Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00047047
Tanespimycin, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing gemcitabine hydrochloride, tanespimycin and cisplatin in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial studies the side effects, best way to give, and best doses of tanespimycin with or without gemcitabine hydrochloride and cisplatin in treating patients with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- gemcitabine hydrochloride, tanespimycin and cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2002to Sep 2007
- 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
- Histologic proof of cancer that is now considered clinically unresectable
- Absolute neutrophil count (ANC) >= 1500/uL
- Platelets (PLT) >= 100,000/uL
- Total bilirubin =< 2 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) =< 2.5 x ULN
- Creatinine =< 1.5 x ULN
Show all 15Show fewer
- Alkaline phosphatase =< 2 x ULN or =< 5 x ULN if liver involvement
- Hemoglobin (Hgb) >= 9.0 g/dL
- Ability to provide informed consent
- Willingness to return to Mayo Clinic Rochester for follow up
- Life expectancy >= 12 weeks
- Willingness to provide all biologic specimens as required by the protocol; this is the mandatory translational research component
- Prior treatment with gemcitabine or cisplatin or both is allowed
- Patients who have had prior anthracycline must have a normal ejection fraction on multi gated acquisition scan (MUGA)
- Women of childbearing potential only: negative serum pregnancy test done =< 7 days prior to registration
Who cannot join
- Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- ECOG performance status (PS) 2, 3 or 4
- Uncontrolled infection
- Any of the following prior therapies:
- Chemotherapy =< 4 weeks prior to study entry
- Mitomycin C/nitrosoureas =< 6 weeks prior to study entry
Show all 36Show fewer
- Immunotherapy =< 4 weeks prior to study entry
- Biologic therapy =< 4 weeks prior to study entry
- Radiation therapy =< 4 weeks prior to study entry, or any radiation that potentially included the heart in the field (e.g., mantle)
- Radiation to > 25% of bone marrow
- Radiopharmaceuticals
- Chest radiation
- Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
- Significant cardiac disease including:
- Heart failure that meets New York Heart Association classification III or IV
- History of myocardial infarction =< one year of study entry
- Uncontrolled dysrhythmias or requiring antiarrhythmic drugs, or
- Poorly controlled angina
- Active ischemic heart disease =< 12 months prior to study entry
- Congenital long QT syndrome
- Left bundle branch block
- Central nervous system (CNS) metastases or seizure disorder
- Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, injections, intrauterine device [IUD], or abstinence, etc.) Note: Concurrent use of oral contraceptives is contraindicated
- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
- History of serious allergic reactions to eggs
- Concurrent use of drugs known to be inhibitors of the 3A4 enzyme
- >= grade 2 peripheral neuropathy, as defined by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0
- Significant underlying pulmonary disease as manifested by requirement for oxygen or pulmonary fibrosis on chest x-ray
- Use of concomitant medications that prolong or may prolong corrected QT interval (QTc)
- History of serious ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF], >= 3 beats in a row), QTc >= 450 msec for men and 470 msec for women, or left ventricular ejection fraction (LVEF) =< 40% by MUGA
- Patients with symptomatic pulmonary disease requiring medication including the following: dyspnea, dyspnea on exertion, paroxysmal nocturnal dyspnea, oxygen requirement and significant pulmonary disease, including chronic obstructive/restrictive pulmonary disease; note: patients that meet the Medicare criteria for home oxygen should be excluded from the protocol
- Patients with a prior history of cardiac or pulmonary toxicity after receiving anthracyclines such as doxorubicin, daunorubicin, mitoxantrone, bleomycin or carmustine (BCNU)
- Patients with greater or equal to grade 2 pulmonary or cardiac symptoms
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Trial Of Gemcitabine, 17-Allylaminogeldanamycin (17-AAG) And Cisplatin In Advanced Solid Tumor Patients
This phase I trial studies the side effects, best way to give, and best doses of tanespimycin with or without gemcitabine hydrochloride and cisplatin in treating patients with advanced solid tumors. Drugs used in chemotherapy, such as tanespimycin, gemcitabine hydrochloride, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Using more than one drug (combination chemotherapy) may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximally tolerated dose (MTD) of 17-AAG (tanespimycin) when given on days 1 and 8 of every 3 weeks cycle in combination with Gemzar (gemcitabine hydrochloride) and CDDP (cisplatin) (cohorts A, B, and E).
II. To determine the MTD of 17-AAG plus Gemzar when Gemzar is given on days 1 and 8 and 17-AAG is given on days 2 and 9 every 3 weeks (cohort C).
III. To determine the MTD of 17-AAG plus CDDP when given on days 1 and 8 every 3 weeks (cohort D).
IV. To define the dose-limiting toxicity of 17-AAG when used in combination with Gemzar and CDDP.
- To assess the effect of 17-AAG on surrogate markers when used in combination with Gemzar and CDDP.
VI. To report any responses observed.
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 3 treatment cohorts.
Cohort A (closed to accrual as of 3/2/04)*: Patients receive escalating doses of gemcitabine hydrochloride intravenously (IV) over 30 minutes, tanespimycin IV over 1 hour, and cisplatin IV over 2 hours on days 1 and 8. NOTE: *The maximum tolerated dose (MTD) of this 3-drug combination has been determined as of 3/2/04.
