ASA404 in Combination With Carboplatin/Paclitaxel/Cetuximab in Treating Patients With Refractory Solid Tumors

NCT01031212 | Withdrawn Phase 1 DMC

• 2 other identifiers: UCSF-09997H53469-35218
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of an investigational drug called DMXAA (5-6-dimethylxanthenone-4-acetic acid) or ASA404 when given together with carboplatin, paclitaxel and cetuximab to treat patients with refractory solid tumors.

Conditions

Tumors

Keywords

cancer; neoplasms; adult solid tumor; antineoplastic agents

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  During cycle 1 (4 weeks)

Secondary Outcomes (5)

• The number and percentage of subjects experiencing one or more AEs will be summarized by dose cohort, relationship to study drug, and severity

  Within 30 days after study treatment, or until resolution of AE

• Pharmacokinetics of ASA404 in combination with other agents

  48 hours after cycle 1, day 1

• Disease response by RECIST criteria

  until progression

• Assess biological correlates of antitumor activity by measuring serum 5HIAA, VEGF, bFGF, PLGF, sVEGFR2, FGF 23, serum apoptotic markers (M30/M65)

  4 weeks after treatment end

• DNA analysis of FGFR1 and VEGF polymorphism

  4 weeks after treatment ends

Interventions

ASA404 DRUG

Administered intravenously over 20 minutes weekly after chemotherapy

Also known as: 5-6-dimethylxanthenone-4-acetic acid, DMXAA, AS1404

Cetuximab DRUG

Administered at 400mg/m2 over 120 minutes on day -7 and then 250mg/m2 over 60 minutes weekly thereafter

Also known as: Erbitux

Carboplatin DRUG

Administered at fixed dose of AUC 6 intravenously on day 1 of each 3-week cycle

Also known as: Paraplatin

Paclitaxel DRUG

Administered over 3 hours at a fixed dose of 175mg/m2 intravenously on day 1 of each 3-week cycle

Also known as: Taxol

Eligibility Criteria

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

You may qualify if:

• Histological confirmed malignancy of advanced, incurable solid tumor
• Progression following standard therapy, or no acceptable standard treatment options, or eligible if standard therapy consists of a platinum-based doublet
• Measurable or evaluable disease. Measurable disease required for enrollment in dose expansion cohort at MTD
• ECOG 0-2
• Baseline neuropathy grade ≤ 1
• leukocytes \>3,000/mcL
• absolute neutrophil count \>1,500/mcL
• platelets \>100,000/mcL
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) \<1.5 X institutional ULN
• creatinine within 1.5 x normal institutional limits OR creatinine clearance \>60 mL/min/1.73 m2
• Ability to give written informed consent and willingness to comply with requirements of the protocol
• Women of child-bearing potential must have a negative pregnancy test within 14 days of beginning study drug and agree to use an effective method of birth control during treatment and for six months after last dose of study drug
• Male patients whose sexual partners are women of reproductive potential must be surgically sterile or agree to use a double method of contraception during the study and for six months after last dose of study drug. One of method must be a condom
• Patients with known brain metastases should have "stable disease" defined as no growth over a 6 week period after definitive therapy (surgical or RT), and off steroids and anticonvulsive therapy

You may not qualify if:

• Chemotherapy, hormonal therapy or biologic therapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the start of study therapy or not recovered to \< grade 2 from adverse events due to prior agents
• Prior therapy with EGFR inhibitors is permitted
• Patients receiving palliative radiation therapy \<2 weeks earlier. Patients must have recovered from all toxicities of radiation
• Receiving any other investigational agents
• Any severe and/or uncontrolled intercurrent medical conditions or other conditions that could affect participation in the study
• Any of the following cardiac abnormalities: unstable angina pectoris, including Prinzmetal variant angina, New York Heart Association (NYHA) Classification for Congestive Heart Failure Grade III or greater, myocardial infarction or stroke ≤ 12 months prior to study treatment, long QT syndrome, baseline 12 lead ECG QTc of \>450msec per central evaluation, history of sustained ventricular tachycardia, history of ventricular fibrillation or Torsades de Pointes, right bundle branch block and left anterior hemiblock (bifascicular block), bradycardia (\<50 beats per minute)
• Concomitant use of drugs with a risk of causing Torsades de Pointes
• PT/PTT \> 1.5 x ULN
• Receiving full-dose anticoagulation (low-dose warfarin for a central line allowed)
• History of another primary malignancy less than 5 years prior, except non-melanoma skin cancer or cervical cancer in-situ
• Major surgery ≤ 4 weeks prior (requiring general anesthesia or respiratory assistance)(endoscopic exams with diagnostic intent allowed)
• Minor surgery ≤ 2 weeks prior (not requiring general anesthesia or respiratory assistance)
• Insertion of vascular access device allowed
• Not recovered from surgery-related complications
• Systolic BP \>160mmHg and/or diastolic BP \>90mmHg while on medication for hypertension

Sponsors & Collaborators

• University of California, San Francisco: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

vadimezan; Cetuximab; Carboplatin; Paclitaxel

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Sarita Dubey, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 8, 2009
• First Posted: December 14, 2009
• Study Start: January 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2013
• Last Updated: May 13, 2013

Record last verified: 2013-05

Locations

US (1)