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Carcinoma, Non-Small-Cell LungPhase 1/2NCT00171834

Dose Escalating Study of the Safety and Efficacy of Patupilone, q3w, in Patients With Non-small Cell Lung Cancer

A Phase 1/2 study testing Patupilone in people with Carcinoma, Non-Small-Cell Lung, run by Novartis Pharmaceuticals 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

The study objective is to evaluate the maximum tolerated dose, safety and efficacy of patupilone in patients with NSCLC who have progressed after prior chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
Patupilone
Type of treatment
Injection or infusion
How many people
89 participants
Where
4 sitesUnited States
Study dates
Aug 2003to Sep 2008
Phase
Phase 1/2
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

Who may be able to join

  • Patients with histologic or cytologic confirmation of unresectable locally advanced or metastatic NSCLC (stage IIIB with pleural effusion only / stage IV) documented before first line therapy.
  • Prior treatment with a platinum-containing regimen
  • Age ≥18 years.
  • Performance status of 0-1 on the WHO scale.
  • Life expectancy of ≥3 months.
  • NSCLC patients should have at least one measurable lesion as defined by modified RECIST criteria. If the patient has had previous radiation to the marker lesion(s), the lesion must have demonstrated progression since the radiation.
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  • NSCLC patients with controlled brain metastases are eligible to be enrolled in the brain metastases cohort at the MTD. "Controlled brain metastases" patients are defined as patients who are neurologically stable, i.e. have not experienced an increase in dose of steroidal or anticonvulsive therapy for at least 14 days prior to study entry.
  • Patients with brain metastases must be verified to have metastases secondary to NSCLC based on histology of primary and by temporal sequence of events (note: these patients are eligible even if lung disease is quiescent).
  • Patients with brain metastases must show evidence of residual disease or progression of disease since prior radiological or surgical therapy.
  • Patients with brain metastases should have at least one bidimensionally measurable intracranial lesion of minimum diameter 2 cm. Multifocal disease is permitted, but the eligibility of BM patients presenting with more than 6 intracranial lesions should be discussed with Novartis prior to enrolling the patient.
  • Patients with adequate hematologic parameters:
  • ANC ≥1.5 x 10^9/L;
  • Hb ≥9.0 g/dL,
  • Platelet count ≥100 x 10^9/L (untransfused).
  • Demonstrate the following blood chemistry laboratory values:
  • total bilirubin ≤ 1.5 x ULN;
  • AST/ALT ≤ 2.5 X ULN; (≤ 5 x ULN if hepatic metastasis is present)
  • alkaline phosphatase ≤ 2.5 x ULN; (≤ 5 x ULN if hepatic and/or bone metastasis are present)
  • serum creatinine < 2 x ULN.
  • Female patients must have a negative serum pregnancy test at screening. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal).
  • All patients of reproductive potential must agree to use an effective method of contraception during the study and three months following termination of treatment.
  • All patients must use a barrier method for contraception for sexual intercourse or avoid this for the first 5 days after patupilone infusion.
  • Written informed consent must be obtained.

Who cannot join

  • Patients who have received more than one prior chemotherapy regimen or any other systemic antineoplastic treatment including immunotherapy.
  • Patients who have received any investigational compound within the past 28 days or who are planning to receive other investigational drugs while participating in the study.
  • Patients with brain metastases who have received any prior chemotherapy regimen or any other systemic antineoplastic treatment for brain metastases.
  • Patients with brain metastases who have experienced a dose increase of 25% or more above previous dose, in concomitant steroidal or anticonvulsive therapy within 14 days prior to study entry.
  • Patients with brain metastases receiving steroidal or anticonvulsive therapy for whom a dose increase has been required within 14 days prior to start of study drug.
  • Patients with brain metastases who have leptomeningeal disease.
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  • Patients with brain metastases who have extracranial metastases in more than two organs.
  • Patients with any peripheral polyneuropathy > Grade 1.
  • Patients with unresolved diarrhea > Grade 1.
  • Patients receiving hematopoietic growth factors except erythropoietin (refer Section 3.4.4).
  • Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable cardiac or coronary artery disease.
  • Patients taking warfarin or other agents containing warfarin, with the exception of low dose warfarin (1 mg or less daily) administered prophylactically for maintenance of in-dwelling lines or ports.
  • Patients who have not recovered fully from surgery for any cause, including brain metastases patients who have had a biopsy or surgical resection of the brain tumor within 2 weeks prior to starting study drug or who are not fully recovered from any prior biopsy or surgical resection.
  • Patients who have received radiation therapy or chemotherapy within the last four weeks. Palliative radiotherapy of metastasis in extremities is allowed but such lesions cannot be used as tumor markers.
  • Patients with the presence of active or suspected acute or chronic uncontrolled infection, including abscess or fistulae.
  • Patients known to be HIV positive.
  • History of another malignancy within 3 years prior to study entry, except curatively treated non-melanotic skin cancer or cervical cancer in situ.
  • For patients enrolling in the brain metastases cohort, any of the following exclusions to MRI imaging:
  • Cardiac pacemaker Ferromagnetic metal implants other than those approved as safe for use in MRI scanners Claustrophobia Obesity (exceeding the limits of scanning equipment)
  • Pregnant or lactating females.
  • A history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits.
  • Other protocol-dependent inclusion / exclusion criteria may apply

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Ellis Fisher Cancer Center

    Columbia, Missouri, 65203

  • MD Anderson Cancer Center

    Houston, Texas, 77030-4009

  • Norton Healthcare/Hospital Inc

    Louisville, Kentucky, 40232-5070

  • Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: An Open Label, Phase I/II Dose Escalating Study Evaluating the Safety and Efficacy of EPO906, qw3, in Patients With Non-small Cell Lung Cancer.