Cohort B (closed to accrual as of 3/2/05): Patients receive gemcitabine hydrochloride IV over 30 minutes, tanespimycin IV over 1 hour, and cisplatin IV over 2 hours on days 1 and 8.
Cohort C: Patients receive gemcitabine hydrochloride** IV over 30 minutes and tanespimycin IV over 1-2 hours on days 2 and 9.
Cohort D: Patients receive cisplatin** IV over 2 hours and tanespimycin IV over 1-2 hours on days 1 and 8.
Cohort E: Patients receive gemcitabine hydrochloride*, tanespimycin*, and cisplatin*** as in cohort B.
In all cohorts, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 3 months.
NOTE: **Gemcitabine hydrochloride and cisplatin dosage is constant, while 17-AAG is escalated in cohorts B, C, and D.
NOTE: ***Gemcitabine hydrochloride dosage is constant, 17-AAG is started at a higher dose level than all other cohorts, and cisplatin dosage is escalated in cohort E.
- Being tested
- gemcitabine hydrochloride, tanespimycin, cisplatin, laboratory biomarker analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Given IV
tanespimycinDrug
Also called 17-AAG
Given IV
cisplatinDrug
Also called CACP, CDDP, CPDD, DDP
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (tanespimycin, gemcitabine hydrochloride, cisplatin) | Experimental | Cohort A (closed to accrual as of 3/2/04)*: Patients receive escalating doses of gemcitabine hydrochloride intravenously (IV) over 30 minutes, tanespimycin IV over 1 hour, and cisplatin IV over 2 hours on days 1 and 8. NOTE: *The maximum tolerated dose (MTD) of this 3-drug combination has been determined as of 3/2/04.
Cohort B (closed to accrual as of 3/2/05): Patients receive gemcitabine hydrochloride IV over 30 minutes, tanespimycin IV over 1 hour, and cisplatin IV over 2 hours on days 1 and 8.
Cohort C: Patients receive gemcitabine hydrochloride** IV over 30 minutes and tanespimycin IV over 1-2 hours on days 2 and 9.
Cohort D: Patients receive cisplatin** IV over 2 hours and tanespimycin IV over 1-2 hours on days 1 and 8.
Cohort E: Patients receive gemcitabine hydrochloride*, tanespimycin*, and cisplatin*** as in cohort B.
Continued (see detailed description) Receives: Drug: gemcitabine hydrochloride; Drug: tanespimycin; Drug: cisplatin; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of tanespimycin, gemcitabine hydrochloride, and cisplatin, determined by incidence of dose-limiting toxicity (DLT) graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Measured: 21 days
Adverse events, graded according to NCI CTCAE version 3.0
The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized within each cohort. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination within each cohort. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
Measured: Up to 30 days after completion of study treatment
Secondary outcomes (2)
Number of responses, determined according to modified Response Evaluation Criteria in Solid Tumors (RECIST)
Responses will be summarized (overall and by tumor type) by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease within each cohort.
Measured: Up to 3 months after completion of study treatment
Heat shock protein (HSP)70 and HSP90 client protein expression
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. The expression levels of these proteins will be summarized at the different time points as well as percent change in their levels compared (overall and within each patient) between the different time points to assess potential drug interaction. Correlations between these laboratory correlate values and other outcome measures like toxicity and response will be carried out in an exploratory manner.
Measured: Baseline, 6, and 25 hours after start of infusion on days 1 and 8 of course 1 (cohorts B & D); prior to gemcitabine hydrochloride on day 1; pre-dose, 6, and 25 hours post-tanespimycin dose on day 2 (cohort C)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startAug 2002
- Primary completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Charles Erlichman, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00047047
- Sponsor's protocol ID
- NCI-2012-01429
- Other IDs
- MC0111, MAYO-MC0111, CDR0000257247, NCI-5291, U01CA069912
- Status last verified
- Jun 2013
- First submitted
- 3 Oct 2002
- Last updated
- 4 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial Of Gemcitabine, 17-Allylaminogeldanamycin (17-AAG) And Cisplatin In Advanced Solid Tumor Patients
- ClinicalTrials.gov ID
- NCT00047047
- Acronym / sponsor ID
- NCI-2012-01429
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Aug 2002
- Primary completion
- Sep 2007 (actual)
- First posted
- 27 Jan 2003 (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 phase I trial studies the side effects, best way to give, and best doses of tanespimycin with or without gemcitabine hydrochloride and cisplatin in treating patients with advanced solid tumors. Drugs used in chemotherapy, such as tanespimycin, gemcitabine hydrochloride, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Using more than one drug (combination chemotherapy) may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximally tolerated dose (MTD) of 17-AAG (tanespimycin) when given on days 1 and 8 of every 3 weeks cycle in combination with Gemzar (gemcitabine hydrochloride) and CDDP (cisplatin) (cohorts A, B, and E).
II. To determine the MTD of 17-AAG plus Gemzar when Gemzar is given on days 1 and 8 and 17-AAG is given on days 2 and 9 every 3 weeks (cohort C).
