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Advanced Adult Primary Liver CancerPhase 1NCT00031681

7-Hydroxystaurosporine and Irinotecan Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Triple Negative Breast Cancer (Currently Accruing Only Triple-negative Breast Cancer Patients Since 6/8/2007)

A Phase 1 study testing 7-hydroxystaurosporine, irinotecan hydrochloride and diagnostic laboratory biomarker analysis in people with Advanced Adult Primary Liver Cancer and Carcinoma of the Appendix, 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
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Trial summary

This phase I trial is studying the side effects and best dose of giving 7-hydroxystaurosporine together with irinotecan hydrochloride in treating patients with metastatic or unresectable solid tumors, including triple-negative breast cancer (currently enrolling only patients with triple-negative breast cancer since… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
7-hydroxystaurosporine, irinotecan hydrochloride and diagnostic laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
1 siteUnited States
Study dates
Dec 2001to Jan 2011
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

  • Part I (closed to accrual as of 6/8/2007)
  • Histologically confirmed solid tumor that is metastatic or unresectable for which standard curative measures do not exist or are no longer effective, including the following:
  • Gastrointestinal tract cancer
  • Lung cancer
  • Breast cancer
  • Ovarian cancer
Show all 60Show fewer
  • Endometrial cancer
  • Cervical cancer
  • Prostate cancer
  • Head and neck cancer
  • Patients with or without measurable or evaluable disease allowed
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques or ≥ 10 mm with spiral CT scan
  • Tumor markers allowed for evaluable disease
  • Positive bone scan, osteoblastic metastases, and pleural or peritoneal effusions are not considered measurable or evaluable disease
  • No known brain metastases
  • Part II
  • Histologically confirmed (either primary or the recurrent site) locally recurrent or metastatic breast cancer not amendable to surgery
  • Measurable disease
  • For skin lesions, documentation by color photography and estimation of lesion size with a ruler are required
  • Must have undergone prior therapy with an anthracycline and a taxane either in the adjuvant or metastatic setting
  • CNS metastasis allowed provided stable disease (i.e., no evidence of local progression) ≥ 3 months after local therapy
  • Hormone receptor status:
  • Estrogen receptor negative
  • Progesterone receptor negative
  • HER-2 not amplified by fluorescence in situ hybridization
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • More than 12 weeks
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL
  • Bilirubin normal
  • AST/ALT no greater than 3 times upper limit of normal (ULN)
  • No Gilbert's disease
  • No chronic unconjugated hyperbilirubinemia
  • Creatinine no greater than 1.5 times ULN
  • Creatinine clearance at least 60 mL/min
  • No symptomatic cardiac dysfunction
  • No symptomatic pulmonary dysfunction
  • Oxygen saturation at least 90% by pulse oximetry on room air at rest and after walking 6 minutes
  • No insulin-dependent diabetes mellitus
  • No other uncontrolled concurrent illness
  • No active or ongoing infection
  • No psychiatric illness or social situation that would preclude study entry
  • No prior allergic reactions attributed to compounds of similar chemical or biological composition to UCN-01 or irinotecan
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No concurrent granulocyte colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) during the first course of study
  • See Disease Characteristics (Part II)
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • Prior irinotecan allowed
  • Less than 4 prior chemotherapy regimens in the adjuvant and/or metastatic setting (Part II)
  • More than 4 weeks since prior radiotherapy and recovered
  • Concurrent warfarin allowed
  • Concurrent subcutaneous heparin allowed
  • No other concurrent investigational agents
  • No concurrent anticonvulsants (e.g., carbamazepine, phenobarbital, or phenytoin)
  • No concurrent combination antiretroviral therapy for HIV-positive patients

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Virginia

    Charlottesville, Virginia, 22908

Other trials in United States

About this study

Official title: A Phase I Study of UCN-01 in Combination With Irinotecan in Resistant Solid Tumor Malignancies (Part I) and in Triple Negative (ER-Negative, PgR-Negative, HER-2 Not-Amplified) Recurrent Breast Cancers (Part II)

This phase I trial is studying the side effects and best dose of giving 7-hydroxystaurosporine together with irinotecan hydrochloride in treating patients with metastatic or unresectable solid tumors, including triple-negative breast cancer (currently enrolling only patients with triple-negative breast cancer since 6/8/2007). Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving 7-hydroxystaurosporine together with irinotecan hydrochloride may help kill more cancer cells by making tumor cells more sensitive to the drug.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose of UCN-01 (7-hydroxystaurosporine) and irinotecan (irinotecan hydrochloride) in patients with resistant solid tumors. (Part I [closed to accrual as of 6/8/2007]) II. Determine the dose-limiting toxicity of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) III. Determine the types of toxic effects of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) IV. Determine the anti-tumor activity in terms of overall response rate (partial response [PR] and complete response [CR]), clinical benefit rate (PR, CR, and stable disease), and time to disease progression in patients with estrogen receptor-negative, progesterone receptor-negative, and HER-2 not amplified (triple negative) locally recurrent or metastatic breast cancer treated with this regimen. (Part II) V. Determine the side effect profile of this regimen in patients with triple negative recurrent breast cancer. (Part II)

SECONDARY OBJECTIVES:

  1. Determine any anti-tumor activity of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) II. Determine the pharmacokinetics of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) III. Determine the activity of the serum α-acid glycoprotein and correlate this level with free UCN-01 concentrations. (Part I [closed to accrual as of 6/8/2007]) IV. Determine the in vivo mechanisms of UCN-01 activity in these patients.

