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Recurrent Non-small Cell Lung CancerPhase 2NCT01928160

Pemetrexed Disodium and Carboplatin or Cisplatin With or Without Erlotinib Hydrochloride in Treating Patient With Stage IV Non-Small Cell Lung Cancer Resistant to First-Line Therapy With Erlotinib Hydrochloride or Gefitinib

A Phase 2 study testing pemetrexed disodium, carboplatin and cisplatin in people with Recurrent Non-small Cell Lung Cancer and Stage IV Non-small Cell Lung Cancer, run by Vanderbilt-Ingram Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This randomized phase II trial studies how well pemetrexed disodium and carboplatin or cisplatin with or without erlotinib hydrochloride work in treating patients with epidermal growth factor receptor (EGFR) mutant positive stage IV non-small cell lung cancer and acquired resistance to first-line therapy with… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pemetrexed disodium, carboplatin and cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jun 2014to Mar 2015
Phase
Phase 2
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

  • Signed informed consent prior to initiation of any study-specific procedure or treatment. Informed Consent Form must be signed within 14 days of study treatment initiation.
  • Age > 18 years
  • Able and willing to comply with the protocol
  • Histologically- or cytologically-confirmed Stage IV NSCLC with an EGFR exon-19 deletion or L858R mutation
  • Must have received at least 6 months of first-line therapy with erlotinib or gefitinib
  • Clinical evidence of progression on first-line EGFR TKI therapy
Show all 19Show fewer
  • Adequate hematological function within 7 days of study treatment initiation:
  • Absolute neutrophil count (ANC) > 1.5 x 109/L AND
  • Platelet count > 100 x 109/L AND
  • Hemoglobin > 9 g/dL (may be transfused to maintain or exceed this level)
  • Adequate liver function within 7 days of study treatment initiation:
  • Total bilirubin < 1.5 x upper limit of normal (ULN) AND
  • AST and ALT < 2.5 x ULN in patients without liver metastases; < 5 x ULN in patients with liver metastases
  • Adequate renal function within 7 days of study treatment initiation:
  • Serum creatinine < 1.25 x ULN or calculated creatinine clearance > 50 mL/min (Creatinine clearance may be calculated per institutional standards.)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of study treatment initiation
  • Patients with stable, treated brain metastases are eligible for study participation and may be on a stable dose of steroids at screening. Anticonvulsants (at stable dose) are allowed. Radiotherapy and stereotactic radiosurgery to the brain must be completed at least 28 days prior to randomization
  • Female patients must not be pregnant or breast-feeding. Female patients with childbearing potential should agree to use effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of at least 6 months following the last administration of study drugs. Female patients with an intact uterus (unless amenorrhoeic for the last 12 months) must have a negative serum pregnancy test within 7 days prior to randomization into the study.
  • Fertile male patients must agree to use effective contraception during the study and for a period of at least 3 months following the last administration of study drugs

Who cannot join

  • Any other prior treatment for metastatic NSCLC other than erlotinib or gefitinib. Prior adjuvant chemotherapy or concurrent chemo-radiation therapy is allowed if completed at least 12 months prior to trial enrollment
  • Radiotherapy to the brain within 28 days prior to randomization, or radiotherapy to any other site up to 14 days prior to randomization
  • Clinically significant (i.e., active) cardiovascular disease (e.g., cerebrovascular accident or myocardial infarction within 6 months prior to randomization), unstable angina, congestive heart failure (New York Heart Association Class > II), or serious cardiac arrhythmia, that is uncontrolled by medication or may interfere with administration of study treatment
  • Treatment with any other investigational agent or participation in another clinical trial that combines erlotinib with a second therapy unless the patient was on placebo.
  • Malignancies other than NSCLC within 3 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with radiation or surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
  • Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications

About this study

Official title: A Randomized Open-Label Phase II Trial of Pemetrexed and a Platinum (Carboplatin or Cisplatin) With or Without Erlotinib in Patients With Non-Small Cell Lung Cancer Harboring Activating Epidermal Growth Factor Receptor Mutations and Acquired Resistance to First-Line EGFR TKIs, Erlotinib or Gefitinib

This randomized phase II trial studies how well pemetrexed disodium and carboplatin or cisplatin with or without erlotinib hydrochloride work in treating patients with epidermal growth factor receptor (EGFR) mutant positive stage IV non-small cell lung cancer and acquired resistance to first-line therapy with erlotinib hydrochloride or gefitinib. In patients that develop resistance to first-line therapy with EGFR tyrosine kinase inhibitors (TKIs) the drug is usually stopped and the patient is switched to chemotherapy. Drugs used in chemotherapy, such as pemetrexed disodium, carboplatin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pemetrexed disodium and carboplatin or cisplatin is more effective with or without erlotinib hydrochloride in treating patients with EGFR mutant non-small cell lung cancer and acquired resistance to EGFR TKIs.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the effects of chemotherapy plus erlotinib (erlotinib hydrochloride) vs. chemotherapy alone on progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients harboring activating endothelial growth factor receptor (EGFR) mutations who developed acquired resistance to first-line therapy with erlotinib or gefitinib.

SECONDARY OBJECTIVES:

  1. To determine the overall survival (OS) and response rate in this patient population.

II. To assess the safety of erlotinib in combination with chemotherapy in this patient population.

TERTIARY OBJECTIVES:

  1. To determine whether presence of the T790M resistance mutation can be used to predict which patients will benefit from the addition of erlotinib to chemotherapy.

