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Carcinoma of Unknown PrimaryPhase 2NCT00066781

Gemcitabine and Irinotecan in Treating Patients With Cancer of Unknown Primary

A Phase 2 study testing gemcitabine hydrochloride and irinotecan hydrochloride in people with Carcinoma of Unknown Primary, run by Alliance for Clinical Trials in Oncology at 4 sites 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

RATIONALE: Drugs used in chemotherapy such as gemcitabine and irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma of Unknown Primary
What is being tested?
gemcitabine hydrochloride and irinotecan hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
4 sitesUnited States
Study dates
Feb 2004to Mar 2009
Phase
Phase 2
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

DISEASE CHARACTERISTICS:

  • Histologically confirmed carcinoma of undetermined origin, with any of the following light microscopic diagnoses:
  • Adenocarcinoma
  • Poorly differentiated non-small cell carcinoma
  • Poorly differentiated squamous cell carcinoma
  • Primary site not revealed by the following diagnostic tests:
  • Complete history and physical
  • Complete blood count and chemistries
  • Chest x-ray and/or CT scan
  • Abdominal CT scan
  • Directed evaluation of symptomatic areas
  • Mammogram in women
  • Colonoscopy in patients with liver metastases to exclude a colon primary
  • Hematoxylin and eosin (H\&E) staining OR immunostaining if H\&E results are unclear, including all of the following:
  • Keratin or epithelial membrane antigen
  • S-100 or HMB45
  • LCA (CD45)
  • Chromogranin or synaptophysin
  • Thyroid transcription factor 1
  • Measurable disease
  • Patients with any of the following conditions are not eligible:
  • Neuroendocrine tumors
  • Women with axillary node involvement only
  • Women with adenocarcinoma of the peritoneum
  • Carcinoma involving only 1 site, with resectable tumor at that site
  • Squamous cell carcinoma limited to cervical, supraclavicular, or inguinal lymph nodes
  • Men with poorly differentiated mediastinal or retroperitoneal tumor with stains suggestive of germ cell origin or serum tumor markers (AFP/HCG)
  • Men with prominent blastic bony metastases or markedly elevated prostate-specific antigen, suggesting prostate origin
  • Must be willing to provide blood and tissue samples
  • No brain or meningeal involvement

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 12 weeks

Hematopoietic

  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin must meet 1 of the following criteria:
  • Less than or equal to upper limit of normal (ULN) and no UGT1A1 genotyping is required
  • Greater than ULN but less than 2 times ULN and UGT1A1 for 6/7 genotype or 7/7 genotype patients
  • Alkaline phosphatase no greater than 3 times ULN
  • AST no greater than 3 times ULN (5 times ULN if liver metastases are present)

Renal

  • Creatinine no greater than 2.0 times ULN

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other invasive malignancy within the past 5 years
  • No other severe concurrent disease that would make the patient inappropriate for the study in the judgment of the investigator
  • No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent biologic agents
  • No concurrent filgrastim (G-CSF)

Chemotherapy

  • No prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy to more than 25% of the bone marrow
  • No concurrent radiotherapy

Surgery

  • More than 4 weeks since prior major surgery

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Cancer Resource Center - Lincoln

    Lincoln, Nebraska, 68510

  • Mercy Cancer Center at Mercy Medical Center - North Iowa

    Mason City, Iowa, 50401

  • CCOP - Missouri Valley Cancer Consortium

    Omaha, Nebraska, 68106

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase II Study Of Gemcitabine (GEMZAR) And Irinotecan (CPT-11) In Previously Untreated Patients With Measurable Disease With Unknown Primary Carcinoma

RATIONALE: Drugs used in chemotherapy such as gemcitabine and irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gemcitabine together with irinotecan works in treating patients with cancer of unknown primary origin.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the response rate in patients with carcinoma of unknown primary when treated with gemcitabine and irinotecan.
  • Determine the adverse event profile and tolerability of this regimen, based on the presence or absence of the UGT1A1*28 polymorphism, in these patients. (Cohort I closed to accrual 11/17/05)
  • Determine the adverse event profile and tolerability of this regimen. (Cohort II)

Secondary

  • Determine the time to progression and overall survival of patients treated with this regimen.
  • Correlate patterns of immunohistochemical staining with response in patients treated with this regimen.
  • Correlate variation in multiple different genes, whose protein products are involved in the uptake, metabolism, and distribution of these drugs, with clinical outcomes, in terms of response and toxicity, in these patients.
  • Determine primary origin of cancer of unknown primary samples by completing a 92-gene RT-PCR cancer classification assay.
  • Determine whether the 92-gene assay results are correlated with clinical response to gemcitabine and irinotecan.

