Prospective, multicenter, randomized, double-blind, placebo controlled, phase 3 study to compare efficacy and safety of masitinib to placebo in grade 2-3 non-resectable MCTs in dogs not previously treated by chemotherapy or radiotherapy.

Purpose

The primary objective of this study is to compare the safety and efficacy of masitinib to placebo in the treatment of aggressive mast cell tumors that cannot be removed with surgery.

Background

Mast cell tumors are the most common skin tumor seen in dogs. These tumors are locally aggressive, and can sometimes spread to other parts of the body. Medical therapy in the form of chemotherapy is indicated for dogs with aggressive (high grade) mast cell tumors and mast cell tumors that have spread to other parts of the body. Masitinib mesylate is an oral chemotherapy drug that inhibits the function of a group of proteins that are important for cancer cell survival and growth. Masitinib has demonstrated safety and efficacy in slowing down the progression of canine mast cell tumors that have not spread and cannot be surgically removed and has received conditional approval from the FDA for the treatment of canine mast cell tumors.

Inclusion Criteria

Eligible patients (any breed of dog) must meet all of the following criteria:

• Dog, regardless of the breed and sex older than 1 year of age and weighing more than 6.9 kg
• Dogs must have been diagnosed with Patnaik grade 2 or 3, non resectable, cutaneous mast cell tumor with or without regional lymph node involvement.
• Non resectable dog is defined as either:

- medically non resectable (margins would unlikely be free of tumor cells) or
- non resectable for the pet owner (for example, amputation would be unacceptable to the owner)

• Dog with non resectable measurable lesion at inclusion (i.e., longest diameter ≥ 10 mm for cutaneous tumor or with short axis diameters ≥ 15 mm for lymph nodes)
• Dog with lesion accessible for biopsy
• Adequate organ function:

- Absolute neutrophils count (ANC) ≥ 2000/mm3
- Platelets ≥ 100^109/L
- Hemoglobin ≥10g/dL
- Hematocrit ≥ 30%
- AST/ALT ≤ 3 x ULN
- Bilirubin ≤ 1.5 ULN
- Albumin ≥ LLN
- Creatinine ≤ ULN
- BUN ≤ ULN
- Urinary protein creatinine ratio (UPC) ≤ 1

• Owner able and willing to comply with study visits and procedures per protocol
• Owner able to understand, sign, and date consent form


Exclusion Criteria

• Dog previously treated by chemotherapy or radiotherapy
• Dog with internal metastasis
• Dog with bone marrow involvement
• Dog with major surgery within 2 weeks of treatment initiation
• Dog with evidence of gastric bleeding
• Dog with any previous history of kidney disease or any previous known episode of proteinuria including post vaccinal proteinuria
• Dog with other concomitant serious diseases (life expectancy less than 3 months)
• Lactating or pregnant bitch, dog intended for breeding
• Dog owned by staff associated with the study
• Dog with any GI disease associated with an active exudative enteropathy or past history of exudative enteropathy

Previous treatment

• Dog treated with any investigational agent within 4 weeks prior to baseline for short-acting investigational agent, and within 12 weeks prior to baseline for long-acting investigational agent
• Dog with any vaccination within 4 weeks prior to baseline
• Dog treated with corticosteroids, within 3 weeks of treatment initiation

Study Design

Screening tests that will be performed in order to confirm your dog is eligible for enrollment include the following: complete blood count, serum chemistry panel, urinalysis, chest x-rays, abdominal ultrasound, fine needle aspiration of the spleen, bone marrow aspirate, tumor biopsy, and c-kit mutation analysis. If deemed eligible, your dog will be randomized to receive either masitinib or placebo by mouth once per day. Your dog will return every 2 weeks for 1 year, then every 12 weeks thereafter if your dog has experienced a complete response, partial response or stable disease after treatment. Standard bloodwork and urinalysis will be performed at each visit. Additional tests to be performed at various points in the study include chest x-rays, abdominal ultrasound, and fine needle aspiration. Based on previous studies of masitinib in dogs with mast cell tumors, side effects that may occur include vomiting and diarrhea. Medications will be provided to treat/prevent any treatment related side effects.

Client Compensation

• The clinical trial will cover all costs associated with screening prior to study entry, all treatments associated with the study, and treatment of any side effects associated with masitinib administration.
• Additionally, if your dog’s tumor should progress during treatment then a credit of $350 will be available at the Veterinary Medical Center for continued treatment of your dog’s tumor with additional therapies.

Contact

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