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

This study has been withdrawn prior to enrollment.
(The investigator has left the institution (UCSF) prior to study start-up)
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by:
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01031212
First received: December 8, 2009
Last updated: May 9, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Tumors
Drug: ASA404
Drug: Cetuximab
Drug: Carboplatin
Drug: Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of ASA 404 in Combination With Carboplatin/Paclitaxel/Cetuximab in Patients With Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: During cycle 1 (4 weeks) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The number and percentage of subjects experiencing one or more AEs will be summarized by dose cohort, relationship to study drug, and severity [ Time Frame: Within 30 days after study treatment, or until resolution of AE ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of ASA404 in combination with other agents [ Time Frame: 48 hours after cycle 1, day 1 ] [ Designated as safety issue: No ]
  • Disease response by RECIST criteria [ Time Frame: until progression ] [ Designated as safety issue: No ]
  • Assess biological correlates of antitumor activity by measuring serum 5HIAA, VEGF, bFGF, PLGF, sVEGFR2, FGF 23, serum apoptotic markers (M30/M65) [ Time Frame: 4 weeks after treatment end ] [ Designated as safety issue: No ]
  • DNA analysis of FGFR1 and VEGF polymorphism [ Time Frame: 4 weeks after treatment ends ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: January 2010
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ASA404
    Administered intravenously over 20 minutes weekly after chemotherapy
    Other Names:
    • 5-6-dimethylxanthenone-4-acetic acid
    • DMXAA
    • AS1404
    Drug: Cetuximab
    Administered at 400mg/m2 over 120 minutes on day -7 and then 250mg/m2 over 60 minutes weekly thereafter
    Other Name: Erbitux
    Drug: Carboplatin
    Administered at fixed dose of AUC 6 intravenously on day 1 of each 3-week cycle
    Other Name: Paraplatin
    Drug: Paclitaxel
    Administered over 3 hours at a fixed dose of 175mg/m2 intravenously on day 1 of each 3-week cycle
    Other Name: Taxol
Detailed Description:

Phase I 3+3 dose escalation design in patients with solid tumors who have been previously treated with chemotherapy or for whom no standard treatment options exist. Carboplatin, paclitaxel and cetuximab will be administered in standard doses. The dose of ASA404 will be escalated under predefined levels. One treatment cycle constitutes 3 weeks. A minimum of 3 patients will be entered at each treatment level, to be expanded to 6 subjects if dose limiting toxicities (DLT) are observed. If no more than one in six patients has DLT, additional patients will be enrolled at a higher dose. Once a maximum tolerated dose (MTD) has been established, the tolerability of this dose will be tested in a total of 12 patients. The anticipated sample size is 18-24 patients.

Carboplatin and paclitaxel are chosen as the chemotherapy back bone since they are commonly used in combination in multiple tumors. Cetuximab has been chosen as the EGFR inhibitor because the combination of platinum based therapy with cetuximab is effective in lung and head and neck cancers. In addition the safety and activity of carboplatin/paclitaxel with ASA 404 has already been demonstrated. A weekly schedule of ASA is chosen because 1) the safety of the weekly schedule has been tested 2) preclinical studies confirm enhanced activity with frequent administration 3) provides an opportunity to evaluate the safety and pharmacokinetics of ASA 404 with weekly cetuximab.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Hemoptysis associated with chest malignancy <4 weeks (>1 teaspoon)
  • History of hypersensitivity reactions to TAXOL or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil)
  • History of severe allergic reactions to cisplatin or other platinum-containing compounds
  • History of acute hemorrhagic events requiring hospital admission or blood transfusion
  • Pregnant or lactating women
  • Fertile women and men not willing to comply with birth control instructions
  • Any condition that compromises compliance with objectives and procedures of this protocol, as judged by the principal investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01031212

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Novartis Pharmaceuticals
Investigators
Principal Investigator: Sarita Dubey, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: Sarita Dubey, MD, University of California, San Franciso
ClinicalTrials.gov Identifier: NCT01031212     History of Changes
Other Study ID Numbers: UCSF-09997, H53469-35218
Study First Received: December 8, 2009
Last Updated: May 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
cancer
neoplasms
adult solid tumor
antineoplastic agents

Additional relevant MeSH terms:
Neoplasms
Paclitaxel
Cetuximab
Vadimezan
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014