gov ID
- NCT01235897
- Acronym / sponsor ID
- 10998
- Conditions
- Advanced Solid Tumors, Tumors, Cancer
- Keywords
- Neoplasms, Paclitaxel, Trastuzumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2011
- Primary completion
- Mar 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 8 Nov 2010 (estimated)
- Results
- Posted 19 Nov 2013
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 safety and safest highest dose of an investigational drug called MK-2206 when given in combination with paclitaxel and trastuzumab in patients with Human Epidermal growth factor Receptor 2 (HER2)-overexpressing solid tumor malignancies.
Detailed description
The purpose of this study is to determine the safety and maximum tolerated dose (MTD) of MK-2206 in combination with paclitaxel and trastuzumab when given to patients with HER2-overexpressing solid tumor malignancies. MK-2206 is an oral drug (taken by mouth) that turns off a protein called AKT inside cancer cells. This could be helpful in treating treatment-resistant cancers, because AKT allows cells to survive despite active anticancer treatment. In the case of HER2-positive cancers, laboratory studies suggest that the drug combination of MK-2206 and paclitaxel and trastuzumab may be effective.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Maximum tolerated dose | Experimental | Drug: MK-2206, Drug: Paclitaxel, Drug: Trastuzumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Histologically or cytologically-confirmed metastatic or locally advanced, unresectable HER2+ cancer. HER2+ will be defined as 3+ expression by immunohistochemistry (IHC) OR >2-fold gene amplification by Fluorescence In Situ Hybridization (FISH).
- Male or female and ≥18 years of age on the day of signing informed consent.
- Performance status of 0-2 on the ECOG Performance Scale and life expectancy > 3 months.
- Have evaluable disease. Measureable disease is not required
- Adequate organ function as indicated by the following laboratory values:
Key exclusion criteria (27 listed)
- Patient who has had chemotherapy, radiotherapy, or hormonal therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. Patient must not have received trastuzumab or lapatinib within 2 weeks of study Day 1. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1.
- Less than 4 weeks post major surgical procedure (defined as one that required general anesthesia)(all surgical wounds must be fully healed).
- Currently participating or has participated in a study with an investigational compound or device within 30 days of Study Day 1.
- Known active CNS metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids that are used to minimize surrounding brain edema. Patients with clinically insignificant brain metastases that do not require treatment are eligible.
- Has a primary central nervous system tumor.
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 |
|---|---|---|
| MK-2206Different dose levels of MK-2206 will studied, and co-administered with paclitaxel and trastuzumab. MK-2206 will be given orally with a starting dose of 135 mg weekly | Drug | Maximum tolerated dose |
| Paclitaxel80 mg/m2 weekly - paclitaxel | Drug | Maximum tolerated dose |
| TrastuzumabAlso: Herceptin2 mg/kg weekly after a 1-time loading dose of 4 mg/kg - trastuzumab | Drug | Maximum tolerated dose |
Primary outcome
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose of MK-2206 Administered Weekly in Combination With Weekly Paclitaxel 80 mg/m^2 and Trastuzumab 2 mg/m^2
Time frame: 30 days from initiation of dose
The MTD was defined as the dose level resulting in 3 or fewer DLTs in 11 patients, per the modified toxicity probability interval (TPI) method (Ji Y, Li Y, Nebiyou Bekele B: Dose-finding in phase I clinical trials based on toxicity probability intervals. Clin Trials 4:235-244, 2007), and confirmed in 4 additional patients. Based on interim toxicity data from other studies, the dose was not escalated beyond 135 mg weekly.
1 secondary outcome
Best Disease Response by Response Evaluation Criteria in Solid Tumor (RECIST), Version 1.1
Time frame: 60 days after dose inititation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jo Chien, MD principal investigator
University of California, San Francisco
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 MK-2206, Paclitaxel and Trastuzumab in people with Advanced Solid Tumors and Tumors, run by University of California, San Francisco at 1 site 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 23 inclusion and 27 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 17 Apr 2014. 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 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?
Yes. Results are posted in the registry (first posted 19 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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) and Recommended Phase 2 Dose of MK-2206 Administered Weekly in Combination With Weekly Paclitaxel 80 mg/m^2 and Trastuzumab 2 mg/m^2 (time frame: 30 days from initiation of dose). 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 17 Apr 2014.