III. To determine the MTD of 17-AAG plus CDDP when given on days 1 and 8 every 3 weeks (cohort D).
IV. To define the dose-limiting toxicity of 17-AAG when used in combination with Gemzar and CDDP.
- To assess the effect of 17-AAG on surrogate markers when used in combination with Gemzar and CDDP.
VI. To report any responses observed.
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 3 treatment cohorts.
Cohort A (closed to accrual as of 3/2/04)*: Patients receive escalating doses of gemcitabine hydrochloride intravenously (IV) over 30 minutes, tanespimycin IV over 1 hour, and cisplatin IV over 2 hours on days 1 and 8. NOTE: *The maximum tolerated dose (MTD) of this 3-drug combination has been determined as of 3/2/04.
Cohort B (closed to accrual as of 3/2/05): Patients receive gemcitabine hydrochloride IV over 30 minutes, tanespimycin IV over 1 hour, and cisplatin IV over 2 hours on days 1 and 8.
Cohort C: Patients receive gemcitabine hydrochloride** IV over 30 minutes and tanespimycin IV over 1-2 hours on days 2 and 9.
Cohort D: Patients receive cisplatin** IV over 2 hours and tanespimycin IV over 1-2 hours on days 1 and 8.
Cohort E: Patients receive gemcitabine hydrochloride*, tanespimycin*, and cisplatin*** as in cohort B.
In all cohorts, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 3 months.
NOTE: **Gemcitabine hydrochloride and cisplatin dosage is constant, while 17-AAG is escalated in cohorts B, C, and D.
NOTE: ***Gemcitabine hydrochloride dosage is constant, 17-AAG is started at a higher dose level than all other cohorts, and cisplatin dosage is escalated in cohort E.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (tanespimycin, gemcitabine hydrochloride, cisplatin) | Experimental | Drug: gemcitabine hydrochloride, Drug: tanespimycin, Drug: cisplatin, Other: laboratory biomarker analysisCohort A (closed to accrual as of 3/2/04)*: Patients receive escalating doses of gemcitabine hydrochloride intravenously (IV) over 30 minutes, tanespimycin IV over 1 hour, and cisplatin IV over 2 hours on days 1 and 8. NOTE: *The maximum tolerated dose (MTD) of this 3-drug combination has been determined as of 3/2/04. Cohort B (closed to accrual as of 3/2/05): Patients receive gemcitabine hydrochloride IV over 30 minutes, tanespimycin IV over 1 hour, and cisplatin IV over 2 hours on days 1 and 8. Cohort C: Patients receive gemcitabine hydrochloride** IV over 30 minutes and tanespimycin IV over 1-2 hours on days 2 and 9. Cohort D: Patients receive cisplatin** IV over 2 hours and tanespimycin IV over 1-2 hours on days 1 and 8. Cohort E: Patients receive gemcitabine hydrochloride*, tanespimycin*, and cisplatin*** as in cohort B. Continued (see detailed description) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologic proof of cancer that is now considered clinically unresectable
- Absolute neutrophil count (ANC) >= 1500/uL
- Platelets (PLT) >= 100,000/uL
- Total bilirubin =< 2 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) =< 2.5 x ULN
Key exclusion criteria (36 listed)
- Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- ECOG performance status (PS) 2, 3 or 4
- Uncontrolled infection
- Any of the following prior therapies:
- Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
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 |
|---|---|---|
| gemcitabine hydrochlorideAlso: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, GemzarGiven IV | Drug | Treatment (tanespimycin, gemcitabine hydrochloride, cisplatin) |
| tanespimycinAlso: 17-AAGGiven IV | Drug | Treatment (tanespimycin, gemcitabine hydrochloride, cisplatin) |
| cisplatinAlso: CACP, CDDP, CPDD, DDPGiven IV | Drug | Treatment (tanespimycin, gemcitabine hydrochloride, cisplatin) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (tanespimycin, gemcitabine hydrochloride, cisplatin) |
Primary outcome
MTD of tanespimycin, gemcitabine hydrochloride, and cisplatin, determined by incidence of dose-limiting toxicity (DLT) graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time frame: 21 days
Adverse events, graded according to NCI CTCAE version 3.0
Time frame: Up to 30 days after completion of study treatment
The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized within each cohort. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination within each cohort. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
2 secondary outcomes
Number of responses, determined according to modified Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Up to 3 months after completion of study treatment
Heat shock protein (HSP)70 and HSP90 client protein expression
Time frame: Baseline, 6, and 25 hours after start of infusion on days 1 and 8 of course 1 (cohorts B & D); prior to gemcitabine hydrochloride on day 1; pre-dose, 6, and 25 hours post-tanespimycin dose on day 2 (cohort C)
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 4 Jun 2013.
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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.
Charles Erlichman principal investigator
Mayo Clinic
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 gemcitabine hydrochloride, tanespimycin and cisplatin in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) 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 15 inclusion and 36 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 4 Jun 2013. 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?
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?
MTD of tanespimycin, gemcitabine hydrochloride, and cisplatin, determined by incidence of dose-limiting toxicity (DLT) graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (time frame: 21 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 4 Jun 2013.