Phase Ib Study of Gemcitabine Plus Cisplatin or Carboplatin Plus Dovitinib in Patients With Advanced Solid Tumors

• Status: Terminated
• Trial end date: 2013-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase Ib dose escalation study of dovitinib given in combination with either gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. Patients with advanced solid tumors, for whom treatment with gemcitabine plus cisplatin or carboplatin would otherwise be warranted, will be enrolled. The dose of dovitinib will be escalated in successive cohorts using standard "3+3" dose escalation rules. Patients will continue treatment, in the absence of prohibitive toxicity, until disease progression. The study will define the recommended phase II dose of these combination regimens.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Matthew Galsky
• Collaborator: Novartis
• Treatments: Carboplatin; Cisplatin; Gemcitabine

Criteria

Inclusion Criteria:

• Written informed consent and HIPAA authorization for release of personal health information.

• Age ≥ 18 years at the time of consent.

• Karnofsky Performance Status of ≥ 70%.

• Advanced/metastatic solid tumor for which treatment with gemcitabine plus carboplatin or gemcitabine plus cisplatin would otherwise be warranted.

• Prior treatment with chemotherapy is permitted. Patients must not have received more than three prior chemotherapeutic regimens.

• Adequate organ function as determined by the following laboratory values:

• Hemoglobin (Hgb) ≥ 9 g/dL

• Platelets ≥ 100 x 109/L

• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

• Creatinine of ≤ 1.5 OR Calculated creatinine clearance of ≥ 60 cc/min for the cisplatin cohort.

Calculated creatinine clearance of ≥ 30 cc/min for the carboplatin cohort.

• Bilirubin ≤ 1.5 x ULN

• Aspartate aminotransferase (AST, SGOT) ≤ 1.5 ULN

• Alanine Aminotransferase (ALT, SGPT) < 1.5 ULN

• INR ≤ 1.5 and a PTT within normal limits

• LVEF assessed by 2-D echocardiogram (ECHO) > 50% or lower limit of normal or multiple gated acquisition scan (MUGA) > 45% or lower limit of normal

Exclusion Criteria:

• Prior treatment with more than three prior chemotherapy regimens.

• Has had major surgery within 30 days of starting the study treatment

• Have active CNS metastases.

• No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.

• Prior cancer treatment must be completed at least 30 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxic effects of the regimen.

• Prior radiation therapy must be completed at least 30 days prior to being registered for protocol therapy.

• Pregnant or breastfeeding.

• Clinically significant infections as judged by the treating investigator.

• Impaired cardiac function or clinically significant cardiac diseases

• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

• Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin

• Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception.

• Fertile males not willing to use contraception