Clinical Study of Microdosing Carboplatin in Lung or Bladder Cancer

Status:	Terminated
Conditions:	Lung Cancer, Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	1/11/2018
Start Date:	December 2010
End Date:	November 2016

A Phase 0 Clinical Trial of Microdosing Carboplatin and Molecular Profiling for Chemoresistance

Carboplatin kills cancer cells mainly through induction of DNA damage (drug-DNA adducts). The
goal of this clinical trial is to determine if chemoresistance to carboplatin can be
identified by measuring carboplatin-induced DNA monoadducts, the precursor of Pt-DNA
diadducts or crosslinks, from subtherapeutic drug doses given prior to the initiation of
chemotherapy. We hypothesize that low levels of carboplatin-DNA monoadducts and rapid
drug-DNA adduct repair correlate with chemoresistance. A highly sensitive technology, called
accelerator mass spectrometry (AMS), will be used to measure carboplatin-DNA monoadducts from
patient samples. AMS can measure C-14 at the attomole level in specimens of milligram size.
In this study, patients will receive one non-toxic "microdose" (defined as 1/100th the
therapeutic dose) of C-14-labeled carboplatin. Blood specimens will be drawn for
determination of carboplatin-DNA monoadduct formation and repair in peripheral blood
mononuclear cells (PBMC), and pharmacokinetics (PK) will be determined from serum
ultrafiltrate. In patients microdosed prior to providing tumor samples, a few milligrams of
leftover tumor biopsy/resection specimens will be analyzed for formation of carboplatin-DNA
monoadducts. Patients will subsequently receive carboplatin-based chemotherapy. The levels of
microdose-induced carboplatin-DNA monoadducts will be correlated with response to
chemotherapy. Some blood and biopsy samples will be assayed by RT-PCR for several putative
resistance markers at the mRNA level. Side effects will also be monitored and compared to the
AMS data. This trial will also utilize PK, DNA repair and pharmacogenomics data in order to
determine some of the underlying chemoresistance mechanisms.

Inclusion Criteria:

- Participants must have clinical diagnosis of lung or bladder cancer. The term
"clinical diagnosis" means that patients are diagnosed with NSCLC or bladder
transitional cell carcinoma (TCC) based on imaging studies, but will need further
biopsy/resection to obtain tissue in order to confirm the diagnosis. However, some
patients may not have cancer as determined by pathology examination of the tissue, or
may have a different cancer after biopsy/resection is performed. If the diagnosis of
NSCLC or bladder cancer is confirmed, platinum-based chemotherapy must be planned
either for neoadjuvant chemotherapy for Stage II or above bladder cancer, or
palliative therapy for stage III or IV lung or bladder cancer regardless of patient
participation in this study. Stage II or above TCC patients and stage IV NSCLC
patients that will receive platinum-based chemotherapy will be eligible for this
study. Patients with Stage III or IV lung or bladder cancer must have measurable
lesion(s).

- Prior radiation or surgery is allowed, but should be finished at least 2 weeks prior
to study enrollment. If a participant has prior radiation therapy, at least one
measurable lesion outside of the radiation field should be available for the
evaluation of response to chemotherapy.

- Participants must be 18 years or older. We do not see any patients with NSCLC or
bladder TCC are diagnosed under the age of 18 years.

- ECOG performance status equal or less than to 2 (Karnofsky equal to or greater than
50%).

- Life expectancy of at least 3 months.

- Participants must have normal organ and marrow function as defined below: Absolute
neutrophil count greater than/equal to 1,500/microL; Platelet count greater than/equal
to 100,000/microL; Total bilirubin less than 1.5 X ULN; AST (SGOT) less than/equal to
2.5 X ULN; Creatinine less than 1.5 X ULN

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
30 days after study participation.

- Ability to understand and willing to sign a written informed consent document.

Exclusion Criteria:

- Patients must not receive concomitant radiation with chemotherapy if they do not have
any measurable lesions outside of the radiation field.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Participants who are pregnant or nursing.

- Participants who are allergic to platinum agents.

- Participants who receive chemotherapy before that includes cisplatin, carboplatin or
oxaliplatin.

We found this trial at

sites

University of California-Davis

1 Shields Ave
Sacramento, California 95616

(530) 752-1011