CytRx Corporation, a biopharmaceutical research and development company specialising in oncology, announced positive interim results from its ongoing phase 2 clinical trial evaluating the safety and efficacy of aldoxorubicin for the treatment of Kaposi's sarcoma (KS) in HIV-infected patients.
The clinical results reported are from 9 patients, 6 of which carried the worst KS prognosis. Also, 4 of the 9 patients had received from 1 to 8 prior liposomal doxorubicin (Doxil) cycles. Efficacy results revealed that all 9 patients (100 per cent) exhibited a decrease in skin lesions and in the number of cancer cells expressing the KS virus DNA. Of the 6 patients with lung tumours, 4 patients (66 per cent) demonstrated either a partial or complete response, with no patients (0 per cent) demonstrating progression. Data thus far show that aldoxorubicin can be detected in all tumour biopsies 24 hours following drug administration. Preliminary safety results showed only 2 patients (22 per cent) experienced a grade 4 adverse event (transient neutropenia and anaemia). Other adverse events were mild and most were unrelated to aldoxorubicin.
"The current standard-of-care for severe dermatological and systemic KS is Doxil, however, many patients experience significant toxicity, or exhibit minimal to no clinical response to this agent," said Steven Kriegsman, chairman and chief executive officer. of CytRx. "Aldoxorubicin has demonstrated effectiveness against a range of tumours in the phase 2 clinical trial, thus we are optimistic in regard to its potential as a treatment for KS. This data provides important insight into both the safety and efficacy of aldoxorubicin in this indication, and the lack of toxicity of our drug in these patients is very impressive. We look forward to further data using aldoxorubicin in KS as this study continues."
Assuming a positive outcome of the ongoing phase 2 clinical trial, CytRx plans to discuss with the FDA a potential pathway for the registration of aldoxorubicin for use in KS. The Company intends to submit the phase 2 KS data for presentation at the 2015 ASCO annual meeting.
This open-label phase 2 clinical trial is expected to enroll up to 30 patients, randomly assigned to three equally sized treatment arms which will receive aldoxorubicin at 50, 100 or 150 mg/m2 by 30-minute intravenous infusion. Because the KS patients in the study have compromised immune systems, the aldoxorubicin dosages administered in the trial are lower than those administered in the Company's clinical testing of aldoxorubicin in patients with soft tissue sarcomas. Patients with advanced KS receive aldoxorubicin on day 1, then every 3 weeks until evidence of tumor progression, unacceptable toxicity or withdrawal of consent. The primary objectives of preliminary efficacy include evaluation of the size, number and nodularity of skin lesions, change in size and number of lung lesions and changes in the number of tumor cells that express the KS virus DNA (Human Herpes Virus 8). The Company is also evaluating the level of aldoxorubicin uptake into lesions. Safety is being assessed through monitoring of adverse events and the ability to remain on assigned treatment. The trial is being conducted at the Louisiana State University Health Sciences Center in New Orleans, LA. Possible additional sites are being considered to expedite enrollment.
Kaposi sarcoma is a cancer that causes lesions (abnormal tissue) to grow in the skin; the mucous membranes lining the mouth, nose, and throat; lymph nodes; or other organs. The lesions are usually purple and are made of cancer cells, new blood vessels, red blood cells, and white blood cells. Kaposi sarcoma is different from other cancers in that lesions may begin in more than one place in the body at the same time. KS remains the most common HIV-associated tumor worldwide. The condition is also endemic in certain parts of Central Africa and Central and Eastern Europe.
The widely used chemotherapeutic agent doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to circulating albumin, the most plentiful protein in the bloodstream. Protein-hungry tumors concentrate albumin, thus increasing the delivery of the linker molecule with the attached doxorubicin to tumour sites. In the acidic environment of the tumour, but not the neutral environment of healthy tissues, doxorubicin is released. This allows for greater doses (3 ½ to 4 times) of doxorubicin to be administered while reducing its toxic side effects. In studies thus far there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 2,000 mg/m2.