Phase II Study of Best Support Care (BSC) Plus ZD6474(Vandetanib) in Patients With Inoperable Hepatocellular Carcinoma (HCC)

NCT00508001 | Completed Phase 2 Results

• 1 other identifier: D4200C00072
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multi-centre, phase II study to assess the efficacy and safety of ZD6474 in patients with Child-Pugh class A, inoperable HCC. This study comprises 2 phases, the primary treatment phase and the secondary treatment phase. The primary treatment phase is a randomised, double-blind, parallel-group phase II study to assess the efficacy and safety of ZD6474 300 mg plus best support care (BSC), ZD6474 100 mg plus BSC, and placebo plus BSC. The secondary treatment phase is an open-label expanded access program of ZD6474. In the primary treatment phase, patients will be randomised in a 1:1:1 ratio to receive ZD6474 300 mg plus BSC, ZD6474 100 mg plus BSC, or placebo plus BSC, respectively. Randomisation will be stratified on the basis of Cancer of the Liver Italian Programme (CLIP) tumour staging (CLIP score 0-2 versus 3-4). The primary treatment will continue until objective disease progression, according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, or until patients meet any other withdrawal or discontinuation criteria.The primary endpoint is tumour stabilisation rate, and the secondary endpoints are objective response rate, progression-free survival, and overall survival. The purpose of the secondary treatment phase is to expand the access of ZD6474 so that every patient who is enrolled into this study can have the chance to receive the active medicine.Once an individual patient has progressive disease in the primary treatment phase, the blind will be broken for this patient. If this patient is in the ZD6474 100 mg arm or placebo arm, the patient will be offered the secondary treatment with ZD6474 300 mg per day. If this patient is randomised to the ZD6474 300 mg arm, the study medication will be discontinued unless the patient wishes to remain the treatment, and the patient is to be followed up for survival.

Conditions

Carcinoma, Hepatocellular

Keywords

Hepatocellular carcinoma; Advanced solid, malignant tumour

Outcome Measures

Primary Outcomes (1)

• Tumour Stabilisation Rate

  Tumour stabilisation rate calculated as percentage of patients with best objective tumour response (Complete Response, Partial Response or Stable Disease) for \>=16 weeks based on Response Evaluation Criteria in Solid Tumours (RECIST). Complete Response - Disappearance of all target lesions; Partial Response - \>=30% decrease in the sum of longest diameter of target lesions; Progressive Disease - \>=20% increase in the sum of longest diameter of target lesions; Stable Disease - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  After 16 weeks of treatment.

Secondary Outcomes (3)

• Objective Response Rate

  After 16 weeks of treatment.

• Progression-free Survival

  from the date of randomisation to the date of documented disease progression or death for any cause

• Overall Survival

  assessed up to 360 days

Study Arms (3)

1

PLACEBO COMPARATOR

Best Supportive Care + Placebo

Drug: Best Supportive Care

2

EXPERIMENTAL

Best Supportive Care + ZD6474 100 mg

Drug: Vandetanib

3

EXPERIMENTAL

Best Supportive Care + ZD6474 300 mg

Drug: Vandetanib

Interventions

Vandetanib DRUG

ZD6474 300mg

Also known as: Zactima, ZD6474

3

Best Supportive Care DRUG

Placebo + Best Supportive Care

1

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and provide informed consent
• Histologically diagnosed HCC, OR clinically diagnosed HCC for patients with difficulty in obtaining histological diagnosis. A clinically diagnosed HCC should fulfil ALL the criteria below.
• Chronic hepatitis B or C and/or evidence of liver cirrhosis
• Presence of hepatic tumour(s) with image findings (sonography, CT scan, or MRI scan) compatible with HCC, and no evidence of other gastrointestinal tumours
• A persistent elevation of serum a-fetoprotein level \>= 400 ng/ml without any evidence of an existing a-fetoprotein-secreting germ cell tumour
• Locally advanced (for example, portal vein invasion, multiple nodules, or nodules in both lobes) or metastatic HCC with at least one measurable lesion by RECIST criteria that meets ANY the criteria below:
• HCC not suitable to receive local therapy, including surgical resection, percutaneous ethanol injection (PEI), or transarterial chemo-embolization (TACE)
• Disease recurred or was refractory to previous local therapy
• Patients refused local therapy
• At least one measurable lesion by RECIST criteria. Tumour lesions treated previously with local radiotherapy, percutaneous ethanol injection, radiofrequency ablation, or transarterial embolization are NOT considered measurable.
• If they completed percutaneous ethanol injection, radiofrequency ablation, transarterial embolization, or cryotherapy at least 4 weeks prior to enrollment, patients must have subsequent progression or recurrence with at least one new measurable lesion that has not been treated with any local procedure.
• Karnofsky performance status \>= 70
• Life expectancy \>= 2 months
• Child-Pugh class A liver function
• Adequate bone marrow reserve, defined as white blood cell count \>= 3,000/ml, and platelet count \>= 75,000/ml

You may not qualify if:

• Receiving concurrent anti-cancer therapy for HCC, which includes local therapy, chemotherapy, or other experimental therapy
• Prior systemic cytotoxic chemotherapy
• Prior transarterial chemo-embolization (TACE) or hepatic arterial infusion (HAI), with any of the following conditions for those patients who have any target lesions in the liver:
• More than 5 TACE or HAI sessions undergone prior to enrollment
• The cumulative doses of doxorubicin \> 120 mg/m2, mitomycin-C \> 24 mg/m2, cisplatin \> 120 mg/m2, or 5-fluorouracil \> 2400 mg/m2
• Details of the TACE or HAI regimens are not available in the chart
• (Note: The number of sessions of prior TACE or HAI will not be limited for patients who have no target lesion in the liver).
• Local treatment including radiotherapy (except palliative radiotherapy), percutaneous ethanol injection, radiofrequency ablation, transarterial embolization, or cryotherapy completed within 4 weeks prior to enrollment
• Prior therapy targeting VEGF or EGF signalling pathways, including but not limited to bevacizumab, cetuximab, gefitinib, erlotinib, or sorafenib.
• Prior thalidomide therapy is not allowed but for patients who stop thalidomide due to intolerability and meet either one of following condition can be included:
• Patients who took thalidomide for no more than \<= 3 days before enrolment
• Patients who took thalidomide for \> 3 days but \<= 14 days and are confirmed clinically not responding to thalidomide. 14 days washout period is needed before enrolment.
• Laboratory results:
• Serum potassium less than 4.0 mmol/L despite supplementation
• Serum calcium (ionized or adjusted for albumin) or magnesium out of their normal ranges despite supplementation

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (3)

Research Site

Tainan, Taiwan

Location

Research Site

Taipei, Taiwan

Location

Research Site

Taoyuan District, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neoplasms

Interventions

vandetanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Study Director Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2007
• First Posted: July 27, 2007
• Study Start: July 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: June 1, 2009
• Last Updated: October 10, 2016
• Results First Posted: July 17, 2012

Record last verified: 2016-08

Locations

TW (3)