OUTLINE:

  • Cohort I (closed to accrual 11/17/05): Patients receive gemcitabine IV over 30 minutes and irinotecan IV over 90 minutes on days 1, 8, 15, and 22. Irinotecan dose may be escalated or de-escalated after course 1 depending on toxicity. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
  • Cohort II: Patients receive gemcitabine IV over 30 minutes and irinotecan IV over 90 minutes on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years.

Keywords
adenocarcinoma of unknown primary, newly diagnosed carcinoma of unknown primary, squamous cell carcinoma of unknown primary, undifferentiated carcinoma of unknown primary
Medical subject headings
Neoplasms, Unknown Primary

What participants receive

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

Study groups in NCT00066781
Study groupRoleWhat they receive
Cohort I (closed to accrual 11/17/05)ExperimentalPatients receive gemcitabine IV over 30 minutes and irinotecan IV over 90 minutes on days 1, 8, 15, and 22. Irinotecan dose may be escalated or de-escalated after course 1 depending on toxicity. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: gemcitabine hydrochloride; Drug: irinotecan hydrochloride
Cohort IIExperimentalPatients receive gemcitabine IV over 30 minutes and irinotecan IV over 90 minutes on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: gemcitabine hydrochloride; Drug: irinotecan hydrochloride

What is being measured

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

  1. Confirmed Response Rate (Partial or Complete Response for 2 Consecutive Evaluations at Least 4 Weeks Apart) as Measured by RECIST Criteria

    The primary endpoint is confirmed response rate. If measurable disease is present, a confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. All registered patients meeting the eligibility criteria that have signed a consent form and have begun treatment will be evaluable for response.

    Measured: Up to 2 years

Secondary outcomes (2)

  1. Overall Survival

    Overall survival time is defined as the time from registration to death due> to any cause. The distribution of survival time will be estimated using> the method of Kaplan-Meier . Overall survival will be calculated for> all evaluable patients combined and by group (ie. for patients with or> without the UGT1A1*28 polymorphism).

    Measured: Up to 2 years

  2. Time to Disease Progression

    Time to disease progression is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression on day 1 post-registration. The distribution of time to progression will be estimated using the method of Kaplan-Meier. Time to disease progression will be calculated for all evaluable patients combined and by group (ie. for patients with or without the UGT1A1*28 polymorphism).

    Measured: Up to 2 years

Timeline

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

  1. First posted7 Aug 2003 (estimated)
  2. Study startFeb 2004
  3. Primary completionApr 2008
  4. Study completionMar 2009

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00066781
Sponsor's protocol ID
NCCTG-N004E
Other IDs
NCI-2011-01592, CDR0000318830
Status last verified
Feb 2017
First submitted
6 Aug 2003
Last updated
4 Apr 2017
Data monitoring committee
No

Publications

  • Holtan SG, Foster NR, Erlichman CE, et al.: Gemcitabine (G) and irinotecan (CPT-11) as first-line therapy for carcinoma (ca) of unknown primary (CUP): An NCCTG phase II trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-13525, 2008.

  • Holtan SG, Steen PD, Foster NR, Erlichman C, Medeiros F, Ames MM, Safgren SL, Graham DL, Behrens RJ, Goetz MP. Gemcitabine and irinotecan as first-line therapy for carcinoma of unknown primary: results of a multicenter phase II trial. PLoS One. 2012;7(7):e39285. doi: 10.1371/journal.pone.0039285. Epub 2012 Jul 17.

    PubMed 22815703

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing gemcitabine hydrochloride and irinotecan hydrochloride in people with Carcinoma of Unknown Primary, run by Alliance for Clinical Trials in Oncology at 4 sites 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?

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 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 4 Apr 2017). 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?

Confirmed Response Rate (Partial or Complete Response for 2 Consecutive Evaluations at Least 4 Weeks Apart) as Measured by RECIST Criteria (time frame: Up to 2 years). 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 NCT00066781, which also lists 2 linked publications.

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 Apr 2017.

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