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Non-small Cell Lung CancerPhase 1/2NCT00503971

Phase I/II of Oral Vorinostat Combination With Erlotinib in NSCLC Patients With EGFR Mutations With DP After Erlotinib.

A Phase 1/2 study testing Vorinostat plus Erlotinib in people with Non-small Cell Lung Cancer, run by Spanish Lung Cancer Group at 8 sites in Spain.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is an open label, non-randomized, sequential, phase I/II trial in patients with stage IIIB or IV non-small cell lung cancer (NSCLC) with EGFR mutations after progression to Erlotinib. The study will have two parts. The first part (phase I) will be a dose finding (MTD) study to be implemented at three hospitals. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Vorinostat plus Erlotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
8 sitesSpain
Study dates
May 2008to Dec 2011
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

  • Histologically confirmed NSCLC
  • Diagnosis of advanced stage IIIB with pleural effusion or IV NSCLC
  • Previous disease progression after >= 3 months treatment with Erlotinib. Must tolerate erlotinib dose of 150 mg daily during the prior month.
  • Have demonstrated mutations at epidermal growth factor receptor (EGFR) at Exon 19 or Exon 21 (Exon 19 mutations characterized by in-frame deletions (747-750), and Exon 21 mutations resulting in L858R substitutions).
  • At least 18 years old.
  • Measurable disease as defined by the presence of at least one lesion that can be accurately measured in at least one dimension using RECIST guidelines.
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  • At least 4 weeks from any prior major surgery or radiation therapy and have adequately recovered from the toxicities and/or complications
  • ECOG performance status 0 to 2
  • Adequate bone marrow function without the current use of colony stimulating factors.
  • Adequate coagulation function.
  • Adequate liver function
  • Adequate renal function
  • Non-sterilized premenopausal female, pregnancy test must be performed and patient must agree to use barrier methods of contraception. Male patients must agree to use an adequate method of contraception.
  • Available for periodic blood sample analyses, study related assessments 15.Patient has the ability to understand and willingness to sign the informed consent form.
  • 16.Patient is able to read, understand, and complete the study questionnaires.

Who cannot join

  • Patient has been treated with any investigational agent for any indication within 4 weeks of study treatment.
  • Patient previously treated with Vorinostat or any other HDAC inhibitor for any indication in the previous 30 days.
  • Patient has history of hypersensitivity or intolerance to Erlotinib.
  • Patient has an active infection or has received intravenous antibiotic, antiviral or antifungal medications with 2 weeks
  • Patient with symptomatic central nervous system metastases with or without corticosteroids treatment.
  • Inability to take and/or tolerate oral medications.
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  • Patient has known active hepatitis B or C infection,(HIV) HIV-related malignancy.
  • Pregnant or breastfeeding.
  • Patient with a history of gastrointestinal disease, surgery
  • Patient with uncontrolled undercurrent illness or circumstances that could limit compliance with the study.
  • History of malignancy except for inactive non-melanoma skin cancer and/or in situ carcinoma of the cervix, or other solid tumor treated curatively and without evidence of recurrence for at least 5 years prior to study enrollment.
  • Patient has had prescription or non-prescription drugs or other products known to influence CYP3A4 that cannot be discontinued prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Spain8 sites

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08025

  • Instituto Universitario Dexeus

    Barcelona, 08028

  • Hospital Clinic

    Barcelona, 08036

  • Institut Catalá d'Oncologia, Centre Sanitari i Universitari de Bellvitge (CSUB)

    Barcelona, 08907

  • Institut Catalá d'Oncología, Hospital Germans Trias i Pujol

    Barcelona, 08916

  • Hospital La Paz

    Madrid, 28046

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

  • Hospital Clínico Lozano Blesa

    Zaragoza, 50009

Other trials in Spain

About this study

Official title: Sequential Phase I/II Trial of Oral Vorinostat in Combination With Erlotinib in Non-small-cell Lung Cancer Patients With Mutations at Epidermal Growth Factor Receptor With Disease Progression After Erlotinib Treatment

This is an open label, non-randomized, sequential, phase I/II trial in patients with stage IIIB or IV non-small cell lung cancer (NSCLC) with EGFR mutations after progression to Erlotinib. The study will have two parts. The first part (phase I) will be a dose finding (MTD) study to be implemented at three hospitals. The second part of the study (phase II) will asses the safety and efficacy of the combination. In this second part (phase II) patients will be treated with oral Erlotinib 150 mg P.O daily plus oral Vorinostat administered according to the results of the phase I. The study endpoints to be evaluated will include safety and response rate (RR) as primary endpoints and clinical benefit rate (CBR), time to progression, time to response, response duration and progression free survival as secondary endpoints. All the patients (phase I and II) will be treated until progression disease, unacceptable toxicity or withdrawal of the consent, and will be treated at the discretion of the principal investigator.

Read the detailed description

SAMPLE:

Patients must have histologically-confirmed diagnosis of stage IIIB or IV NSCLC, with prior treatment with Erlotinib. In the phase I study the upper expected number of patients will be eighteen. In the phase II thirty two eligible patients will be included in the study. The enrollment period will be approximately 1.5 years. All patients will be treated with Erlotinib and Vorinostat regimen. Participating hospitals will be those of the Spanish Lung Cancer Group (SLCG).

