AzTrials
AzTrials

Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00121264

17-AAG and Sorafenib in Treating Patients With Unresectable or Metastatic Solid Tumors

A Phase 1 study testing sorafenib tosylate, tanespimycin and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial is studying the side effects and best dose of 17-AAG when given together with sorafenib in treating patients with unresectable or metastatic solid tumors. Drugs used in chemotherapy, such as 17-AAG, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
sorafenib tosylate, tanespimycin and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteUnited States
Study dates
Mar 2005to Jul 2010
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

  • Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  • Prior chemotherapy is allowed; patients may not have received chemotherapy for 4 weeks prior to the initiation of study treatment and must have full recovery from the acute effects of any prior chemotherapy; patients must not have had nitrosoureas or mitomycin C for 6 weeks prior to initiation of study treatment
  • Prior radiation therapy is allowed; patients must have completed radiation at least 4 weeks prior to initiation of study treatment; patients who have received prior radiation to 50% or more of their total marrow volume will be excluded
  • Prior treatment with biologic systemic therapies is permitted except for 17-AAG or Bay 43-9006 administration; prior experimental therapies (non FDA-approved agents) and immunotherapies are allowed; patients may not have received these therapies for 4 weeks prior to the initiation of study treatment and must have =< grade 2 residual toxicities from the effects of these therapies
  • ECOG performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of > 12 weeks
Show all 16Show fewer
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal; for patients with hepatic metastases, AST/ALT =< 5 x institutional upper limit of normal are permitted
  • Creatinine =< 1.5 x institutional upper limit of normal OR
  • Creatinine clearance >= 60 mL/min for patients with creatinine levels above 1.5 x institutional ULN
  • Tumor evaluation studies such as CT scans/MRI/X-rays/PSA should be performed within 28 days of starting protocol therapy
  • Patients are required to have DLCO of >= 60% on pretreatment pulmonary function tests with no symptomatic pulmonary disease
  • Women of child-bearing potential and all men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had chemotherapy, immunotherapy, biologic therapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from acute AEs due to agents administered more than 4 weeks earlier
  • Patients who have received any other investigational agents within 28 days of study entry
  • Patients may not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study except for medications that are prescribed for supportive care but potentially may have anticancer effect (i.e. megestrol acetate, dexamethasone, bisphosphonates); these medications must have been started at least 1 month prior to enrollment on study; in addition, men receiving treatment for prostate cancer will be maintained at castrate levels of testosterone by continuation of luteinizing- releasing hormone agonists
  • Patients with egg allergy are excluded as 17-AAG is formulated in egg phospholipid
  • Patients with known, symptomatic brain metastases should be excluded from this clinical trial; patients with stable or asymptomatic brain metastases are eligible but should not be taking enzyme-inducing anticonvulsants and should be maintained on stable steroid doses
  • 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
Show all 24Show fewer
  • Patients that meet the Medicare criteria for home oxygen
  • Patients with a prior history of chest radiation
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension (persistently elevated BP) or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant and nursing women are excluded from this study
  • HIV positive patients taking combination antiretroviral medications (HAART) would be excluded; HIV positive patients not being treated with anti-retroviral medications and otherwise meeting organ function criteria should be considered eligible
  • Patients receiving CYP 3A4 inter active agent are eligible but should be studied carefully and where acceptable and appropriate substitutions of non-CYP interactive drugs should be undertaken; patients on therapeutic warfarin should be switched to LMW heparin; if appropriate a hematology consult should be obtained
  • Patients with any impediment to swallowing tablets would be excluded
  • Patients taking rifampin, St. John's wort and enzyme inducing anticonvulsant agents (e.g. phenytoin, phenobarbital) are excluded
  • Patients with bleeding diathesis or patients taking oral anticoagulation with warfarin are excluded
  • The use of concomitant medications that prolong or may prolong QTc are excluded
  • Patients who have significant cardiac disease including heart failure that meet New York Heart Association (NYHA) class III and IV definitions, history of myocardial infarction within one year of study entry, uncontrolled dysrhythmias, or poorly controlled angina are excluded
  • Patients with a prior history of cardiac or pulmonary toxicity after receiving anthracyclines such as doxorubicin, daunorubicin, mitoxantrone, bleomycin or BCNU
  • Patients with a greater or equal to grade 2 pulmonary or cardiac symptoms prior to study entry
  • Patients who have a history of serious ventricular arrhythmia (VT or VF, >= 3 beats in a row), QTc> 450 msec for men and 470 msec for women, or LVEF =< 40% by MUGA are excluded
  • Patients with a history of prior radiation that potentially included the heart in the field (e.g., mantle)
  • Patients with active ischemic heart disease within 12 months
  • Patients with a history of uncontrolled dysrhythmias or requiring antiarrythmic drugs; patients with congenital long QT syndrome
  • Patients with left bundle branch block