II. To determine if patients with NSCLC harboring activating EGFR mutations who develop acquired resistance to EGFR tyrosine-kinase inhibitors (TKIs) develop additional mutations/genetic alterations on progression.

III. To determine whether any additional biomarkers (e.g., mesenchymal-epithelial transition [MET] amplification, EGFR mutations detected in circulating free deoxyribonucleic acid [DNA]) predict response to second-line therapy in this patient population.

IV. To determine progression-free survival (PFS) in patients on the chemotherapy alone arm who crossed over to erlotinib after progression as compared to patients on the combination chemotherapy arm (erlotinib plus chemotherapy) who switched to chemotherapy of choice (without erlotinib) after progression.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21, pemetrexed disodium intravenously (IV) and carboplatin IV or cisplatin IV on day 1. Treatment repeats every 21 days for 4 courses. Patients then receive maintenance erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21 and pemetrexed disodium IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive pemetrexed disodium and carboplatin or cisplatin as in Arm I. Treatment repeats every 21 days for 4 courses. Patients then receive maintenance pemetrexed disodium as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed until death.

Being tested
pemetrexed disodium, carboplatin, cisplatin, erlotinib hydrochloride, laboratory biomarker analysis
Keywords
Non-small cell lung cancer, EGFR mutation, erlotinib acquired resistance
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.

  • pemetrexed disodiumDrug

    Also called ALIMTA, LY231514, MTA

    Given IV

  • carboplatinDrug

    Also called Carboplat, CBDCA, JM-8, Paraplat

    Given IV

  • cisplatinDrug

    Also called CACP, CDDP, CPDD, DDP

    Given IV

  • erlotinib hydrochlorideDrug

    Also called CP-358,774, erlotinib, OSI-774

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01928160
Study groupRoleWhat they receive
Arm I (chemotherapy, erlotinib hydrochloride)ExperimentalPatients receive erlotinib hydrochloride PO QD on days 1-21, pemetrexed disodium IV and carboplatin IV or cisplatin IV on day 1. Treatment repeats every 21 days for 4 courses. Patients then receive maintenance erlotinib hydrochloride PO QD on days 1-21 and pemetrexed disodium IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: pemetrexed disodium; Drug: carboplatin; Drug: cisplatin; Drug: erlotinib hydrochloride; Other: laboratory biomarker analysis
Arm II (chemotherapy)ExperimentalPatients receive pemetrexed disodium and carboplatin or cisplatin as in Arm I. Treatment repeats every 21 days for 4 courses. Patients then receive maintenance pemetrexed disodium as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: pemetrexed disodium; Drug: carboplatin; Drug: cisplatin; Other: laboratory biomarker analysis

What is being measured

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

  1. Progression free survival using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

    The Kaplan-Meier approach will be used to estimate the time-to-PFS distribution (and median PFS times) for each treatment arm. The stratified log-rank test will be used to compare the PFS distributions between the two treatment arms. The stratified Cox-regression model will be used to estimate the hazard ratio (erlotinib plus chemotherapy vs chemotherapy alone) and corresponding 80% confidence interval (CI).

    Measured: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs earlier, assessed up to 1 year

Secondary outcomes (3)

  1. Overall survival

    The Kaplan-Meier approach will be used. The stratified log-rank test will be used to compare the Overall Survival (OS) distributions between the two treatment arms. The stratified Cox-regression model will be used to estimate the hazard ratio (erlotinib plus chemotherapy vs chemotherapy alone) and corresponding 80% confidence interval (CI).

    Measured: From the date of randomization to the date of death from any cause, assessed up to 1 year

  2. Objective response rate defined as partial response (PR) and complete response (CR) using RECIST version 1.1

    An estimate of the objective response rate and its 95% CI (Blyth-Still-Casella) will be calculated for each treatment arm. The Mantel-Haenszel chi-squared test stratified according to the factors specified by EGFR activating mutation type (exon 19 deletion vs. exon 21 single point mutation), time to progression on first-line EGFR TKI (≤ 1 year vs. > 1 year), and ECOG performance status (0 vs. 1) will be used to compare the response rates between the two treatment arms. An unadjusted Fisher's exact test result will also be provided.

    Measured: Up to 1 year

  3. Number of patients with each worst grade toxicity grades 3-5 based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

    Safety will be assessed through summaries of Adverse Events (AEs), Serious Adverse Events (SAEs), deaths, grade 3 or 4 AEs, AEs with incidence rates greater than 10% (all grades), AE of grade 3 or 4 with incidence rates greater 2%, and changes in laboratory test results. Verbatim descriptions of AEs will be mapped to Medical Dictionary for Regulatory Activities (MedDRA) thesaurus terms

    Measured: Up to 45 days post-treatment

Timeline

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

  1. First posted23 Aug 2013 (estimated)
  2. Study startJun 2014
  3. Primary completionMar 2015
  4. Study completionMar 2015

Why it stopped: study not accruing

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01928160
Sponsor's protocol ID
VICC THN 1303
Other IDs
NCI-2013-01385, VICC THN 1303, P30CA068485
Status last verified
Jun 2015
First submitted
19 Aug 2013
Last updated
13 Jul 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pemetrexed disodium, carboplatin and cisplatin in people with Recurrent Non-small Cell Lung Cancer and Stage IV Non-small Cell Lung Cancer, run by Vanderbilt-Ingram Cancer Center.

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 19 inclusion and 6 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 13 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

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?

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?

Progression free survival using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (time frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs earlier, assessed up to 1 year). 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 NCT01928160.

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 13 Jul 2015.

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