COTC018: Evaluation of iniparib in tumor bearing dogs

The Ohio State University Clinical Trials Office at the Veterinary Medical Center is currently recruiting dogs diagnosed with malignant mammary carcinoma, melanoma, oral squamous cell carcinoma, or soft tissue sarcoma to participate in a clinical trial to explore and define the biological changes in these tumors and normal tissues following exposure to the chemotherapeutic drug iniparib. This is a Comparative Oncology Trials Consortium (COTC) clinical trial coordinated through the Comparative Oncology Program at the National Cancer Institute (NCI). COTC018: Evaluation of iniparib in tumor bearing dogs to define its pharmacokinetic profile and biological activity is designed to answer questions about iniparib and its metabolite pharmacokinetics and biological activity in tumors, normal tissues and surrogates. Mining for novel biomarkers or signatures of iniparib mechanism is the study's main objective. Exposure-pharmacodynamic relationships will also be defined. Data generated through this effort will inform the use and development of iniparib for clinical studies in human cancer patients.

Inclusion Criteria:

To qualify for enrollment in this study, dogs must have:

  • histologically or cytologically confirmed melanoma, oral squamous cell carcinoma, head and neck carcinoma or soft tissue sarcoma (amenable to serial biopsy; histology may be confirmed by pre-treatment biopsy)histologically confirmed malignant mammary carcinoma (malignancy must be confirmed to establish eligibility)Enriched enrollment of at least 6 dogs with mammary carcinoma required (3-5 for control group)
  • na├»ve or recurrent (previous surgery) disease
  • favorable performance status Grade 0 or 1 (modified ECOG criteria)
  • informed owner consent for trial (approved by IACUC)
  • dogs must undergo necropsy if death occurs on study

Enrollment Evaluation:

The following are required for enrollment and can be performed at the OSU-VMC < 3 days before drug administration:

  • thoracic radiographs
  • abdominal ultrasound (if clinically indicated)
  • measurement of tumor burden (target and non target lesion assessment)
  • digital photo of tumor and other target lesions measurements
  • pre-treatment tumor and normal tissue biopsies

The following must be performed on Day 1 prior to drug administration:

  • CBC, serum biochemistry, urinalysis, coagulation profile
  • Plasma PK at time 0 and serum collection

Study Design

Mammary tumor control cohort:

  • Tumor biopsy performed days 1, 8, and 15
  • Carboplatin chemotherapy administration, day 8
  • Blood, plasma, serum collection days 1, 8, and 15
  • Off study after day 15 evaluation

Dose escalation cohort:

  • Tumor biopsy performed days 1, 8, and 15
  • CBC/chemistry/UA/coagulation profile days 1, 8, 15, and 22
  • 12-hour plasma PK, day 1Blood, plasma, serum collection days 1, 4, 8, 11, 15, and 22
  • Iniparib administration (IV over 60 min) days 1, 4, 8 and 11Carboplatin administration (IV bolus) day 11
  • Off study after day 22 evaluation
  • If progressive disease (PD) and symptomatic deterioration is documented at any point prior to this time, dogs may be removed from study and day 22 collections performed early.

Owner Compensation:

Owner compensation will consist of the sponsor covering all study associated costs once enrolled in the study as well as provide clients with a $1,000 OSU-CVM account credit for any further veterinary care for their pet.