CytRx Corporation, a biopharmaceutical research and development company specializing in oncology, announced the initiation of enrollment in an open-label phase 1b clinical trial designed to investigate the preliminary safety and activity of aldoxorubicin plus gemcitabine in subjects with metastatic solid tumours. Aldoxorubicin is CytRx's modified version of the widely-used chemotherapeutic agent, doxorubicin.

The phase 1b clinical trial will be conducted at the Virginia G. Piper Cancer Center in Scottsdale, AZ, the Samuel Oschin Cancer Center at Cedars Sinai Medical Center, Los Angeles, CA, and the Sarcoma Oncology Center in Santa Monica, CA. The clinical trial is expected to enroll up to 30 male and female patients between the ages of 15 and 80 with advanced, unresectable, metastatic solid tumours that have either relapsed or were refractory to treatment with at least one prior chemotherapy or immunotherapy regimen and for which no standard approved therapy exists.  The company expects to complete enrollment by the third quarter of 2015.

"Initiation of clinical development of aldoxorubicin in combination with gemcitabine for the treatment of metastatic solid tumours represents a potentially significant expansion of our aldoxorubicin franchise in cancer treatment," said CytRx CEO Steven A. Kriegsman. "The start of this combination chemotherapy with aldoxorubicin will allow our testing to move into a variety of new tumours such as pancreatic and ovarian cancers as well as haematological malignancies."

For this clinical trial, aldoxorubicin will be administered at escalating doses by intravenous infusion (IVI) on Day 1 every 21 days plus 900 mg/m2 gemcitabine on Days 1 and 8 every 21 days until disease progression, unacceptable toxicity or the patient withdraws consent.  The primary objective of the trial is to determine the preliminary safety of administration of aldoxorubicin in combination with gemcitabine in subjects with metastatic solid tumours as measured by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, vital signs, echocardiograms (ECHO) or multiple-gated acquisition (MUGA) scans, electrocardiogram (ECG) results, and weight. The secondary objective of the trial is to evaluate the activity of aldoxorubicin in combination with gemcitabine in this population, assessed by overall response rate (ORR), progression-free survival (PFS), and PFS at 4 and 6 months.

Aldoxorubicin is also currently being studied in a pivotal global phase 3 clinical trial evaluating the efficacy and safety of aldoxorubicin as a second-line treatment for patients with STS under a Special Protocol Assessment with the FDA.  CytRx is also evaluating aldoxorubicin in two phase 2 clinical trials, one in patients with late-stage glioblastoma (GBM) and the other in HIV-related Kaposi's sarcoma, a global phase 2b clinical trial in patients with relapsed small cell lung cancer, and in a phase 1b trial in combination with ifosfamide in patients with soft tissue sarcoma.

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 tumours 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.