Study of Anti-tumour Effects and Safety of Prolarix™ in Hepatocellular Carcinoma

• Sponsor: BTG International Inc. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00746590
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 11
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This an open-label study designed to evaluate the anti-tumour activity and safety of Prolarix in subjects with advanced hepatocellular carcinoma.

Prolarix is a chemotherapy comprised of tretazicar as prodrug and caricotamide as co-substrate for the endogenous enzyme, NQO2.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Prolarix (tretazicar co-administered with caricotamide)	Phase 2

Detailed Description

The primary objective of this study is to evaluate the anti-tumour effects of treatment with Prolarix in subjects with advanced HCC (Child-Pugh A and B only).

All subjects will receive an IV infusion of Prolarix once every 21 days until disease progression is observed.

Subjects will have CT scans for tumour measurements before starting treatment with Prolarix and every 6 weeks until disease progression.

Subjects will undergo evaluation for safety (adverse events, vital signs, clinical laboratory measurements, weight, ECG) every 21 days until disease progression.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of the Anti-tumour Activity and Safety of Prolarix™ in Hepatocellular Carcinoma (HCC)
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Prolarix (tretazicar co-administered with caricotamide); Prolarix (26.6 mg/m2 tretazicar co-administered with 200 mg/m2 caricotamide) administered intravenously every 21 days until disease progression; Other Names: Prolarix

Outcome Measures

Primary Outcome Measures

1. Overall Best Tumor Response Rate (Proportion of Subjects With Complete or Partial Response) as Defined by Modified RECIST [every 6 weeks until progression]

Secondary Outcome Measures

1. Disease Control Rate Defined as the Proportion of Subjects With Either Complete or Partial Response or Stable Disease [Approximately 12 weeks or more after first treatment with Prolarix]

2. Time to Tumour Progression [Every 3 weeks until progression]

3. Post-treatment Changes in the Amount of Contrast-enhancing and Non-contrast-enhancing Tumour [Every 6 weeks until progression]

4. Changes in Alpha Fetoprotein [Baseline, every 3 weeks until progression]

5. Adverse Events [Until progression]

6. Changes in Laboratory Measurements [Baseline and every 3 weeks until progression]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject must be at least 18 years of age.

• Subject must have a histologic or cytologic diagnosis of HCC and be considered unsuitable for resection or other potentially curative options (eg, liver transplant, curative radiofrequency ablation).

• Subject must have a measurable lesion by RECIST on CT scan in at least one site which has not received radiation or any other local therapy [eg, transcatheter arterial chemoembolisation (TACE), radiofrequency ablation, local injection]. (Note: Subjects who have received local therapies will be allowed to participate, provided that they have a target lesion which has not been subjected to local therapy. Subjects who have received TACE must have a target lesion outside of the vascular territory subjected to chemoembolisation.)

• Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.

• Subject has had no other active malignancy within the past three years [other than non melanomatous skin cancer or carcinoma in situ (CIS) of the breast, bladder, or uterine cervix. Subjects with Ta (non-invasive papillary carcinoma) or Tis (sessile carcinoma in situ) bladder cancer are allowed].

• Subject has a minimum life expectancy of at least three months as determined by the investigator.

• Subject has adequate bone marrow function (ie, haemoglobin ≥9 g/dL, granulocytes ≥1500/mm3, platelets ≥75,000/mm3).

• Prothrombin time (PT)-international normalised ratio (INR) ≤2.3 or PT ≤6 seconds above control. (Note: Subjects who are being therapeutically anticoagulated with an agent such as warfarin or heparin will be allowed to participate provided that their INR is between 2.0 and 3.0.

• Subject has adequate renal function (ie, serum creatinine is normal or calculated creatinine clearance is ≥60 mL/min).

• Subject has adequate hepatic function (ie, bilirubin ≤2x upper limit of normal (ULN); AST ALT, and alkaline phosphatase ≤5xULN). (Also see exclusion for Child-Pugh class C below).

• Male subjects and females of childbearing potential must agree to use an adequate method of contraception from the time of initiation of treatment through study participation and for 3 months after release from the study.

• Subject is able to give informed consent.