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

Other trials in United States

About this study

Official title: A Phase I Dose-Escalation Study of Intravenous 17-Allylaminogeldanamycin (17-AAG) [NSC 330507and Oral BAY 43-9006 [NSC 724772] Administered in Patients With Pretreated Advanced Solid Tumors

This phase I trial is studying the side effects and best dose of 17-AAG when given together with sorafenib in treating patients with unresectable or metastatic solid tumors. Drugs used in chemotherapy, such as 17-AAG, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving 17-AAG together with sorafenib may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To recommend a phase II dose for 17AAG (once weekly intravenously for 3 of 4 weeks), in combination with BAY 43-9006 (twice daily orally), by determining the feasibility, safety, dose limiting toxicities and the maximally tolerated dose.

SECONDARY OBJECTIVES:

  1. To evaluate the modulation of pharmacodynamic effects and to investigate the interaction between the two mechanisms of action when used in combination by: Studying surrogate tissue and tumor cell signaling by Western blotting. Evaluating tumor blood flow utilizing dynamic contrast enhanced MRI.

II. To study any pharmacokinetic interactions between these two agents. III. To assess preliminary anti-tumor activity of this combination.

OUTLINE: This is an open-label, multicenter, dose-escalation study of 17-N-allylamino 17-demethoxygeldanamycin (17-AAG).

Patients receive oral sorafenib twice daily on days -14 to 28 in course 1 and on days 1-28 in all subsequent courses. Patients also receive 17-AAG IV over 3 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 5-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that which 2 of 6 patients experience dose-limiting toxicity.

After completion of study therapy, patients are followed for 60 days.

Being tested
sorafenib tosylate, tanespimycin, laboratory biomarker analysis, pharmacological study, magnetic resonance imaging

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sorafenib tosylateDrug

    Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar

    Given orally

  • tanespimycinDrug

    Also called 17-AAG

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • magnetic resonance imagingProcedure or surgery

    Also called MRI, NMR imaging, NMRI, nuclear magnetic resonance imaging

    Correlative studies

Study groups in NCT00121264
Study groupRoleWhat they receive
Treatment (sorafenib tosylate, tanespimycin)ExperimentalPatients receive oral sorafenib twice daily on days -14 to 28 in course 1 and on days 1-28 in all subsequent courses. Patients also receive 17-AAG IV over 3 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: sorafenib tosylate; Drug: tanespimycin; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: magnetic resonance imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by NCI CTCAE version 3.0

    Measured: 42 days

  2. DLT as assessed by NCI CTCAE version 3.0

    Measured: 42 days

Secondary outcomes (4)

  1. Pharmacokinetic parameters of sorafenib tosylate and tanespimycin

    Descriptive PK studies will be performed for the combination to determine if there is any correlation with toxicity, efficacy or interaction. Plasma concentrations will be compared with in vitro and in vivo concentrations found to be effective in pre-clinical studies.

    Measured: At baseline, at 0.5, 1, 2, 3, 4, 6, 9, and 12 hours of day 1, at 0.5, 1, and 2 hours on day 15, at 24 and 48 hours on days 16 and 17

  2. Pharmacodynamic effects of sorafenib tosylate and tanespimycin on surrogate markers and tumor tissue signaling by Western blotting

    Measured: At baseline and at day -1, 14, and 18

  3. Change in blood flow using dynamic contract enhanced MRI

    Measured: At baseline, at days -3 to 1, and at days 15-22

  4. Antitumor activity of this combination according to RECIST

    Measured: Up to 60 days after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2005 (estimated)
  2. Study startMar 2005
  3. Primary completionJul 2010
  4. Study completionJul 2010

Resources

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
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00121264
Sponsor's protocol ID
NCI-2012-03194
Other IDs
NCI-2012-03194, CDR434803, C-2890, 6972, U01CA062487, P30CA022453
Status last verified
Jan 2013
First submitted
19 Jul 2005
Last updated
17 Jun 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing sorafenib tosylate, tanespimycin and laboratory biomarker analysis 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 16 inclusion and 24 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 Jun 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?

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?

Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by NCI CTCAE version 3.0 (time frame: 42 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?

On the ClinicalTrials.gov record for NCT00121264.

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 Jun 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in