The primary objective of this study is to establish circulating tumor cell (CTC) derived xenografts and assess the activity of novel DNA repair inhibitors as a function of DNA repair mutations detected in CTC samples (personalize DNA repair therapy).
Active, not recruiting
There are 3 cohorts for this study. Cohort A & Cohort B are for patient subjects. Patients
can participate in both cohorts simultaneously, or only one cohort per patient preference.
The investigators anticipate that most patients who participate in Cohort B will also
participate in Cohort A because Cohort A only requires a one-time blood draw at baseline.
Cohort C is for healthy volunteers. The purpose of recruiting health volunteers is purely for
testing of the CTC chip system as the investigators routinely spike (inject) tumor cell lines
in healthy human blood to ensure optimal CTC yield (quality control).
Cohort A: 20 patients with NSCLC and 20 patients with SCLC. Blood samples will be collected
from eligible patients only once at baseline. These samples will be immediately processed for
CTCs and CTC derived xenografts.
Cohort B: 15 patients with NSCLC and 15 patients with SCLC. Blood samples will be collected
from eligible patients at baseline just prior to initiation of therapy. Samples will also be
collected on day 1 of every cycle of therapy for 4 cycles (typical cycles are 21 days for
chemotherapy, 28 days for targeted therapy and 14 days for immune therapy). At the time of
initiation of the treatment break, blood samples will be collected. During the treatment
break, patients will be followed every 6-12 weeks with imaging studies, and we will collect
blood samples at each visit. At the time of disease progression in the event patient goes on
best supportive care, the last blood draw will be at the time of this decision as there will
unlikely be any further imaging studies going forward. If a patient is found to have disease
progression while on active therapy, the next blood draw will be on the first day of the next
therapy and time point of subsequent blood draws will depend on the type of therapy the
patient receives. The goal is to define whether CTC loads whether CTC loads predict symptoms,
response, and disease recurrence.
For Cohorts A & B: Investigators will make every attempt to time the blood collection to
coincide with blood collection for therapeutic purposes in order to minimize discomfort.
Blood sample collection will take place in the outpatient clinic. Patients can participate in
both cohorts simultaneously, or only one cohort per patient preference.
Cohort C: 10 subjects. Blood samples will be collected from eligible health volunteers only
once. These samples will be used to test the CTC chip system as investigators routinely spike
(inject) tumor cell lines in healthy human blood to ensure optimal CTC yield (quality
control). Two samples of peripheral blood will be collected and taken to the Principal
Investigator's lab for processing.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Cohort A (one-time blood sample) | Blood samples will be collected from eligible patients only once at baseline. These samples will be immediately processed for CTCs and CTC derived xenografts. For Cohorts A & B: Patients can participate in both cohorts simultaneously, or only one cohort per patient preference. | ||
| Cohort B (multiple blood samples) | Blood samples will be collected from eligible patients at baseline just prior to initiation of therapy. Samples will also be collected on day 1 of every cycle of therapy for 4 cycles (typical cycles are 21 days for chemotherapy, 28 days for targeted therapy and 14 days for immune therapy). At the time of initiation of the treatment break, blood samples will be collected. During the treatment break, patients will be followed every 6-12 weeks with imaging studies, and we will collect blood samples at each visit. At the time of disease progression in the event patient goes on best supportive care, the last blood draw will be at the time of this decision as there will unlikely be any further imaging studies going forward. If a patient is found to have disease progression while on active therapy, the next blood draw will be on the first day of the next therapy and time point of subsequent blood draws will depend on the type of therapy the patient receives. | ||
| Cohort C (healthy volunteers) | Blood samples will be collected from eligible health volunteers only once. These samples will be used to test the CTC chip system. Two tubes of peripheral blood will be collected and taken to the PI's lab for processing. |
Inclusion Criteria Cohort A (one-time blood sample) & Cohort B (multiple blood samples)
- Histologically or cytologically confirmed lung cancer (both non-small cell lung cancer
and small cell lung cancer are allowed)
- Stage 4 NSCLC or extensive-stage SCLC
- Newly diagnosed disease with no prior systemic therapy for advanced disease Note:
Patients that have received prior adjuvant chemotherapy or prior chemoradiotherapy for
earlier stage lung cancer are allowed if treatment was completed ≥3 months.
- Age ≥ 18 years
- Ability to understand and the willingness to sign a written informed consent document
Cohort C (healthy volunteers)
- Age > 18 years but ≤ 95 years at the time of consent
- Subjects must be English-speaking
- Must voluntarily sign the most current informed consent and HIPAA documents prior to
study participation.
- Have no prior history of malignancy in the past 2 years with the exception of basal
cell and squamous cell carcinoma of the skin. Other cancers with low potential for
metastasis, such as in situ cancers can also be enrolled as healthy volunteers.
Inclusion of Women and Minorities Both men and women of all races and ethnic groups are
eligible for this study.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | Accepts Healthy Volunteers |
| Measure: | Assess activity of novel DNA repair inhibitors as a function of DNA repair mutations detected in CTC samples |
| Time Frame: | Baseline |
| Safety Issue: | |
| Description: | All analyses will be done by disease group (i.e., NSCLC and SCLC). For the primary objective, CTC derived xenografts will be generated, and CTCs will be analyzed for DNA repair defects, and used to evaluate the activity of novel DNA repair inhibitors. We will look at CTCs by group [specific DNA defect (yes or no), treated vs untreated] using histograms and compare groups statistically using two group Satterthwaite t-tests with a 0.050 two-sided significance level. |
| Phase: | |
| Primary Purpose: | Observational |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Shadia Jalal |
November 2, 2020
