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Non-Small Cell Lung CancerPhase 3NCT00499109

Phase III of RRM1 & ERCC1 Directed Customized Chemotherapy for the Treatment of Patients With NSCLC

A Phase 3 study testing Docetaxel, Vinorelbine and Carboplatin in people with Non-Small Cell Lung Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 9 sites in 3 countries.

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

This is a clinical research study to evaluate if chemotherapy in the experimental arm (E) results in a better outcome compared to patients in the standard of care arm (C). 2:1 randomization to experimental arm (E) or standard arm (C). 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?
Docetaxel, Vinorelbine and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
275 participants
Where
9 sitesin 3 countries
Study dates
May 2007to Nov 2013
Phase
Phase 3
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 Non-Small Cell Lung Cancer (NSCLC) of adenocarcinoma, squamous cell carcinoma, large cell carcinoma, or NSCLC not otherwise specified. Patients with suspected NSCLC may enroll prior to the diagnostic biopsy in order to obtain both the diagnostic and molecular analysis-required specimen during the same procedure. Must have blood work within 30 days prior to biopsy to eliminate any unnecessary biopsies on patients that do not qualify (screen failures) due to laboratory values that do not meet the inclusion/exclusion criteria. If a patient has blood work obtained at an outside facility, this can be utilized for the preliminary assessment prior to biopsy, but final inclusion/exclusion values must be obtained within 14 days of start of treatment.
  • Willing to undergo biopsy to enable customization of chemotherapy
  • Stage IV or IIIB (malignant pleural effusion) NSCLC
  • Measurable or evaluable disease by Response Evaluation Criteria In Solid Tumors (RECIST)
  • Performance status 0 or 1 by Eastern Cooperative Oncology Group (ECOG) criteria
  • Adequate bone marrow function as evidenced by the following (assessed within 14 days of starting treatment): Absolute neutrophil count >= 1,500/mm³, Platelet count >= 100,000/mm³, Hemoglobin >= 8.0 gm/dL
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  • Prothrombin time (PT) and activated prothrombin time with thromboplastin and kaolin (APTT) within normal laboratory ranges
  • Serum creatinine <= 1.5 x upper limit of normal (ULN) assessed within 14 days of starting treatment
  • Adequate liver function as evidenced by the following (assessed within 14 days of starting treatment): Total bilirubin must be within normal limits; aspartic transaminase (AST) and alanine transaminase (ALT) <= 2.5 x ULN with a normal alkaline phosphatases; alkaline phosphatases <= 4 x upper limit of normal with normal AST and ALT; patients with elevations of alk phos and AST and/or ALT will be excluded
  • Serum calcium <= 1.1 x ULN
  • Signed informed consent document
  • Women of childbearing potential must have a negative pregnancy test. Men with partners in the childbearing age group and women of childbearing potential must use effective contraception while on treatment and for 6 months thereafter.
  • Previous surgery for NSCLC (more that 30 days before study entry)
  • Previous radiotherapy (RT) is allowed if: the time between completion of RT and initiation of chemotherapy is at least 7 days; the patient has fully recovered from all toxic effects; at least one target lesion or evaluable disease is outside the radiation field
  • Previous chemotherapy allowed if the last dose was administered equal to or greater than 12 months ago. This chemotherapy must have been given in an adjuvant or neoadjuvant mode prior to or after a complete surgical resection (R0 resection) for a NSCLC.
  • Patients with stable brain metastases will be allowed to enroll. Stable brain metastases being defined as no progression of brain metastases 28 days after conclusion of definitive treatment as documented by a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain. Patients with incidentally discovered asymptomatic brain metastases may be enrolled and treated with chemotherapy without prior brain irradiation if deemed feasible by the treating physician.

Who cannot join

  • Pregnant or lactating
  • Prior systemic chemotherapy or immunotherapy for advanced NSCLC.
  • Prior malignancies, except: cured non-melanoma skin cancer curatively treated in situ carcinoma of the cervix any other curatively treated malignancy with no evidence of disease recurrence for at least 3 years
  • Presence of uncontrolled brain or leptomeningeal metastases
  • Peripheral neuropathy or hearing loss of neural origin equal to or greater than grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 except if due to trauma
  • Other serious illness or medical condition, including but not limited to: congestive heart failure, myocardial infarction within 6 months, significant neurologic or psychiatric disorders that would impact study participation as judged by the treating physician or study chair, infection requiring intravenous (IV) antibiotics, tuberculosis with ongoing therapy at study entry, superior vena cava syndrome (except if controlled with radiation), active peptic ulcer disease, uncontrolled diabetes mellitus as judged by the treating oncologist, any contraindication to high dose corticosteroid therapy (such as herpes simplex, herpes zoster, hepatitis, or other disease)
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  • Hypercalcemia requiring therapeutic intervention
  • Clinically significant ascites and/or pericardial effusion
  • Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
  • Concurrent treatment with other investigational drugs

Trial locations and contacts

9 sites in 3 countries.

9 sites in 3 countries

United States7 sites

  • Johns Hopkins Sidney Kimmell Comprehensive Cancer Center

    Baltimore, Maryland, 21231

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Center for Cancer Care & Research/Watson

    Lakeland, Florida, 33805

  • Leesburg Regional Medical Center

    Leesburg, Florida, 34748

  • Southeast Nebraska Cancer Center

    Lincoln, Nebraska, 68510-2496

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2947

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

Other trials in United States

Germany1 site

  • Klinik Loewenstein

    Löwenstein, 74245

Other trials in Germany

Puerto Rico1 site

  • Ponce School of Medicine

    Ponce, 00716

Other trials in Puerto Rico

About this study

Official title: Randomized Phase III Multicenter Trial of RRM1 & ERCC1 Directed Customized Chemotherapy Versus Standard of Care for 1st Line Treatment of Patients With Advanced Non-Small-Cell Lung Cancer

This is a clinical research study to evaluate if chemotherapy in the experimental arm (E) results in a better outcome compared to patients in the standard of care arm (C).

2:1 randomization to experimental arm (E) or standard arm (C). In arm E, treatment of dual-agent chemotherapy will be selected based on RRM1 and ERCC1 expression at the protein level. In arm C, treatment of dual-agent chemotherapy will be gemcitabine/carboplatin, i.e., standard of care.

Read the detailed description

Before each cycle, blood tests, vital signs, interim medical history, and a physical exam will be performed. Patients will be carefully checked so that immediate intervention can be initiated should an adverse event (i.e. hypersensitivity) occur.

The last treatment cycle according to the study will be cycle #6, or any earlier cycle. Certain tests will be done within 28 days after the last drug infusion. These include physical exam, vital signs, temperature, weight, adverse event evaluation, imaging studies, and blood work.

The study doctor will see the participants every 6 to 8 weeks for at least 12 months after they start treatment. After that, the participants will be followed every 3 months for an additional 24 months.

Keywords
RRM1, ERCC1, Customized Chemotherapy
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.

  • DocetaxelDrug

    Also called Taxotere

    GD Group: 40 mg/m^2 on days 1 and 8, every 21 days

    DCb Group: 75 mg/m^2 on day 1

    DV Group: 50 mg/m^2 on days 1 and 15, every 28 days

  • VinorelbineDrug

    Also called anti-cancer chemotherapy drug

    DV Group: 35 mg/m^2 on days 1 and 15

  • CarboplatinDrug

    Also called Paraplatin

    GCb Group: Area under the curve (AUC) 5 on day 1, every 21 days

    DCb Group: AUC 6 on day 1, every 21 days

    Control Arm: Patients received up to 6 cycles, and no maintenance therapy was allowed.

  • GemcitabineDrug

    Also called Gemzar

    GCb Group: 1,250 mg/m^2 on days 1 and 8

    GD Group: 1,250 mg/m^2 on days 1 and 8

    Control Arm: Patients received up to 6 cycles, and no maintenance therapy was allowed.

Study groups in NCT00499109
Study groupRoleWhat they receive
E. Dual Agent ChemotherapyExperimentalExperimental Arm E. Patients received treatment according to gene expression strata with four doublet regimens. Low ERCC1 and Low RRM1 Group - Gemcitabine (G) and Carboplatin (Cb): GCb Group. Low RRM1 and High ERCC1 Group - Gemcitabine (G) and Docetaxel (D): GD Group. High RRM1 and Low ERCC1 Group - Docetaxel (D) and Carboplatin (Cb): DCb Group. High ERCC1 and High RRM1 Group - Vinorelbine (V) and Docetaxel (D): DV Group.
Receives: Drug: Docetaxel; Drug: Vinorelbine; Drug: Carboplatin; Drug: Gemcitabine
C. Standard of Care Control ArmActive comparatorControl Arm C: Gemcitabine and Carboplatin (GCb). All patients in arm C were treated with GCb regardless of gene expression levels. Patients received up to 6 cycles, and no maintenance therapy was allowed.
Receives: Drug: Carboplatin; Drug: Gemcitabine

What is being measured

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

  1. Progression Free Survival (PFS)

    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. The data of first documented disease progression or death, as defined by Response Evaluation Criteria In Solid Tumors (RECIST), was recorded, and the time interval from randomization to that date was calculated for each patient and used to generate Kaplan-Meier survival estimates and to calculate the PFS at 6 months.

    Measured: 6 months

Secondary outcomes (2)

  1. Overall Survival (OS)

    OS at 12 months, determined from the date of randomization. The time interval from randomization to the date of death was calculated for each patient and used to generate Kaplan-Meier survival estimates and to calculate the overall survival.

    Measured: 12 months

  2. Response Rate (RR)

    Number of participants per response category. Response to treatment was determined according to Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: 6 months

Timeline

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

  1. First posted11 Jul 2007 (estimated)
  2. Study startMay 2007
  3. Primary completionApr 2013
  4. Study completionNov 2013

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
275 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00499109
Sponsor's protocol ID
MCC-15005
Other IDs
105372, IST 12223, CA129343
Status last verified
Jun 2014
First submitted
10 Jul 2007
Last updated
9 Jul 2014
Data monitoring committee
No

Publications

  • Bepler G, Williams C, Schell MJ, Chen W, Zheng Z, Simon G, Gadgeel S, Zhao X, Schreiber F, Brahmer J, Chiappori A, Tanvetyanon T, Pinder-Schenck M, Gray J, Haura E, Antonia S, Fischer JR. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013 Jul 1;31(19):2404-12. doi: 10.1200/JCO.2012.46.9783. Epub 2013 May 20.

    PubMed 23690416

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Docetaxel, Vinorelbine and Carboplatin in people with Non-Small Cell Lung Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 9 sites in 3 countries.

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 16 inclusion and 10 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 9 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Germany, Puerto Rico. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 26 Mar 2014). 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 (PFS) (time frame: 6 months). 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 NCT00499109, 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 9 Jul 2014.

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