A Phase I Dose Finding Study of APO010 in Patients With Solid Tumors

NCT00437736 | Completed Phase 1 DMC

• 2 other identifiers: AP1001S065APO01
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

Two-centre, open label, uncontrolled, dose-finding phase I study, to determine the safety and tolerability of APO010 administered by intravenous bolus injection once per week. It will be the first time this agent will be administered to humans. At lower dose levels, the first cycle duration is 7 weeks. In subsequent cycles, APO010 is administered as 4 weekly doses followed by a two-week drug rest, cycle duration is 6 weeks. Based on preclinical studies of APO010 may cause liver toxicity and a drop in platelets, that recover within 5 days. The main aim of the study is to identify the recommended dose of APO010 for future clinical studies of APO010.

Conditions

Cancer

Keywords

solid tumor; phase I study; dose-escalation

Outcome Measures

Primary Outcomes (1)

• To determine of the maximum tolerated dose (MTD), based upon first cycle APO010-related DLT in patients with solid tumors.

  3 months

Secondary Outcomes (4)

• A description of the frequency and severity of adverse events (AE) based on the NCI-CTC AE v.3.0.

  3 months

• A description of the local toxicity at site of administration by route of administration based on the NCI-Common Terminology Criteria for Adverse Events (NCI-CTCAE v.3.0); the intervention required and by photographic record.

  3 months

• A definition of the proportion of patients with neutralizing antibodies against APO010.

  3 months

• A description of any objective tumor response based on modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria

  3 months

Study Arms (1)

Single arm dose escalation

EXPERIMENTAL

Drug: APO010

Interventions

APO010 DRUG

APO010 starting at 2.5 µg/m² IV on D1, D15, D22 and D29 followed by a two-week drug rest.

Single arm dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological/cytological diagnosis of non-resectable solid tumors for which therapy of proven efficacy does not exist or is no longer effective.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Ongoing toxicity associated with prior anticancer therapy ≤Grade 1 (NCI-CTCAE v.3.0).
• No more than 3 prior chemotherapy lines for advanced disease (not including neo/adjuvant chemotherapy; reintroduced chemotherapy is considered only 1 line, e.g. platinum reintroduction in ovarian cancer). Exceptions must to be discussed with, and agreed by the Co-ordinating Investigator.
• Adequate hematological, liver and renal function, e.g.:
• Hemoglobin ≥9 mg/dl; Absolute Neutrophil Count (ANC) ≥1.5x109/l; platelets ≥100x109/l; normal coagulation factors (INR, PTT, PT).
• Serum bilirubin ≤upper normal limit (UNL); ALT, AST ≤ UNL but ≤ 2.5 x UNL in case of liver metastases; alkaline phosphatase (liver isoenzyme fraction) ≤ UNL or ≤1.5 x UNL of in case liver metastases; albumin within normal limits.
• Creatinine ≤1.5 mg/dl (≤133µmole/l) or calculated creatinine clearance ≥60 ml/min.
• Life expectancy of at least 3 months.
• Capability of understanding the nature of the trial and giving written informed consent.

You may not qualify if:

• Less than 4 weeks since last chemotherapy, radiotherapy or prior investigational therapy. Less than 2 weeks since last hormone or immunotherapy or signal transduction therapy.
• More than 30% liver parenchyma involvement assessed by computed tomography (CT) scan.
• History of hypersensitivity to preparations containing human albumin, and to intravenously administered proteins/peptides/antibodies.
• Active infection.
• Presence of cirrhosis with abnormal liver function test or chronic viral hepatitis.
• Presence of serious cardiac (congestive heart failure, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorder.
• Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study.
• Symptomatic brain metastases, primary brain tumors or leptomeningeal disease.
• Pregnancy or lactation, or unwillingness to use adequate method of birth control

Sponsors & Collaborators

• Valerio Therapeutics: lead

Study Sites (2)

Oncology Institute of Southern Switzerland, Hospital of Bellinzona

Bellinzona, 6500, Switzerland

Location

Multidisciplinary Oncology Center, Cantonal University Hospital of Vaud

Lausanne, 1011, Switzerland

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Mega-Fas-ligand

Study Officials

• Cristiana Sessa, Prof, MD

  Oncology Institute of Southern Switzerland, Bellinzona Hospital, 6500 Bellinzona, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2007
• First Posted: February 21, 2007
• Study Start: February 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: May 1, 2009
• Last Updated: September 17, 2015

Record last verified: 2015-09

Locations

CH (2)