OUTLINE: This is a dose-escalation study.

PART I: Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1, 8, 15, and 22 and 7-hydroxystaurosporine IV over 3 hours on days 2 and 23. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride and 7-hydroxystaurosporine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Blood samples are collected periodically during study treatment.

PART II: (treatment of triple negative recurrent breast cancer): Patients receive irinotecan hydrochloride IV and 7-hydroxystaurosporine IV as in part I at the MTD and undergo blood sample collection.

Being tested
7-hydroxystaurosporine, irinotecan hydrochloride, diagnostic laboratory biomarker analysis
Medical subject headings
Appendiceal Neoplasms, Gastrointestinal Stromal Tumors, Carcinoma, Hepatocellular, Anus Neoplasms, Breast Neoplasms, Uterine Cervical Neoplasms, Colonic Neoplasms, Endometrial Neoplasms

What participants receive

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

  • 7-hydroxystaurosporineDrug

    Also called UCN-01

    Given IV

  • irinotecan hydrochlorideDrug

    Also called Campto, Camptosar, CPT-11, irinotecan

    Given IV

  • diagnostic laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00031681
Study groupRoleWhat they receive
Treatment (combination chemotherapy)ExperimentalPART I: Patients receive irinotecan hydrochloride IV over 90 minutes on days 1, 8, 15, and 22 and 7-hydroxystaurosporine IV over 3 hours on days 2 and 23. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride and 7-hydroxystaurosporine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Blood samples are collected periodically during study treatment. PART II: (treatment of triple negative recurrent breast cancer): Patients receive irinotecan hydrochloride IV and 7-hydroxystaurosporine IV as in part I at the MTD and undergo blood sample collection.
Receives: Drug: 7-hydroxystaurosporine; Drug: irinotecan hydrochloride; Other: diagnostic laboratory biomarker analysis

What is being measured

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

  1. MTD of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)

    Defined as the highest dose given to at least 6 patients in which =< 1 out of 6 experience dose limiting toxicity (DLT).

    Measured: Part I

  2. DLT of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)

    Measured: Part I

  3. Toxicities associated with irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)

    Graded using the Cancer Therapy Evaluation Program (CTEP) Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

    Measured: Continuously over study treatment

  4. Anti-tumor activity of 7-hydroxystaurosporine in combination with irinotecan hydrochloride in ER-negative, PgR-negative, HER-2 not-amplified (triple negative) recurrent breast cancer (Part II)

    Including overall response rate (partial response [PR] +complete response [CR]), clinical benefit rate (PR+CR+stable disease [SD]), and time to disease progression. 95% confidence interval will be calculated. Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

    Measured: Every 6 weeks

  5. Side effect profile of 7-hydroxystaurosporine in combination with irinotecan hydrochloride in triple negative recurrent breast cancer (Part II)

    95 % confidence interval will be calculated.

    Measured: Continuously over study treatment

Secondary outcomes (4)

  1. Anti-tumor activity of the combination of irinotecan hydrochloride and 7-hydroxystaurosporine in treatment of patients with resistant solid tumor malignancies

    Evaluated by the RECIST criteria.

    Measured: Every 6 weeks

  2. Pharmacokinetics of irinotecan hydrochloride and 7-hydroxystaurosporine when administered in combination

    Using the high-performance liquid chromatography (HPLC) assays.

    Measured: Weekly during the first 4 weeks of course 1

  3. Serum alpha-acid glycoprotein and correlate this level with free 7-hydroxystaurosporine concentrations

    Measured: Weekly during the first 4 weeks of course 1

  4. In vivo mechanistic basis for 7-hydroxystaurosporine activity

    Explored by subgroup analysis (responders versus non-responders) on pharmacodynamic measures.

    Measured: Weekly during the first 4 weeks of course 1

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startDec 2001
  3. Primary completionJan 2011

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
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00031681
Sponsor's protocol ID
NCI-2009-00019
Other IDs
NCI-2009-00019, NCI-5582, WUSM-SCC-0102, CDR0000069215, UVACC-SCC-0102, SCC 01-02, 5582, P30CA044579
Status last verified
Sep 2013
First submitted
8 Mar 2002
Last updated
30 Sep 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 7-hydroxystaurosporine, irinotecan hydrochloride and diagnostic laboratory biomarker analysis in people with Advanced Adult Primary Liver Cancer and Carcinoma of the Appendix, 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 60 inclusion and 0 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 30 Sep 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 irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I) (time frame: Part I). The study lists 5 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 NCT00031681.

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 30 Sep 2013.

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