Tumors
Conditions
Brief summary
A study to evaluate biomarkers of cancer (context-specific sensitizers) in the skin of participants already receiving cytotoxic therapy. Additional blood and urine samples will be collected for phosphorylated Histone 2AX (γH2AX) and renal toxicity biomarker testing, respectively.
Interventions
OTHERBiomarker sample collection before and after dosing with cytotoxic agent(s)
Participants will have blood and urine samples collected at Visit 1. After allocation, punch skin biopsies, plucked hair samples, blood, and urine will be collected at baseline, and at 24 and 48 hours post dosing with cytotoxic agent(s).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Participant has solid tumor that will be treated with one of the following treatments: * Gemcitabine monotherapy * Cisplatin monotherapy * Carboplatin monotherapy * Gemcitabine and cisplatin combination therapy * Gemcitabine and erlotinib combination therapy * Gemcitabine and carboplatin combination therapy * Cisplatin and vinorelbine combination therapy * Cisplatin and pemetrexed combination therapy * Carboplatin and vinorelbine combination therapy * Carboplatin and pemetrexed combination therapy
Exclusion criteria
* Participant has had recent cancer treatments including chemotherapy or radiation * Participant has been in an investigational study within the last 30 days * Participant has a history of drug or alcohol abuse * Participant is Human Immunodeficiency Virus (HIV) positive or has a history of Hepatitis B or C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of Biomarkers | Baseline, 24, 32, and 48 hours post dose | Phospho-CDC2 (pCDC2) response in the skin following the administration of cytotoxic agents. pCDC2 levels were measured by immunohistochemistry (IHC). |
| Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 24, 32, and 48 hours post dose | Ratio of Phospho-CDC2 (pCDC2) response at 24, 32, and 48 hours compared to baseline, 24, and 32 hours post chemotherapy. |
Participant flow
Pre-assignment details
There were 36 participants enrolled. Of these, 4 from Group I and 1 from Group II did not have evaluable biopsies and were considered not evaluable. Data only reflect the evaluable population (15 from Group I and 16 from Group II).
Participants by arm
| Arm | Count |
|---|---|
| Biomarker Evaluation Group I Participants who had blood and urine samples collected at Visit 1. After allocation, punch skin biopsies, plucked hair samples, blood, and urine were collected at baseline, and at 24 and 48 hours post dosing with cytotoxic agent(s). An additional sample collection at 32 hours may have been performed if deemed necessary after review of the data. | 15 |
| Biomarker Evaluation Group II A second group of participants who had blood and urine samples collected at Visit 1 (there was no baseline). After allocation, punch skin biopsies, plucked hair samples, blood, and urine were collected at at 24, 32 and 48 hours post dosing with cytotoxic agent(s). | 16 |
| Total | 31 |
Baseline characteristics
| Characteristic | Biomarker Evaluation Group I | Total | Biomarker Evaluation Group II |
|---|---|---|---|
| Age, Customized 29-77 years | 15 participants | 15 participants | 0 participants |
| Age, Customized 34-88 years | 0 participants | 16 participants | 16 participants |
| Sex: Female, Male Female | 5 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Male | 10 Participants | 19 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 15 | 2 / 16 |
| serious Total, serious adverse events | 0 / 15 | 0 / 16 |
Outcome results
Primary
Level of Biomarkers
Phospho-CDC2 (pCDC2) response in the skin following the administration of cytotoxic agents. pCDC2 levels were measured by immunohistochemistry (IHC).
Time frame: Baseline, 24, 32, and 48 hours post dose
Population: Actual number of participants analyzed in Part I varied from 13 to 15, depending on time point. Actual number of participants analyzed in Part II was 16 for all time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Biomarker Evaluation Group I | Level of Biomarkers | 48 hours post chemotherapy | 50.3 Percent pCDC2-positive cells | 90% Confidence Interval 1.7 |
| Biomarker Evaluation Group I | Level of Biomarkers | Baseline | 24.6 Percent pCDC2-positive cells | 90% Confidence Interval 1.7 |
| Biomarker Evaluation Group I | Level of Biomarkers | 24 hours post chemotherapy | 34.3 Percent pCDC2-positive cells | 90% Confidence Interval 1.9 |
| Biomarker Evaluation Group I | Level of Biomarkers | 32 hours post chemotherapy | NA Percent pCDC2-positive cells | — |
| Biomarker Evaluation Group II | Level of Biomarkers | 32 hours post chemotherapy | 23.7 Percent pCDC2-positive cells | 90% Confidence Interval 2 |
| Biomarker Evaluation Group II | Level of Biomarkers | 48 hours post chemotherapy | 29.9 Percent pCDC2-positive cells | 90% Confidence Interval 1.8 |
| Biomarker Evaluation Group II | Level of Biomarkers | 24 hours post chemotherapy | 23.0 Percent pCDC2-positive cells | 90% Confidence Interval 1.9 |
| Biomarker Evaluation Group II | Level of Biomarkers | Baseline | NA Percent pCDC2-positive cells | — |
Primary
Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy
Ratio of Phospho-CDC2 (pCDC2) response at 24, 32, and 48 hours compared to baseline, 24, and 32 hours post chemotherapy.
Time frame: 24, 32, and 48 hours post dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biomarker Evaluation Group I | Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 48 hours post chemotherapy/baseline | 2.05 Ratio | 90% Confidence Interval 1.78 |
| Biomarker Evaluation Group I | Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 48 hours/24 hours post chemotherapy | 1.47 Ratio | — |
| Biomarker Evaluation Group I | Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 32 hours/24 hours post chemotherapy | NA Ratio | — |
| Biomarker Evaluation Group I | Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 48 hours/32 hours post chemotherapy | NA Ratio | — |
| Biomarker Evaluation Group I | Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 24 hours post chemotherapy/baseline | 1.40 Ratio | 90% Confidence Interval 1.59 |
| Biomarker Evaluation Group II | Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 48 hours/32 hours post chemotherapy | 1.26 Ratio | 90% Confidence Interval 1.75 |
| Biomarker Evaluation Group II | Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 24 hours post chemotherapy/baseline | NA Ratio | — |
| Biomarker Evaluation Group II | Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 48 hours post chemotherapy/baseline | NA Ratio | — |
| Biomarker Evaluation Group II | Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 32 hours/24 hours post chemotherapy | 1.03 Ratio | 90% Confidence Interval 1.6 |
| Biomarker Evaluation Group II | Ratio of pCDC2 Response in Skin Following Administration of Cytotoxic Therapy | 48 hours/24 hours post chemotherapy | 1.30 Ratio | 90% Confidence Interval 1.8 |