Clinical Study of Microdosing Carboplatin in Lung or Bladder Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of California, Davis
Sponsor:
Collaborator:
Lawrence Livermore National Laboratory
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT01261299
First received: December 9, 2010
Last updated: September 15, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Urinary Bladder Neoplasms
Drug: Carbon-14-labeled carboplatin
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 0 Clinical Trial of Microdosing Carboplatin and Molecular Profiling for Chemoresistance

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Correlation of carboplatin-DNA monoadducts induced by microdoses of carboplatin with cancer response to carboplatin-based chemotherapy [ Time Frame: Patients will be evaluated for response to chemotherapy after they have received 2 to 3 cycles of chemo that is about 6-9 weeks after treatment is started. ] [ Designated as safety issue: No ]
    Imaging studies (including CT, MRI, PET/CT and CXR) and cystoscopy will be performed to evaluate the response. The RECIST 1.1 will be used to determine the cancer response. Tumor response, including complete response (CR, or complete disappearance) or partial response (PR, at least a 30% decrease of target lesion) will be correlated with the patient's carboplatin-DNA monoadduct levels.


Secondary Outcome Measures:
  • Determination of the underlying chemoresistance mechanisms to carboplatin [ Time Frame: The chemoresistance mechanisms will be determined from the time of this microdosing study to the time patients receive 2 to 3 cycles of chemo that is about 6-9 weeks after treatment is started. ] [ Designated as safety issue: No ]
    The half-life of carboplatin and the repair rate of DNA monoadducts (decrease of DNA monoadducts over 24 hours) in PBMC and tumor tissue will be determined and calculated. The ERCC1 expression levels will be determined with quantitative RT-PCR using beta-actin as the internal control. These parameters will be correlated with tumor response (CR or PR) to chemotherapy.


Estimated Enrollment: 80
Study Start Date: December 2010
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carbon-14-labeled carboplatin
Patients are eligible for this study if they have non-small cell lung cancer or bladder cancer and will receive cisplatin or carboplatin-based chemotherapy for the treatment of cancer. They will receive one microdose of C-14-carboplatin approximately 4 hours before scheduled biopsy/surgery. One blood draw and a few milligrams of leftover tumor tissue will be taken for analysis of carboplatin-DNA adduct levels. The dose of carboplatin will be about 1/100th the therapeutic dose.
Drug: Carbon-14-labeled carboplatin
Patients are eligible for this study if they have non-small cell lung cancer or bladder cancer and will receive cisplatin or carboplatin-based chemotherapy for the treatment of cancer. They will receive one microdose of C-14-carboplatin approximately 4 hours before scheduled biopsy/surgery. One blood draw and a few milligrams of leftover tumor tissue will be taken for analysis of carboplatin-DNA adduct levels. The dose of carboplatin will be about 1/100th the therapeutic dose.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01261299

Contacts
Contact: Chong-xian Pan, MD, PhD 916-734-3771 chong-xian.pan@ucdmc.ucdavis.edu
Contact: Paul Henderson, PhD 925-570-1615 henderson48@gmail.com

Locations
United States, California
University of California, Davis Recruiting
Sacramento, California, United States, 95817
Principal Investigator: Chong-xian Pan, MD, PhD         
Sub-Investigator: Paul Henderson, PhD         
Sponsors and Collaborators
University of California, Davis
Lawrence Livermore National Laboratory
Investigators
Study Chair: Chong-xian Pan, MD, PhD University of California, Davis
  More Information

No publications provided

Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT01261299     History of Changes
Other Study ID Numbers: UCDCC#200
Study First Received: December 9, 2010
Last Updated: September 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Davis:
Phase 0 Clinical trial
Human microdosing trial
Drug resistance, neoplasm
Carcinoma, Non-small cell lung
Urinary Bladder Neoplasm
Individualized Medicine
Carboplatin
Carboplatin-DNA adducts

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Urinary Bladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014