Clinical trial NCT02145078: Gene Expression Levels in Predicting Treatment Response in Patients With Stage IV Non-small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Recurrent Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-05-22
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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:

I. 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:

I. 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:

I. 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.

Eligibility criteria: Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Baseline Marker Measurement
timeFrame: Baseline
Secondary outcomes:
measure: Change in Biomarker Expression Levels
timeFrame: Baseline to up to 8 weeks (after course 2)
measure: Overall Survival (OS)
timeFrame: From the date of protocol-specified treatment initiation to the date of death or last observation, assessed up to 12 months
measure: Progression-free Survival (PFS)
timeFrame: From the date of protocol-specified treatment initiation to the date of progression, death, or last observation, assessed up to 12 months
measure: Expression Levels of Biomarkers and Other Molecules
timeFrame: Up to 8 weeks (end of course 2)
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Gerold Bepler
role: PRINCIPAL_INVESTIGATOR
References: