ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12616000440426

Ethics application status

Approved

Date submitted

1/04/2016

Date registered

6/04/2016

Date last updated

24/03/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

Decitabine/carboplatin combination treatment protocol for metastatic melanoma

Scientific title

Pilot Early phase II study of Decitabine and Carboplatin in patients with advanced melanoma

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

PRIME001

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Metastatic melanoma

Condition category

Condition code

Cancer

Malignant melanoma

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

First month- Decitabine 7mg/m2 intravenous infusion (IVI)/day for 5 days (D1-D5) followed by Carboplatin Area under the curve (AUC) 5 as per the Calvert formula, IVI on D8; Week 3 and Week 4- no treatment.

Second month- repeat above starting at Week 5, Day 29.

All doses administered and logged on site by study staff.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Tumour biopsy will be used for the composite outcome of DNA methylation (whole genome bisulfite sequencing and ELISA assay), XPC mRNA and XPC protein levels. Statistically significant differences in methylation and XPC levels will be tested before and after treatment using paired t-test with Bonferroni correction.

Timepoint [1]

Week 9 post commencement of treatment

Primary outcome [2]

Tumour biopsy will be used for immunohistochemistry to assess the composite outcome of immune-response markers: CD4 and CD8 inside tumour, number of tumour cells with PDL1 expression, CD8 with PDL1 expression, CD8 with CD45RO expression, CD8 with granzyme B, TIM3, perforin as described in Tumeh et al. 2015. Blood collected will be tested for immune activation profile and INF gamma signature. All data will be inccluded for composite outcome and will be tested before and after treatment using paired t-test with Bonferroni correction.

Timepoint [2]

9 weeks post commencement of treatment

Secondary outcome [1]

Quantify response rate (RR) using RECIST 1.1 criteria at completion of 2 cycles. This data will be used to calculate sample size for larger Phase II study.

Timepoint [1]

9 weeks post commencement of treatment

Eligibility

Key inclusion criteria

1. Age>= 18 years
2. Before study enrolment written informed consent to participate in the trial must be given according to ICH/GCP and national/local regulations
3. Resistance to all approved treatments for melanoma
4. Tumour material is mandatory- tumour tissue selected must not be previously irradiated; treatment should start only after complete wound healing from surgery
5. Disease status before first treatment should be documented by full CT scan of brain, chest, abdo and pelvis and PET scan and MRI brain if indicated
6. BRAF mutation status
7. ECOG Performance Status 0,1,2

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. mucosal or ocular melanoma
2. CNS metastases
3. Patient demonstrates inadequate organ function- hematologic, hepatic and renal
4. History of pneumonitis, interstitial lung disease, inflammatory bowel disease or active auto-immune disease that required systemic treatment in past 2 years (with use of disease modifying agents, corticosteroids or immune suppressive drugs)
5. History of immune related toxicity to previous immunotherapy of grade 2 or higher except endocrinology related toxicity that is treated and stable and on replacement therapy for adrenal, pituitary or thyroid deficiency (thyroxine, insulin or physiologic corticosteroid therapy allowed)
6. Diagnosis of immunodeficiency
7. Known history of HIV; active Hep B/C
8. Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
9. Patients who received treatment with live vaccines within 30 days prior to first dose of study medication
10. Patient is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used and investigation device within 4 week prior to first dose of treatment
11. History of hematologic or primary solid tumour malignancy, unless no evidence of that disease for 5 years
12. Pregnancy and Contraception- Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first dose of study treatment
13. Female patients who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 120 days after the last dose of the study drug

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

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 / Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Statistically significant differences in methylation and XPC levels will be tested before and after treatment using paired t-test with Bonferroni correction. Response rate (RR) using RECIST 1.1 criteria will be quantified at completion of 2 cycles. This data will be used to calculate sample size for larger Phase II study.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/06/2016

Actual

21/02/2017

Date of last participant enrolment

Anticipated

31/12/2017

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Calvary Mater Newcastle - Waratah

Recruitment postcode(s) [1]

2298 - Waratah

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Ramaciotti Foundation

Address [1]

Perpetual Trustees
GPO Box 4171, Sydney NSW 2001

Country [1]

Australia

Primary sponsor type

University

Name

University of Newcastle

Address

University Dr
Callaghan, NSW 2308

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Hunter New England Human Research Ethics Committee

Ethics committee address [1]

Research Ethics and Governance Unit
Locked bag 1, New Lambton, NSW, 2305

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

18/12/2015

Approval date [1]

16/03/2016

Ethics approval number [1]

15/12/16/3.08

Summary

Brief summary

The primary purpose of this pilot trial is to examine the efficacy of decitabine in combination with carboplatin for the treatment of metastatic melanoma. 
Who is it for? 
You may be eligible to participate in this trial if you are aged 18 or over, and have been diagnosed with metastatic melanoma which has been resistant to all previous treatments. Study details 
All participants enrolled in this trial will receive combination therapy with two chemotherapy agents, decitabine and carboplatin, according to the following treatment regime. On days 1-5, patients will receive a daily intravenous infusion of decitabine, followed by a single infusion of carboplatin on day 8. There will then be no treatment administered for the remainder of the cycle, until the regime is repeated starting on day 29. 
Researchers will perform tests on blood and tumour biopsy samples to examine the efficacy of the treatment in altering tumour cells so that they are more vulnerable to the immune system, and thus treating the cancer. It is hoped that information from this trial will provide preliminary information on the efficacy of decitabine in combination with carboplatin for the treatment of metastatic melanoma, and provide data to inform a larger clinical trial of this therapy.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Andre van der Westhuizen

Address

Department of Medical Oncology
Calvary Mater hospital
2 Edith Street
Waratah NSW
2298

Country

Australia

Phone

+61249211561

Fax

[email protected]

Contact person for public queries

Name

Nikola Bowden

Address

Hunter Medical Research Institute
c/o - University Dr
Callaghan NSW 2308

Country

Australia

Phone

+61240420277

Fax

[email protected]

Contact person for scientific queries

Name

Nikola Bowden

Address

Hunter Medical Research Institute
c/o - University Dr
Callaghan NSW 2308

Country

New Zealand

Phone

+61240420277

Fax

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		van der Westhuizen et al. Sequential Decitabine an... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Pilot early phase II study of decitabine and carboplatin in patients with advanced melanoma	2020	https://doi.org/10.1097/md.0000000000020705

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically