Recurrent Non-small Cell Lung CancerNCT02145078
Gene Expression Levels in Predicting Treatment Response in Patients With Stage IV Non-small Cell Lung Cancer
A study testing docetaxel, pemetrexed disodium and gemcitabine hydrochloride in people with Recurrent Non-small Cell Lung Cancer and Stage IV Non-small Cell Lung Cancer, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.
Trial summary
This pilot clinical trial studies whether the levels of certain genes in the tissue and blood are related to how well patients with stage IV non-small cell lung cancer respond to chemotherapy. Genes may affect how sensitive or resistant tumors are to chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
- What is being tested?
- docetaxel, pemetrexed disodium and gemcitabine hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to 7 Mar 2017
- Phase
- Interventional
- 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 advanced stage NSCLC who are candidates for single or multi-agent first-line therapy.
- Second-line or higher therapy for any patients with NSCLC with performance status (PS) 0-2
- Maintenance therapy for patients after completion of four cycles of dual-agent platinum-based chemotherapy
- Stage IV, histologically or cytologically confirmed NSCLC; confirmation may be obtained with the first protocol-specified tumor biopsy
- White blood cell count > 3000/mm^3
- Platelet count > 100,000/mm^3
Show all 12Show fewer
- Hemoglobin > 9.0 g/dl
- A tumor lesion that can be safely biopsied as judged by the treating oncologist and physician performing the procedure and has not been radiated
- At least one unidimensionally measurable tumor lesion >= 1 cm in longest diameter using spiral CT (>= 2 cm in longest diameter by any other technique) that has not been radiated and is not located in a bone
- Performance status 0-2 by Eastern Cooperative Oncology Group criteria
- Life expectancy of >= 3 months
- Able to understand and sign the informed consent document
Who cannot join
- Therapy that does not include cisplatin, carboplatin, gemcitabine, and/or pemetrexed
- Concomitant medical or psychiatric illness that is likely to interfere with a reasonably safe execution of the treatment plan
- Concomitant malignancy other than NSCLC that requires active therapy; prior malignancies are allowed as long as the disease is controlled and does not require ongoing therapy of any kind; prior therapy must have concluded at least 1 year before treatment initiation on this protocol; exceptions are non-melanoma skin cancer, prostate cancer and prostatic intraepithelial neoplasia (PIN) treated with local intervention and deemed cured, cervical cancer and carcinoma in situ (CIS) treated with local intervention and deemed cured, and laryngeal cancer and CIS treated with local intervention and deemed cured
- Carcinomatous meningitis
- Uncontrolled central nervous system (CNS) disease
- The time interval between CNS radiation, whole brain radiation, spinal cord radiation, or radiosurgery, and initiation of protocol specified chemotherapy must be at least 1 week
Show all 11Show fewer
- Malignant pleural, pericardial, or peritoneal effusion if it is the only site of disease activity; i.e., if no other measurable tumor lesions exist
- Coagulopathy or anticoagulation therapy that cannot be safely corrected or interrupted for tumor biopsy
- Significant hepatic dysfunction, renal dysfunction, or metabolic derangement that precludes full-dose chemotherapy at the specified starting doses
- Concomitant treatment with chemotherapeutic agents for diseases other than malignancy
- Pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
United States1 site
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
About this study
Official title: A Pilot Trial of Platinum, Gemcitabine, or Pemetrexed Single- or Multi-Agent Therapy With Serial Tumor Specimen Collection in Patients With Advanced Non-Small-Cell Lung Cancer
This pilot clinical trial studies whether the levels of certain genes in the tissue and blood are related to how well patients with stage IV non-small cell lung cancer respond to chemotherapy. Genes may affect how sensitive or resistant tumors are to chemotherapy. Studying the levels of genes related to tumor response before and after chemotherapy may help doctors learn whether they can predict how well patients will respond to treatment.
Read the detailed description
PRIMARY OBJECTIVES:
- To describe the association between baseline gene expression levels at the protein and messenger ribonucleic acid (mRNA) level and best treatment response after two cycles of single-agent or multi-agent chemotherapy
SECONDARY OBJECTIVES:
- To describe changes in protein and mRNA levels of ribonucleotide reductase M1 (RRM1), thymidylate synthetase (TS), and excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) in serial biopsies obtained from patients being treated with gemcitabine (gemcitabine hydrochloride), pemetrexed (pemetrexed disodium), and platinum.
II. To describe the association between changes in marker levels and changes in tumor diameters.
TERTIARY OBJECTIVES:
- To explore the relationship between marker levels in circulating tumor cells and solid tumor specimens.
II. To explore the relationship between marker levels in viable peripheral blood mononuclear cells (PBMCs), circulating tumor cells, and tumor specimens.
III. Should sufficient amounts and numbers of tumor specimens remain after these analyses, they will be used to assess if other genes implicated in non-small cell lung cancer (NSCLC) outcome and response to treatment might be useful as prognostic or predictive markers for patient outcome.
OUTLINE:
Patients receive 1 of 3 chemotherapy regimens at the discretion of the primary oncologist, including docetaxel intravenously (IV) on day 1, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician.
After completion of study treatment, patients are followed up for 12 months.
- Being tested
- docetaxel, pemetrexed disodium, gemcitabine hydrochloride, laboratory biomarker analysis
- 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 RP 56976, Taxotere, TXT
Given IV
pemetrexed disodiumDrug
Also called ALIMTA, LY231514, MTA
Given IV
Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (chemotherapy regimen) | Experimental | Patients receive 1 of 4 chemotherapy regimens at the discretion of the primary oncologist following institutional guidelines, including cisplatin, carboplatin, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician. Receives: Drug: docetaxel; Drug: pemetrexed disodium; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline Marker Measurement
A univariable regression of continuous disease response on baseline marker value will be performed. A multivariable regression model adjusted for clinical covariates will be evaluated as well. Expression levels of RRM1, TS, BRCA1, and other molecules and disease response after course 2 will be log-transformed.
Measured: Baseline
Secondary outcomes (4)
Change in Biomarker Expression Levels
Evaluated using Pearson correlation. If data are not normally distributed after log transformation, a non-parametric method (e.g., Spearman correlation) will be used.
Measured: Baseline to up to 8 weeks (after course 2)
Overall Survival (OS)
Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the OS will be calculated.
Measured: From the date of protocol-specified treatment initiation to the date of death or last observation, assessed up to 12 months
Progression-free Survival (PFS)
Each biomarker evaluated using its expression level (continuous variable) and dichotomous form (based on a median cutoff). A univariable Cox regression model will be used to assess the relationship of expression levels of each biomarker to PFS. In addition, for the dichotomous variables, the sample will be divided into those above and below the median for each biomarker. PFS probabilities for each group will be estimated using the Kaplan-Meier method, with standard errors based on Greenwood's formula. Log rank tests will be used to determine the level of significance between survival curves. Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the PFS will be calculated.
Measured: From the date of protocol-specified treatment initiation to the date of progression, death, or last observation, assessed up to 12 months
Expression Levels of Biomarkers and Other Molecules
To assess the relationship between expression levels of RRM1, TS, BRCA1, and other molecules and demographic and disease variables, the Wilcoxon rank sum test or Kruskal-Wallis test for dichotomous or polychotomous categorical variables (such as sex, and histology) and the Spearman correlation coefficient for continuous ordinal variables (such as age or stage) will be used.
Measured: Up to 8 weeks (end of course 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2014 (estimated)
- Study startJun 2014
- Primary completion18 Jun 2015
- Study completion7 Mar 2017
Why it stopped: Slow accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barbara Ann Karmanos Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Gerold Bepler, Barbara Ann Karmanos Cancer Institute
- Investigators
- Gerold Bepler, Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02145078
- Sponsor's protocol ID
- 2013-177
- Other IDs
- NCI-2014-01023, 1402012854, 2013-177, P30CA022453
- Status last verified
- Sep 2020
- First submitted
- 20 May 2014
- Last updated
- 24 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of Platinum, Gemcitabine, or Pemetrexed Single- or Multi-Agent Therapy With Serial Tumor Specimen Collection in Patients With Advanced Non-Small-Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02145078
- Acronym / sponsor ID
- 2013-177
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Barbara Ann Karmanos Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2014
- Primary completion
- 18 Jun 2015 (actual)
- Study completion
- 7 Mar 2017 (actual)
- First posted
- 22 May 2014 (estimated)
- Results
- Posted 24 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot clinical trial studies whether the levels of certain genes in the tissue and blood are related to how well patients with stage IV non-small cell lung cancer respond to chemotherapy. Genes may affect how sensitive or resistant tumors are to chemotherapy. Studying the levels of genes related to tumor response before and after chemotherapy may help doctors learn whether they can predict how well patients will respond to treatment.
Detailed description
PRIMARY OBJECTIVES:
- To describe the association between baseline gene expression levels at the protein and messenger ribonucleic acid (mRNA) level and best treatment response after two cycles of single-agent or multi-agent chemotherapy
SECONDARY OBJECTIVES:
- To describe changes in protein and mRNA levels of ribonucleotide reductase M1 (RRM1), thymidylate synthetase (TS), and excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) in serial biopsies obtained from patients being treated with gemcitabine (gemcitabine hydrochloride), pemetrexed (pemetrexed disodium), and platinum.
II. To describe the association between changes in marker levels and changes in tumor diameters.
TERTIARY OBJECTIVES:
- To explore the relationship between marker levels in circulating tumor cells and solid tumor specimens.
II. To explore the relationship between marker levels in viable peripheral blood mononuclear cells (PBMCs), circulating tumor cells, and tumor specimens.
III. Should sufficient amounts and numbers of tumor specimens remain after these analyses, they will be used to assess if other genes implicated in non-small cell lung cancer (NSCLC) outcome and response to treatment might be useful as prognostic or predictive markers for patient outcome.
OUTLINE:
Patients receive 1 of 3 chemotherapy regimens at the discretion of the primary oncologist, including docetaxel intravenously (IV) on day 1, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician.
After completion of study treatment, patients are followed up for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (chemotherapy regimen) | Experimental | Drug: docetaxel, Drug: pemetrexed disodium, Drug: gemcitabine hydrochloride, Other: laboratory biomarker analysisPatients receive 1 of 4 chemotherapy regimens at the discretion of the primary oncologist following institutional guidelines, including cisplatin, carboplatin, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with advanced stage NSCLC who are candidates for single or multi-agent first-line therapy.
- Second-line or higher therapy for any patients with NSCLC with performance status (PS) 0-2
- Maintenance therapy for patients after completion of four cycles of dual-agent platinum-based chemotherapy
- Stage IV, histologically or cytologically confirmed NSCLC; confirmation may be obtained with the first protocol-specified tumor biopsy
- White blood cell count > 3000/mm^3
Key exclusion criteria (11 listed)
- Therapy that does not include cisplatin, carboplatin, gemcitabine, and/or pemetrexed
- Concomitant medical or psychiatric illness that is likely to interfere with a reasonably safe execution of the treatment plan
- Concomitant malignancy other than NSCLC that requires active therapy; prior malignancies are allowed as long as the disease is controlled and does not require ongoing therapy of any kind; prior therapy must have concluded at least 1 year before treatment initiation on this protocol; exceptions are non-melanoma skin cancer, prostate cancer and prostatic intraepithelial neoplasia (PIN) treated with local intervention and deemed cured, cervical cancer and carcinoma in situ (CIS) treated with local intervention and deemed cured, and laryngeal cancer and CIS treated with local intervention and deemed cured
- Carcinomatous meningitis
- Uncontrolled central nervous system (CNS) disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| docetaxelAlso: RP 56976, Taxotere, TXTGiven IV | Drug | Treatment (chemotherapy regimen) |
| pemetrexed disodiumAlso: ALIMTA, LY231514, MTAGiven IV | Drug | Treatment (chemotherapy regimen) |
| gemcitabine hydrochlorideAlso: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, GemzarGiven IV | Drug | Treatment (chemotherapy regimen) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (chemotherapy regimen) |
Primary outcome
Baseline Marker Measurement
Time frame: Baseline
A univariable regression of continuous disease response on baseline marker value will be performed. A multivariable regression model adjusted for clinical covariates will be evaluated as well. Expression levels of RRM1, TS, BRCA1, and other molecules and disease response after course 2 will be log-transformed.
4 secondary outcomes
Change in Biomarker Expression Levels
Time frame: Baseline to up to 8 weeks (after course 2)
Overall Survival (OS)
Time frame: From the date of protocol-specified treatment initiation to the date of death or last observation, assessed up to 12 months
Progression-free Survival (PFS)
Time frame: From the date of protocol-specified treatment initiation to the date of progression, death, or last observation, assessed up to 12 months
Expression Levels of Biomarkers and Other Molecules
Time frame: Up to 8 weeks (end of course 2)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Recurrent Non-small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingObservational study
Patient-Specific MRD Liquid Biopsy in Resected NSCLC: Plasma and Bronchial Washing ctDNA
Non-Small Cell Lung Cancer, Minimal Residual Disease
RecruitingPhase 3
Testing the Impact of an Anti-Cancer Drug, Atezolizumab, After Surgery to Prevent Early Stage Non-small Cell Lung Cancer From Returning, AASI-NSCLC Trial
Lung Non-Small Cell Carcinoma
RecruitingPhase 3
Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer
Advanced Lung Non-Squamous Non-Small Cell Carcinoma, Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
RecruitingPhase 1
A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
Metastatic Solid Tumor, Recurrent Solid Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerold Bepler principal investigator
Barbara Ann Karmanos Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing docetaxel, pemetrexed disodium and gemcitabine hydrochloride in people with Recurrent Non-small Cell Lung Cancer and Stage IV Non-small Cell Lung Cancer, run by Barbara Ann Karmanos Cancer Institute at 1 site 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 12 inclusion and 11 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 24 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2020). 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?
Baseline Marker Measurement (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Sep 2020; AzTrials last refreshed its copy on 6 Nov 2026.