The study objective is to evaluate the maximum tolerated dose, safety and efficacy of patupilone in patients with NSCLC who have progressed after prior chemotherapy.

Being tested
Patupilone
Keywords
EPO, EPO906, Brain metastasis, Lung cancer, Lung metastasis, NSCLC
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Brain Neoplasms, Lung Neoplasms

What participants receive

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

  • PatupiloneDrug

    Also called EPO906, Epothilone B

    Patupilone (2.5 mg/mL) was supplied as a clear, colorless concentrate for solution for infusion in glass vials containing 5 mg/2 mL in Phase I and 10 mg/4 mL in Phase II part of the study. Patupilone was administered as a single intravenous (i.v.) infusion over 5 to 10 minutes (Amendment 1) till Amendment 2 and over 10 to 20 minutes (Amendment 2) till the completion of Phase I part of the study. Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks in Phase II part of the study.

What is being measured

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

  1. Phase I: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD)

    The MTD was defined as the highest dose of patupilone administered every three weeks (q3w) where not more than one out of six patients experienced a DLT using a standard 3+3 design. Dose escalation started at 6.5 mg/m^2 until MTD in steps of 0.5 mg/m^2 until 12 mg/m^2, then in steps of 1 mg/m^2 till 13.0 mg/m^2. DLTs were assessed during cycle 1. During this time frame, no more than one DLT occurred in any of the explored dose levels up to 13 mg/m^2, thus, the MTD as defined by the protocol was not reached in this study.

    Measured: Cycle 1 (21 days)

  2. Phase II: Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)

    Overall response is the number of participants who had a complete response (CR) or a partial response (PR) based on local investigator's assessment of RECIST criteria. Per RECIST: CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a >=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease (SD), small changes that do not meet previously given criteria.

    Measured: At baseline, then every second cycle (approximately every 6 weeks), until disease progression or discontinuation. Average 18 weeks.

Secondary outcomes (6)

  1. Number of Participants With Best Overall Response-Phase I

    This was defined as the number of participants whose best overall response was CR or PR by RECIST. Per RECIST: CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a >=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease (SD), small changes that do not meet previously given criteria.

    Measured: Best achieved overall response according to RECIST from start of study until study discontinuation. Imaging was assessed every second cycle (ie. approximately every 6 weeks) until disease progression or discontinuation. Average 18 weeks

  2. Overall Survival Time-Phase I and Phase II

    Overall survival (OS) time was measured from the start of study drug to the date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last contact. Data was collected post treatment every 3 months until approximately 70% of patients have reached the survival endpoint (Phase I + Phase II).

    Measured: From start of study drug to date of death due to any cause. Follow-up after treatment discontinuation approximately every 3 months until approximately 70% of participants have reached the survival endpoint. Average 9.75 months

  3. Time to Progression (TTP)-Phase I and Phase II

    Time to progression was measured from the start of study drug to the date of first documented disease progression by RECIST, discontinuation due to disease progression, or death from underlying cancer, whichever event occurred first. If a patient had not progressed by RECIST, discontinued due to disease progression, or died from underlying cancer, TTP was censored at the time of last adequate tumor assessment. However, if a patient took any new cancer therapy prior to PD or death, then TTP was censored at the date of last adequate tumor assessment prior to the start date of new cancer therapy.

    Measured: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Average 18 weeks

  4. Duration of Stable Disease-Phase I and Phase II

    Duration of stable disease (CR, PR, or SD) by RECIST was defined as the time from start of study drug to the date of first documented disease progression or discontinuation due to disease progression, or death from underlying cancer, whichever event occured first.

    Measured: Imaging was assessed every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from treatment . Average 18 weeks

  5. Time to Overall Response -Phase I and Phase II

    Time to overall response (CR or PR) measured by RECIST was the time between study start until date of first documented response (CR or PR).

    Measured: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Average 18 weeks

  6. Duration of Overall Response -Phase I and Phase II

    Duration of overall response (CR or PR) measured by RECIST was measured from the first documented CR or PR to the date of first documented disease progression or discontinuation due to disease progression, or death from underlying cancer, whichever event occured first.

    Measured: Duration of response according to RECIST from start of study until study discontinuation. Duration of response was assessed every second cycle ( i.e. approximately every 6 weeks) until disease progression or discontinuation from study. Average 18 weeks

Timeline

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

  1. First posted15 Sep 2005 (estimated)
  2. Study startAug 2003
  3. Primary completionSep 2008
  4. Study completionSep 2008

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00171834
Sponsor's protocol ID
CEPO906A2209
Status last verified
Jan 2014
First submitted
13 Sep 2005
Last updated
5 Feb 2014

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Patupilone in people with Carcinoma, Non-Small-Cell Lung, run by Novartis Pharmaceuticals 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?

The sponsor lists 23 inclusion and 22 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 5 Feb 2014. 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 combined 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.

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 7 Jul 2011). 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?

Phase I: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD) (time frame: Cycle 1 (21 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 NCT00171834.

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 5 Feb 2014.

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