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Advanced Solid TumorsPhase 1NCT00682279

A Phase I Study Of Oral Topotecan And Lapatinib In Subjects With Advanced Solid Tumors

A Phase 1 study testing oral topotecan (SK&F-104864); lapatinib (GW572016) in people with Advanced Solid Tumors, run by GlaxoSmithKline at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open-label, Phase I study of oral topotecan administered in combination with lapatinib in subjects with advanced solid tumors. This Phase I study will evaluate the safety, tolerability, and pharmacokinetics of oral topotecan administered in combination with lapatinib. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
oral topotecan (SK&F-104864); lapatinib (GW572016)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
Sep 2008to Mar 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

  • Subjects must provide signed, written informed consent.
  • Subjects must be ≥18 years of age.
  • Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
  • Subjects must have histologically or cytologically confirmed diagnosis of cancer.
  • Subjects must have advanced solid malignancies without an established standard of care therapy option OR progression following the most recent therapy.
  • Subjects may have measurable lesion(s) according to RECIST criteria.
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  • Subjects with stable CNS metastases or leptomeningeal involvement are eligible only if they are not taking oral steroids or CYP450 enzyme-inducing anticonvulsants.
  • Subjects must have a LVEF ≥ 50% or ≥ lower limit of normal for the institution based on MUGA scan or ECHO. The same method of cardiac evaluation must be used consistently throughout the study.
  • Subjects in the expanded cohort phase must have archived tumor tissue samples available for biomarker analysis. It is preferable that a paraffin-embedded tissue block from archived tumor tissue from the primary tumor be submitted.
  • Subjects must provide informed consent and blood samples to the pharmacogenetics research.
  • Subjects must be able to swallow and retain oral medications.
  • Subjects must have adequate hematological, hepatic, and renal function as defined: Hematologic: absolute neutrophil count (ANC) ≥1.5 X 10^9/L, hemoglobin ≥10 g/dL, platelets ≥100 X 10^9/L; Hepatic: serum bilirubin≤ upper limit of normal (ULN), AST and ALT ≤ 5 x ULN if documented liver metastases, AST and ALT ≤ 3 X ULN without liver metastases; Renal: calculated creatinine clearance ≥50 mL/min.
  • A female is eligible to enter and participate in this study if she is of:
  • Non-childbearing potential (i.e., women with functioning ovaries who have a current documented hysterectomy, or bilateral tubal ligation, or women who are post-menopausal defined as documented absence of menses for > 12 months or women with a documented bilateral oophorectomy);
  • Childbearing potential (i.e. women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at Screening (≤7 days prior to administration of first dose of investigational product), and agree to use adequate contraception beginning at least 2 weeks prior to the first does of investigational product and for 28 days after the final dose of investigational product. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:
  • An intrauterine device with a documented failure rate of less than 1% per year.
  • Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
  • Complete abstinence from sexual intercourse for 14 days before exposure to investigation product, through the clinical trial, and for at least 28 days after the last dose of investigational product.
  • Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).
  • Oral contraceptives are not reliable due to potential drug-drug interaction.
  • Male subjects with a female partner of childbearing potential are eligible to enter and participate in the study if they practice adequate barrier methods of contraception (see above) or abstinence during the study from the first dose of investigational product until 3 months after the final dose of investigational product.

Who cannot join

  • Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the first dose of investigational product or who have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
  • Subjects who have received an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of investigational product.
  • Subjects taking prohibited medications listed in the protocol.
  • Subjects with a known immediate or delayed hypersensitivity or untoward reaction to topotecan or other related compounds, or to drugs chemically related to lapatinib. These include other anilinoquinazolines, such as gefitinib, erlotinib, or other chemically-related compounds.
  • Subjects with presence of uncontrolled infection.
  • Subjects with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
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  • Subjects with uncontrolled or symptomatic angina, arrhythmias.
  • Subjects with Class II to IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  • Women who are pregnant or lactating.
  • Subjects who have received an allogeneic bone marrow transplant.
  • Subjects with any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study.
  • Subjects with psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  • Subjects with clinical history, current alcohol or illicit drug use which, in the judgment of the investigator, would interfere with the subject's ability to comply with the dosing schedule and protocol-specified evaluations.
  • Subjects with current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19104

  • GSK Investigational Site

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase I, Open-label Study of the Safety, Tolerability, and Pharmacokinetics of Oral Topotecan in Combination With Lapatinib in Subjects With Advanced Solid Tumors