For the phase I portion, there will be 3 sites: Dr. Noemi Reguart and Dr. Rafael Rosell, Institut Catala d'Oncologia, Hospital Germans Trias i Pujol, Badalona (Barcelona, Spain), Dr. Felip Cardenal, Institut Catalan d'Oncologia. Centre Sanitari i Universitari de Bellvitge (CSUB), Hospitalet de Llobregat (Barcelona, Spain) and Dr. Lola Isla, Hospital Clinico Lozano Blesa, (Zaragoza, Spain) For the phase II portion, 10 hospitals (adding 7 to the first 3) from the Spanish Lung Cancer Group (SLCG) will be involved. Hospitals will be included during phase I study.

OBJECTIVES AND HYPOTHESES Primary Phase I

(1) To determine the MTD of oral vorinostat in combination with erlotinib and to ensure that this treatment is sufficiently safe and tolerable to permit further study.

Phase II (1) To determine the percentage of patients free of progression at 12 weeks. Hypothesis: We considered that treatment was effective if we obtained a percentage of patients free of progression at 12 weeks higher than 60%.

Secondary

(1) To determine the CBR (clinical benefit rate), response rate, time to progression, time to response, response duration, and progression free survival in patients treated with vorinostat and erlotinib in combination.

Hypothesis: CBR should be of at least 25% and it will include stable disease for at least 3 months and objective RECIST response for at least 4 weeks.

Exploratory endpoints

Molecular analysis:

Main Objective: analysis of EGFR mutations (in exons 19, 20 and 21) in serum samples at baseline (before treatment), at three months of treatment and at the end of the treatment.

Secondary Objectives: retrospective analysis of molecular markers potentially related to drug sensitivity such as E-catherin protein expression, thioredoxin serum levels; Hsp70; methylation of 14-3-3r and CHFR.

Being tested
Vorinostat plus Erlotinib
Keywords
Vorinostat, NSCLC, EGFR, Erlotinib
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • Vorinostat plus ErlotinibDrug

    Also called Zolinza® and Tarceva®

    Phase I:

    Dose level 1: 300 mg V d1-7 every 21 days plus 100 mg E daily Dose level 2: 400 mg V d1-7 every 21 days plus 100 mg E daily Dose level 2b: 300 mg V d1-7 and 15-21 every 28 days plus 100 mg E daily Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily

    Phase II:

    Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily

Study groups in NCT00503971
Study groupRoleWhat they receive
Vorinostat plus erlotinibExperimentalVorinostat plus erlotinib
Receives: Drug: Vorinostat plus Erlotinib

What is being measured

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

  1. Progression Free Survival Rate at 12 Weeks

    Progression Free Survival was defined as time from first treatment until progression or death from any cause.

    Measured: From date of first day of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 weeks

  2. Maximum Tolerated Dose (MTD) of Oral Vorinostat Phase I

    In the phase I, a classic 3 + 3 dose escalation method with 3 patients treated initially at each dose level was used. MTD was determined by testing on dose escalation cohorts: continuous full dose of erlotinib 150 mg orally (p.o.) in a daily administration(QD) and escalating doses of vorinostat p.o. at three dose levels:300 mg QD 7 days every 21 days, 400 mg QD 7 days every 21 days,and 400 mg QD, 7 days every other week. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in less than or equal to 1 in 6 patients. DLTs were defined as any Vorinostat-related Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0) Grade 3 or 4 adverse events.

    Measured: Up to 24 weeks for each dosing cohort

Secondary outcomes (2)

  1. Overall Survival

    Overall survival was defined as time from study inclusion until death

    Measured: From the date of study inclusion until end of follow up, up to 36 months.

  2. Time to Progression

    The time to progression has been defined as the time that elapses, in months, since the patient begins study treatment until the patient progresses or dies from the disease, the first thing that occurs. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: From the date of randomization until end of follow up, up to 36 months.

Timeline

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

  1. First posted19 Jul 2007 (estimated)
  2. Study startMay 2008
  3. Primary completionDec 2011
  4. Study completionDec 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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00503971
Sponsor's protocol ID
TARZO
Other IDs
2007-003646-15
Status last verified
Feb 2025
First submitted
18 Jul 2007
Last updated
7 Mar 2025
Data monitoring committee
No
Individual data sharing
No

Publications

  • Reguart N, Rosell R, Cardenal F, Cardona AF, Isla D, Palmero R, Moran T, Rolfo C, Pallares MC, Insa A, Carcereny E, Majem M, De Castro J, Queralt C, Molina MA, Taron M. Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression. Lung Cancer. 2014 May;84(2):161-7. doi: 10.1016/j.lungcan.2014.02.011. Epub 2014 Mar 2.

    PubMed 24636848

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Vorinostat plus Erlotinib in people with Non-small Cell Lung Cancer, run by Spanish Lung Cancer Group at 8 sites in Spain.

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 15 inclusion and 12 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: stopped early, as of the sponsor's last update on 7 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Spain. 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 Mar 2025). 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?

Progression Free Survival Rate at 12 Weeks (time frame: From date of first day of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 weeks). 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 NCT00503971, which also lists 1 linked publication.

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 7 Mar 2025.

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