Gemcitabine Hydrochloride and Tanespimycin in Treating Patients With Stage IV Pancreatic Cancer
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Purpose
This randomized phase II trial is studying three different schedules of gemcitabine hydrochloride and tanespimycin to see how well they work in treating patients with stage IV pancreatic cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and tanespimycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells
| Condition | Intervention | Phase |
|---|---|---|
|
Adenocarcinoma of the Pancreas Recurrent Pancreatic Cancer Stage IV Pancreatic Cancer |
Drug: gemcitabine hydrochloride Drug: tanespimycin |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Trial of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Combination With Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma |
- Survival rate in patients with metastatic pancreatic adenocarcinoma receiving tanespimycin in combination with gemcitabine hydrochloride [ Time Frame: 6 months ] [ Designated as safety issue: No ]A patient that is alive at 6 months is considered a treatment "success". The largest success proportion where the proposed treatment regimen would be considered ineffective in this patient population is 40%, and the smallest success proportion that would warrant subsequent studies with the proposed regimen in this patient population is 60%. Estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
- Overall survival [ Time Frame: Time from registration to death due to any cause, assessed up to 2 years ] [ Designated as safety issue: No ]Estimated using the method of Kaplan-Meier.
- Time to disease progression [ Time Frame: Time from registration to documentation of disease progression, assessed up to 2 years ] [ Designated as safety issue: No ]Estimated using the method of Kaplan-Meier. Evaluated using RECIST criteria.
- Confirmed response rate [ Time Frame: 2 consecutive evaluations at least 4 weeks within the first 6 courses of treatment ] [ Designated as safety issue: No ]Evaluated using RECIST criteria.
- Duration of response [ Time Frame: The date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented ] [ Designated as safety issue: No ]Evaluated using RECIST criteria.
- Time to treatment failure [ Time Frame: The time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 2 years ] [ Designated as safety issue: No ]Evaluated using RECIST criteria.
- Adverse events in patients with metastatic pancreatic adenocarcinoma receiving tanespimycin in combination with gemcitabine hydrochloride [ Time Frame: At each course and at the end of treatment ] [ Designated as safety issue: Yes ]Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns.
- Number of circulating tumor cells [ Time Frame: Baseline, day 1 of each course, and days 2 and 3 of course 1 ] [ Designated as safety issue: No ]Analyzed by reverse transcriptase-polymerase chain reaction, immunofluorescence, and immunohistochemistry.
- Levels of intracellular targets, such as CDK4, akt, phospho-akt, Hsp90, Hsp70, and CHK1 [ Time Frame: Baseline, day 1 of each course, and days 2 and 3 of course 1 ] [ Designated as safety issue: No ]Analyzed by reverse transcriptase-polymerase chain reaction, immunofluorescence, and immunohistochemistry.
- Correlation of single nucleotide DNA polymorphisms of tanespimycin and gemcitabine hydrochloride metabolizing and target genes with survival, progression, response, and adverse events [ Time Frame: Baseline, day 1 of each course, and days 2 and 3 of course 1 ] [ Designated as safety issue: Yes ]Analyzed by reverse transcriptase-polymerase chain reaction, immunofluorescence, and immunohistochemistry.
- Correlation of Vav1 expression in primary tumor and circulating tumor cells with clinical outcomes [ Time Frame: Baseline, day 1 of each course, and days 2 and 3 of course 1 ] [ Designated as safety issue: No ]Analyzed by reverse transcriptase-polymerase chain reaction, immunofluorescence, and immunohistochemistry.
| Estimated Enrollment: | 72 |
| Study Start Date: | March 2008 |
| Primary Completion Date: | January 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I (combination chemotherapy)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and tanespimycin IV over 1 hour on day 9 of course one.
|
Drug: gemcitabine hydrochloride
Given IV
Other Names:
Drug: tanespimycin
Given IV
Other Name: 17-AAG
|
|
Experimental: Arm II (combination chemotherapy)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and tanespimycin IV over 1 hour on days 2 and 9 of course one.
|
Drug: gemcitabine hydrochloride
Given IV
Other Names:
Drug: tanespimycin
Given IV
Other Name: 17-AAG
|
|
Experimental: Arm III (combination chemotherapy)
Patients receive gemcitabine hydrochloride IV over 30 minutes on day 8 and tanespimycin IV over 1 hour on days 1 and 9 of course one. Beginning with course two (and for all subsequent courses), all patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and tanespimycin IV over 1 hour on days 2 and 9.
|
Drug: gemcitabine hydrochloride
Given IV
Other Names:
Drug: tanespimycin
Given IV
Other Name: 17-AAG
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To assess the effect of gemcitabine hydrochloride and tanespimycin (17-AAG) on 6-month survival rate in patients with stage IV pancreatic adenocarcinoma.
