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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02903771




Registration number
NCT02903771
Ethics application status
Date submitted
12/09/2016
Date registered
16/09/2016
Date last updated
21/01/2019

Titles & IDs
Public title
Phase I Study of Cantrixil in Patients With Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer.
Scientific title
Phase I Study of Intra-peritoneal Cantrixil in Patients With Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer.
Secondary ID [1] 0 0
NVGN-002-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Neoplasms 0 0
Fallopian Tube Neoplasms 0 0
Peritoneal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Part A: Dose Escalation of Cantrixil
Treatment: Drugs - Part B: Expansion Cohort of Cantrixil

Experimental: Part A and Part B - Part A (Dose Escalation):
Part A is a Dose Escalation study to determine the Maximum Tolerated Dose of Cantrixil as a monotherapy.
The tolerance of Cantrixil in combination with standard chemotherapy agents will also be examined.
Part B (Expansion Cohort):
An expansion cohort of an additional 12 patients will be recruited at the MTD.


Treatment: Drugs: Part A: Dose Escalation of Cantrixil
Cantrixil will be administered via the intraperitoneal route only. The dose of study drug that each participant will receive will depend on how far the study has progressed when the participant enrols. There are 9 potential doses of Cantrixil, they are 0.06, 0.12, 0.24 (starting dose), 0.6, 1.25, 2.5, 5, 10, or 20 mg/kg. The dose each participant receives will remain the same during the study, unless it needs to be reduced for safety reasons. The dose will not be increased.
Each participant will receive the study drug once a week during the first two cycles; each cycle is 21-days (three weeks); the MTD will be determined during Cycle 1 only. If after two cycles of monotherapy, the patient tolerates Cantrixil adequately, they may continue to receive Cantrixil once a week and will also begin combination chemotherapy for another 6 cycles. Participants will receive no more than 8 cycles of study drug.

Treatment: Drugs: Part B: Expansion Cohort of Cantrixil
Once the MTD has been established, an expansion cohort will be recruited at the MTD. An additional 12 patients will be recruited in this cohort on top of those recruited in Part A at the MTD. These patients will be subjected to the same intervention described in Part A with 2 cycles of monotherapy followed by up to 6 cycles of combination therapy.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Determination of the Maximum Tolerated Dose (MTD) - Determination of the MTD of Cantrixil using standard safety monitoring assessments when administered as a monotherapy.
Timepoint [1] 0 0
During Cycle 1 (21 days)
Primary outcome [2] 0 0
Pharmacokinetic (PK) profile of Cantrixil after intra-peritoneal (IP) administration - Description of the PK of Cantrixil when administered as a monotherapy and in combination with standard chemotherapy agent(s)
Timepoint [2] 0 0
0-24 hours after administration
Secondary outcome [1] 0 0
Time to Progression (TTP) - TTP will be measured as the time from treatment start until objective tumour disease progression as defined by RECIST version 1.1 and/or GCIG criteria, but does not include deaths.
Timepoint [1] 0 0
Baseline to End of Study (maximum 36 weeks)
Secondary outcome [2] 0 0
Time to Paracentesis - The time to paracentesis will be measured as the time from treatment initiation until the next paracentesis event for ascites.
Timepoint [2] 0 0
Baseline to End of Study (maximum 36 weeks)
Secondary outcome [3] 0 0
Volume of Malignant Ascites - The volume of abdominal fluid will be measured by estimating the volume of malignant ascites drained at each paracentesis event.
Timepoint [3] 0 0
Baseline to End of Study (maximum 36 weeks)
Secondary outcome [4] 0 0
Disease Response - Disease response will be measured using RECIST version 1.1 criteria; during Follow-up, response may be also assessed using the Gynecological Cancer Intergroup (GCIG) response criteria that incorporates CA-125 measurements
Timepoint [4] 0 0
Baseline to End of Study (maximum 36 weeks)
Secondary outcome [5] 0 0
CA-125 level - Concentration of CA-125 in peripheral blood will be assayed in local laboratories using locally validated assays at baseline and then weekly during treatment, at the End of Therapy and during Follow-up.
Timepoint [5] 0 0
Baseline to End of Study (maximum 36 weeks)

Eligibility
Key inclusion criteria
1. Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or
primary peritoneal cancer. The original diagnosis must be verified by a histology
report. All histological sub-types and all grades of disease are eligible to
participate; grade, histological sub-type and breast cancer susceptibility gene (BRCA)
status must be recorded at study entry.

2. Patients must be female and at least 18 years old.

3. Patients with malignant ascites are eligible to participate; paracentesis will be
conducted before the administration of Cantrixil. Drainage of the maximum volume of
ascites necessary for symptomatic relief should be performed according to local
standard operating procedures before administration of Cantrixil.

4. Patients must have completed at least two (2) or more prior therapies (including
adjuvant therapy) for their ovarian, Fallopian tube or primary peritoneal cancer prior
to participation in the current study; all prior therapies must be recorded at
baseline. Patients that have received prior intraperitoneal therapy are eligible for
this study.

5. Patients must have platinum-resistant relapsed disease, platinum refractory disease,
or have documented intolerance to platinum therapy. Patients will not be eligible
based on rising CA-125 levels alone, patients must have other clinical symptoms (such
as malignant ascites) or radiological tumour measurements that support disease
recurrence or progression.