Exclusion Criteria:

• Any prior or current systemic pharmacotherapy for HCC (cytotoxic, targeted or biologic). (Note: TACE is not considered to be systemic pharmacotherapy for the purpose of this study).

• Subject has an absolute contraindication to receiving CT contrast media. (Note: Subjects with a history of minor contrast reactions may be pre-medicated prior to contrast administration in accordance with local or institutional practice).

• Subject has Child-Pugh Class C hepatic impairment.

• Subject has received an investigational drug within 30 days of enrolment in the study.

• Females of childbearing potential unless using adequate contraception.

• Pregnant or lactating females.

• Major variceal bleeding in the last 30 days.

• Subjects with a known history of human immunodeficiency virus (HIV) infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200

Sponsors and Collaborators

• BTG International Inc.

Investigators

• Study Director: Claire Daugherty, MS, BTG International Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BTG International Inc.
• ClinicalTrials.gov Identifier: NCT00746590
• Other Study ID Numbers: PR003-CLN-pro001
• First Posted: Sep 4, 2008
• Last Update Posted: Jul 21, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by BTG International Inc.: hepatocellular carcinoma; liver cancer; Prolarix; tretazicar; caricotamide; Phase 2; tumor; chemotherapy
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Tretazicar

Study Results

Participant Flow

Arm/Group Title	Prolarix Treatment Group
Arm/Group Description	Prolarix (tretazicar co-administered with caricotamide): Prolarix (26.6 mg/m2 tretazicar co-administered with 200 mg/m2 caricotamide) administered intravenously every 21 days until disease progression
Period Title: Overall Study
STARTED	1
COMPLETED	0
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Prolarix Treatment Group
Arm/Group Description	Prolarix (tretazicar co-administered with caricotamide): Prolarix (26.6 mg/m2 tretazicar co-administered with 200 mg/m2 caricotamide) administered intravenously every 21 days until disease progression
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%

Outcome Measures

1. Primary Outcome

Title	Overall Best Tumor Response Rate (Proportion of Subjects With Complete or Partial Response) as Defined by Modified RECIST
Time Frame	every 6 weeks until progression

Outcome Measure Data

Analysis Population Description

Study was terminated prematurely after only 1 patient was enrolled. The patient died one month after the initial dose of Prolarix, but his death was unrelated to Prolarix administration.

Arm/Group Title	Prolarix Group
Arm/Group Description	Prolarix (tretazicar co-administered with caricotamide): Prolarix (26.6 mg/m2 tretazicar co-administered with 200 mg/m2 caricotamide) administered intravenously every 21 days until disease progression
Measure Participants	1
Number [Proportion of patients]	NA

2. Secondary Outcome

Title	Disease Control Rate Defined as the Proportion of Subjects With Either Complete or Partial Response or Stable Disease
Time Frame	Approximately 12 weeks or more after first treatment with Prolarix

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Time to Tumour Progression
Time Frame	Every 3 weeks until progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Post-treatment Changes in the Amount of Contrast-enhancing and Non-contrast-enhancing Tumour
Time Frame	Every 6 weeks until progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Changes in Alpha Fetoprotein
Time Frame	Baseline, every 3 weeks until progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Adverse Events
Time Frame	Until progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Changes in Laboratory Measurements
Time Frame	Baseline and every 3 weeks until progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From date of enrollment until the date of death from any cause, assessed every 21 days, up to 1 month.
Adverse Event Reporting Description	Study was terminated prematurely - the one patient who enrolled before termination died after their initial dose. This was not related to Prolarix administration. Other (Not Including Serious) Adverse Events were not monitored/assessed.
Arm/Group Title	Prolarix Treatment Group
Arm/Group Description	Prolarix (tretazicar co-administered with caricotamide): Prolarix (26.6 mg/m2 tretazicar co-administered with 200 mg/m2 caricotamide) administered intravenously every 21 days until disease progression
All Cause Mortality
	Prolarix Treatment Group
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Prolarix Treatment Group
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Gastrointestinal disorders
GI toxicity	1/1 (100%)	1
Other (Not Including Serious) Adverse Events
	Prolarix Treatment Group
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.