SECONDARY OBJECTIVES:
I. To determine the overall survival of these patients. II. To determine the time to disease progression (TTP) in these patients. III. To determine the confirmed response rate and duration of response in these patients.
IV. To determine the time to treatment failure in these patients. V. To determine the adverse events in these patients.
TERTIARY OBJECTIVES:
I. To determine the effects of treatment on molecular targets, such as CDK4, akt, phospho-akt, Hsp90, Hsp70, and CHK1, and correlate these with clinical endpoints, including survival at 6 months, TTP, response rate, and overall survival.
II. To determine the effect of gemcitabine hydrochloride metabolizing enzyme genotype on toxicity, and clinical outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0, 1, or 2). Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and tanespimycin IV over 1 hour on day 9 of course one.
ARM II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and tanespimycin IV over 1 hour on days 2 and 9 of course one.
ARM III: Patients receive gemcitabine hydrochloride IV over 30 minutes on day 8 and tanespimycin IV over 1 hour on days 1 and 9 of course one. Beginning with course two (and for all subsequent courses), all patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and tanespimycin IV over 1 hour on days 2 and 9.
Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and periodically during treatment for pharmacogenetic studies. Tumor tissue samples that are available are also collected for laboratory studies. Samples are analyzed for number of circulating tumor cells, levels of intracellular targets (e.g., CDK4, akt, phospho-akt, Hsp90, Hsp70, and CHK1), single nucleotide DNA polymorphisms, and Vav1 expression. Samples are analyzed by reverse transcriptase-polymerase chain reaction, immunofluorescence, and immunohistochemistry.
After completion of study treatment, patients are followed periodically for up to 2 years.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Histologically or cytologically confirmed pancreatic adenocarcinoma
- Clinical stage IV disease
- No known brain metastases
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Total bilirubin normal
- AST ≤ 2.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver metastases are present)
- Creatinine normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
Ejection fraction > 40% by echocardiogram
- Patients who received prior anthracyclines must have a normal ejection fraction by echocardiogram
- QTc < 500 msec
- Pulse oximetry > 88% on room air at rest and after gentle exercise (according to Group 1Medicare Guidelines)
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tanespimycin (17-AAG) or gemcitabine hydrochloride
- No known allergy to eggs
No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study requirements
- No active ischemic heart disease within the past 12 months
- No history of uncontrolled dysrhythmias
- No congenital long QT syndrome
- No left bundle branch block
No other significant cardiac disease, including any of the following:
- New York Heart Association class III or IV heart failure
- Myocardial infarction within the past year
- Poorly controlled angina
- Uncontrolled dysrhythmias
- History of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
- No clinically significant interstitial lung disease
No symptomatic pulmonary disease requiring medication, including any of the following:
- Dyspnea
- Dyspnea on exertion
- Paroxysmal nocturnal dyspnea
- Significant pulmonary disease requiring oxygen*, including chronic obstructive/restrictive pulmonary disease
- No pulmonary or cardiac symptoms ≥ grade 2
- No history of cardiac or pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or vincristine)
- No prior chemotherapy for metastatic disease
- No prior radiotherapy to the chest
- No prior radiotherapy that potentially included the heart in the field (e.g.,mantle radiotherapy)
- More than 3 months since prior adjuvant chemotherapy or chemotherapy for locally advanced disease
- More than 3 weeks since prior radiotherapy
- No concurrent medications that prolong or may prolong QTc
- No concurrent antiarrhythmic drugs
- No concurrent prophylactic colony-stimulating factors
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Contacts and Locations More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00577889 History of Changes |
| Obsolete Identifiers: | NCT01647022 |
| Other Study ID Numbers: | NCI-2009-00156, MC0542, CDR0000445454, N01CM17104 |
| Study First Received: | December 19, 2007 |
| Last Updated: | January 30, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Adenocarcinoma Adenocarcinoma, Mucinous Pancreatic Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Cystic, Mucinous, and Serous Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases |
Gemcitabine Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Radiation-Sensitizing Agents |
ClinicalTrials.gov processed this record on June 18, 2013