6. At least 4 weeks must have passed from any previous therapy and any toxicities from
prior therapies (6 weeks for bevacizumab, nitrosoureas or mitomycin C treatment) must
have resolved to less than or equal to Common Terminology Criteria for Adverse Events
(CTCAE version 4.03) Grade 1 with the exception of alopecia, Grade 2 prior
platinum-therapy related neuropathy and Grade 2 anaemia.

7. Patients must have a performance status of Eastern Cooperative Oncology Group (ECOG) 0
to 2 and, in the Investigator's opinion, be able to complete at least a major part of
the study.

8. Patients must be willing and able to undergo insertion of a port or catheter for
intraperitoneal access; the type of port or catheter used will be recorded.

9. Patients may have measurable or non-measurable disease; disease response and
progression will be measured and assessed according to RECIST version 1.1 criteria
using contrast CT, MRI and CA 125 measurements.

10. Patients must have acceptable hepatic and marrow function as defined below:

- Absolute neutrophil count >1.5 x 109/L

- Platelets >100 x 109/L

- Total bilirubin; <2.5 times the institutional upper limit of normal (ULN)

- Haemoglobin (Hb) of >10 g/dL; patients with Hb >9g/dL will be considered for this
study if they have not received a transfusion or other bone marrow support.
Patients with Hb >10 g/dL that have received a recent transfusion will only be
eligible if there has been a wash-out period of 7 days for rhesus factor and 10
days for platelet transfusions, respectively.

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase
[SGPT]) =2.5 x institutional ULN.

- Serum creatinine <1.5 x ULN

- Prothrombin time (PT) or international normalised ratio (INR) =1.5 x ULN and
activated partial thromboplastin time (aPTT) =1.5 x ULN if not on anticoagulation
treatments.

11. Patients must be willing and able to comply with all study requirements, including
treatment timing and/or nature of required assessments and treatment at designated
study centre.

12. Each participant must be adequately informed about the purpose of the study; potential
benefits and risks; their right to refuse participation or to withdraw consent at any
time; institutional affiliation and potential competing interests of the researcher;
and sources of study funding and have signed and dated a written informed consent
form.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who have had chemotherapy, biologic therapy, immunotherapy, or radiotherapy
within 4 weeks (6 weeks for bevacizumab, nitrosoureas or mitomycin C) prior to
entering the study.

2. Patients must not have had major surgery within 4 weeks prior to screening.

3. Patients may not have received any other investigational medicinal products (IMPs) or
participated in any other interventional clinical research studies within 3 months of
the first Cantrixil administration.

4. Patients receiving any medications or substances that are strong inhibitors or
inducers of cytochrome P450 (CYP)1A2, CYP2B6 and CYP3A4 or those substances with
narrow therapeutic index are not to be enrolled. These compounds are prohibited from
screening until completion of end of therapy or first post-treatment follow-up visit.
For a list of prohibited medications see the University of Indiana Clinical
Pharmacology Department's P450 Drug Interaction Table
(http://medicine.iupui.edu/clinpharm/ddis/main-table/). Note: the use of paclitaxel is
allowed, but only 24 hours after Cantrixil administration.

5. Patients at high risk of bowel perforation are excluded, including but not limited to
any one or more of the following;

- Patients with a recent history (previous 12 months) of bowel obstruction prior to
study entry

- Patients with CT scans that suggest invasion of bowel by tumour

- Patients with symptoms to suggest impending bowel obstruction

- Patients with prior whole abdominal radiotherapy

- Patients with chronic inflammatory bowel diseases such as Crohn's disease or
ulcerative colitis

6. Patients may not have uncontrolled or severe systemic diseases or psychiatric
conditions, which in the treating physician's opinion makes it unsafe for the patient
to participate in the study or would hinder compliance with the protocol. Screening
for chronic conditions is not required.

7. Patients that are pregnant, lactating, or unable to adopt adequate contraception are
excluded. Women of childbearing potential must have a negative pregnancy test within 7
days prior to screening.

8. Patients with a known history of hepatitis B or C.

9. Patients known to have tested positive for human immunodeficiency virus (HIV)

10. Patients with a known hypersensitivity to or serious reaction to benzopyrans are
excluded.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
Westmead Adults Hospital - Westmead
Recruitment hospital [2] 0 0
ICON Cancer Care - South Brisbane
Recruitment hospital [3] 0 0
Flinders Medical Centre - Adelaide
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Oklahoma
Country [2] 0 0
United States of America
State/province [2] 0 0
Rhode Island
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Kazia Therapeutics Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The main purpose of this study is to determine the safety and feasibility of weekly
intra-peritoneal administration of Cantrixil to women with persistent or recurrent ovarian
cancer, Fallopian tube cancer or primary peritoneal cancer. The study also aims to determine
the maximum tolerated dose of Cantrixil in these patients when administered as a monotherapy
or a combination therapy.
Trial website
https://clinicaltrials.gov/show/NCT02903771
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
A/Prof Jermaine (Jim) Coward, BSc, MBBS, PhD, MRCP, FRACP
Address 0 0
ICON Cancer Care, Queensland, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Dr James Garner, MBBS MBA
Address 0 0
Country 0 0
Phone 0 0
+612 94724101
Fax 0 0
Email 0 0
james.garner@kaziatherapeutics.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02903771