This is an open-label, Phase I study of oral topotecan administered in combination with lapatinib in subjects with advanced solid tumors. This Phase I study will evaluate the safety, tolerability, and pharmacokinetics of oral topotecan administered in combination with lapatinib. This study will be conducted in two parts. Part 1 of the study will investigate the impact of lapatinib on the bioavailability of oral topotecan (bioavailability phase) and Part 2 of the study will consist of dose finding to determine the maximum-tolerated dose (MTD) regimen of the combination (dose escalation phase). In Part 2 of the study, the dose of oral topotecan will be escalated while lapatinib will be given initially as fixed doses. The primary objective of the study is to determine the MTD regimen of oral topotecan administered for five-consecutive days every 21 days in combination with daily lapatinib in subjects with advanced solid tumors.

Being tested
oral topotecan (SK&F-104864); lapatinib (GW572016)
Keywords
lapatinib, GW572016, topotecan, oral topotecan, SK&F-104864, EGFR, ErbB1, HER-2/neu, ErbB2, BCRP

What participants receive

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

  • oral topotecan (SK&F-104864); lapatinib (GW572016)Drug

    This is a single-arm, dose escalation, Phase I study in which doses of oral topotecan will be escalated and lapatinib will be given initially as a fixed dose. This study will examine oral topotecan administered on a five-consecutive day schedule in combination with daily lapatinib. This study will be conducted in two parts. Part 1 of the study will investigate the impact of lapatinib on the bioavailability of oral topotecan (bioavailability phase) and Part 2 of the study will consist of dose finding to determine the MTD regimen of the combination (dose escalation phase).

Study groups in NCT00682279
Study groupRoleWhat they receive
This is a single-arm, dose escalationNo interventionThis is a single-arm, dose escalation, Phase I study in which doses of oral topotecan will be escalated and lapatinib will be given initially as a fixed dose. This study will examine oral topotecan administered on a five-consecutive day schedule in combination with daily lapatinib. This study will be conducted in two parts. Part 1 of the study will investigate the impact of lapatinib on the bioavailability of oral topotecan (bioavailability phase) and Part 2 of the study will consist of dose finding to determine the MTD regimen of the combination (dose escalation phase).
Receives: Drug: oral topotecan (SK&F-104864); lapatinib (GW572016)

What is being measured

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

  1. The maximum-tolerated dose (MTD) regimen of the combination will be defined as the maximum dose level at which no more than one subject out of six experiences a dose-limiting toxicity (DLT) after completing one treatment cycle.

    Measured: Study cancelled prior to FCI.

Secondary outcomes (4)

  1. Adverse events and changes from baseline in laboratory values, ECGs, Multiple gated Acquisition (MUGA) scanning/Echocardiogram (ECHO), and vital signs will be evaluated to assess safety and tolerability.

    Measured: Study cancelled prior to FCI.

  2. Topotecan pharmacokinetic parameters may include AUC(0-∞), AUC(0-τ), Cmax, tmax, t½, and tlag,

    Measured: Study cancelled prior to FCI.

  3. alone and in combination with lapatinib. Lapatinib pharmacokinetic parameters may include AUC(0-τ), Cτ, Cmax, tmax, and tlag, alone and in combination with topotecan.

    Measured: Study cancelled prior to FCI.

  4. Disease assessments will be obtained every two cycles and will be recorded as tumor response (e.g. complete response [CR], partial response [PR], stable disease [SD], or progressive disease [PD]).

    Measured: Study cancelled prior to FCI.

Timeline

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

  1. First posted22 May 2008 (estimated)
  2. Study startSep 2008
  3. Primary completionMar 2011 (estimated)
  4. Study completionMar 2011 (estimated)

Why it stopped: Cancelled before enrollment

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00682279
Sponsor's protocol ID
LPT109098
Status last verified
Apr 2015
First submitted
20 May 2008
Last updated
17 Apr 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing oral topotecan (SK&F-104864); lapatinib (GW572016) in people with Advanced Solid Tumors, run by GlaxoSmithKline at 2 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?

The sponsor lists 21 inclusion and 14 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: withdrawn, as of the sponsor's last update on 17 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 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 was withdrawn before enrolling participants, so there are no results.

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?

The maximum-tolerated dose (MTD) regimen of the combination will be defined as the maximum dose level at which no more than one subject out of six experiences a dose-limiting toxicity (DLT) after completing one treatment cycle. (time frame: Study cancelled prior to FCI.). 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 NCT00682279.

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 Apr 2015.

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