Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

All Drugs and Chemicals

Antineoplastic Agents

Liver Extracts

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Sunitinib 50 mg by oral capsule, daily for 4 weeks in every 6 week cycle until progression or unacceptable toxicity.

Sunitinib (SU011248)

Pfizer CT.gov Call Center

The study will consist of two parts. In Part 1 the study will start enrolling 38 patients and then further 25 patients up to a total of 63 eligible patients. If the study gives good results it can be expanded to a total of 160 patients. SU011248 will be administered orally daily for 4 weeks followed by a 2-week rest at a starting dose of 50 mg \[milligrams\] with provision for dose reduction based on tolerability. All patients will receive repeated cycles of SU011248 until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. After discontinuation of treatment, patients will be followed up in order to collect information on further antineoplastic therapy and survival

An International Phase 2 Study Of SU011248 In Patients With Inoperable Liver Cancer

An Open Label International Multi-Center Phase 2 Activity And Safety Study Of SU011248 In Patients With Unresectable Hepatocellular Carcinoma

Number of subjects with best overall response. Complete response (CR)=disappearance of all target lesions. Partial Response (PR)= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. Progressive disease (PD)= ≥ 20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of the longest dimensions since treatment start, or the appearance of ≥ 1 new lesion. Stable disease (SD)=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.

Number of patients with objective response: confirmed CR or confirmed PR according to RECIST. CR was defined as the disappearance of all target lesions. A PR was defined as a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. To be assigned a status of PR or CR, changes in tumor measurements in patients with responding tumors had to have been confirmed by repeat studies that were performed ≥ 4 weeks after the criteria for response were first met.

Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of disease progression or to death due to any cause. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions.

Number of patients with Clinical Benefit Response: confirmed CR, confirmed PR, or SD for at least 12 weeks on study according to RECIST. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. SD=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.

Number of patients with best overall response of PR or SD with duration ≥ 12 weeks. Best overall response was defined as the time from the first documentation of tumor response that was subsequently confirmed to the first documentation of disease progression or to death due to any cause. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. SD=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.

Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause.

Time from the start of study treatment to the first documentation of objective tumor progression.

Time from the date of first dose of study medication to the date of death due to any cause.

Probability of survival 1 year after the first dose of study treatment.

Ctrough = the concentration prior to study drug administration.

Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x \[starting dose/actual dose\]).

Blood samples for the assessment of CECs and circulating CEPs were planned to be obtained for subjects in Part 1 of the study, and for a subset of subjects in Part 2 of the study to complete the angiogenic profile of unresectable hepatocellular carcinoma, in addition to the soluble protein evaluation.

Provision of previously collected tumor paraffin blocks (or at least 5-10 4-micron slides prepared from the paraffin block) for correlative laboratory analysis was optional. For all subjects showing OR on study, it was highly recommended to provide previously collected paraffin blocks (or at least 5-10 4-micron slides prepared from the paraffin block). These samples were to be analyzed for markers that may be associated with tumor proliferation or angiogenesis.

Plasma concentrations of VEGF that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by e nzyme-linked immunosorbent assay (ELISA). Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.

Plasma concentrations of VEGF-C that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.

Plasma concentrations of sVEGFR-2 that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline). Samples below the limit of quantitation and samples with insufficient volume available were excluded.

Plasma concentrations of sVEGFR-3 that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.

Plasma concentrations of sKIT that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.

Pfizer

Director, Clinical Trial Disclosure Group

Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.

50 Milligram (mg) Sunitinib

Age Continuous

Sex: Female, Male

Pfizer ClinicalTrials.gov Call Center

From the Overall ITT population, only 1 subject had Objective Response for evaluation of duration of objective response.

Duration of Objective Response (CR or PR)

Progressive Disease

Not Evaluable

Missing

Intent-to-treat (ITT) population includes all patients enrolled in the study that received at least 1 dose of study medication.

Best Overall Response

Clinical Benefit Response (CR, PR, or SD With Duration ≥12 Weeks)

Best Overall Response of PR or SD With Duration ≥12 Weeks

Progression-Free Survival (Overall ITT)

ITT Child Pugh Class A (assessment of liver function) subject population = subjects enrolled in the study with Child-Pugh Class A that received at least 1 dose of study medication.

Progression-Free Survival (ITT Child Pugh Class A Subject Population)

Time to Tumor Progression (Overall ITT)

Objective Response (CR or PR)

ITT Child Pugh Class A (assessment of liver function) subject population

Time to Tumor Progression (ITT Child Pugh Class A Subject Population)

Overall Survival (Overall ITT)

Overall Survival (ITT Child Pugh Class A Subject Population)

1-Year Survival Probability

Cycle 1, Day 1 (n=37)

Cycle 1, Day 14 (n=32)

Cycle 1, Day 28 (n=29)

Cycle 2, Day 1 (n=25)

Cycle 2, Day 28 (n=19)

Cycle 3, Day 1 (n=16)

Cycle 3, Day 28 (n=16)

Cycle 5, Day 28 (n=12)

Pharmacokinetic (PK) = All subjects enrolled in the study who at least 1 PK sample collected.

Trough Plasma Concentrations (Ctrough) of Sunitinib

Ctrough of SU-012662 (Metabolite of Sunitinib)

Cycle 1, Day 28 (n=28)

Cycle 2, Day 1 (n=14)

Cycle 3, Day 1 (n=8)

Cycle 5, Day 28 (n=11)

Ctrough of Total Drug (Sunitinib + SU-012662)

Cycle 1, Day 14 (n=29)

Cycle 1, Day 28 (n=18)

Cycle 2, Day 1 (n=11)

Cycle 2, Day 28 (n=15)

Cycle 3, Day 1 (n=6)

Cycle 3, Day 28 (n=10)

Cycle 5, Day 28 (n=10)

Dose-Corrected Ctrough of Sunitinib

Cycle 2, Day 1 (n=12)

Cycle 3, Day 1 (n=7)

Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)

Cycle 2, Day 1 (n=13)

Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)

ITT. Blood samples for CECs and CEP cells were collected during the study, but evaluations of these samples were not performed.

Circulating Endothelial Cells (CECs) and Circulating Endothelial Progenitor Cells (CEPs)

ITT. Tumor biopsy results were collected optionally in 5 subjects; however, no evaluations were performed.

Spots Global Cancer Trial Database for liver neoplasms, sunitinib, phase 2