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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02923934


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT02923934
Ethics application status
Date submitted
2/10/2016
Date registered
5/10/2016

Titles & IDs
Public title
A Phase II Trial of Ipilimumab and Nivolumab for the Treatment of Rare Cancers
Scientific title
A Phase II Clinical Trial Evaluating Ipilimumab and Nivolumab in Combination for the Treatment of Rare Gastrointestinal, Neuro-Endocrine and Gynaecological Cancers
Secondary ID [1] 0 0
ONJ2016-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastrointestinal Cancer 0 0
Neuroendocrine Tumours 0 0
Malignant Female Reproductive System Neoplasm 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Other cancer types
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Cervical (cervix)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ipilimumab
Treatment: Drugs - Nivolumab

Experimental: Ipilimumab and Nivolumab - All Subjects will be treated with: Nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg concurrently every 3 weeks for 4 doses followed by nivolumab only at 3mg/kg every 2 weeks until progression (up to 48 total doses of nivolumab)


Treatment: Drugs: Ipilimumab
CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) is a key regulator of T cell activity. Ipilimumab is a CTLA-4 immune checkpoint inhibitor that blocks T-cell inhibitory signals induced by the CTLA-4 pathway, increasing the number of tumor reactive T effector cells which mobilize to mount a direct T-cell immune attack against tumor cells. CTLA-4 blockade can also reduce T regulatory cell function, which may lead to an increase in anti-tumor immune response.

Treatment: Drugs: Nivolumab
A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death-1 (PD-1,PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs (antigen presenting cells). This results in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens. Activated PD-1 negatively regulates T-cell activation and and plays a key role in in tumor evasion from host immunity.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To determine the clinical efficacy of the combination treatment of ipilimumab with nivolumab in rare cancers.
Timepoint [1] 0 0
at 12 weeks following randomisation then every 6 weeks until disease progression
Secondary outcome [1] 0 0
To identify whether a common predictive biomarker or immune signature can be identified in responding patients that can occur irrespective of tumour type.
Timepoint [1] 0 0
Pre-dose samples will be collected during the first two cycles (6 weeks/cycle)

Eligibility
Key inclusion criteria
1. Signed Written Informed Consent

* Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
2. Target Population

* Histologically confirmed Upper GI malignancies (Cholangiocarcinoma/ duodenal carcinoma - collect MSI (microsatellite instability) status); Neuroendocrine tumours (inc. pancreatic, bronchial and intestinal carcinoid tumours) and Rare Gynaecological tumours (including but will not be limited to: vaginal or vulval carcinomas, clear cell carcinoma of the ovary, low grade serous ovarian cancer, mixed Mullarian tumours (carcinosarcoma), sarcomas of the female genital tract and granulosa cell tumours).
* Eastern Cooperative Oncology Group (ECOG) performance status of 1
* Prior systemic therapy is permitted if it was completed at least 4 weeks prior to enrolment, and all related adverse events have either returned to baseline or stabilized or subjects are not suitable for, or if declining established standard therapies.
* Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration.
* Measurable disease by CT or MRI per RECIST 1.1 criteria
* Tumour tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses. If an insufficient amount of tumour tissue from an unresectable or metastatic site is available prior to the start of the screening phase, subjects must consent to allow the acquisition of additional tumour tissue for performance of biomarker analyses.
* Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization:

* WBC (white blood cells) > or = to 2000/µL
* Neutrophils > or = to 1500/µL
* Platelets > or = to 100 x103/µL
* Hemoglobin > 9.0 g/dL
* Serum creatinine < or = to 1.5 x ULN or creatinine clearance (CrCl) 40 mL/min (using the Cockcroft-Gault formula)
* AST/ALT (aspartate transaminase/alanine transaminase) < or = to 3 x ULN
* Total Bilirubin < or = to 1.5 x ULN (Upper limit of normal) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL).
* Subject Re-enrolment: This study permits the re-enrolment of a subject that has discontinued the study as a pre-treatment failure (i.e. subject has not been treated) after obtaining agreement from the medical monitor prior to re enrolling a subject. If re-enrolled, the subject must be re-consented.
3. Age and Reproductive Status

* Men and women, > or = to 18 years of age
* Women of childbearing potential (WOCBP) must use method(s) of contraception. WOCBP should therefore use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for Nivolumab to undergo five half lives) after the last dose of investigational drug.
* Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
* Women must not be breastfeeding
* Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1 percent per year. Men that are sexually active with WOCBP must follow instructions for birth control when the half life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 90 days plus the time required for the investigational drug to undergo five half lives. The half life of nivolumab and ipilimumab is up to 25 days and 18 days, respectively. Given the blinded nature of the study, men who are sexually active with WOCBP must continue contraception for 31 weeks (90 days plus the time required for nivolumab to undergo five half lives) after the last dose of investigational drug.
* Women who are not of childbearing potential (i.e. who are postmenopausal or surgically sterile and azoospermic men do not require contraception.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Target Disease Exceptions

* Active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI except where contraindicated in which CT scan is acceptable) evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. Cases should be discussed with the medical monitor. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
2. Medical History and Concurrent Diseases

* Prior combination treatment directed against the PD-1/PDL1 (Programmed Death Ligand 1) axis (anti PD 1, anti PD-L1, anti PD L2), and anti CTLA 4 antibody. Prior monotherapy with these agents or other immune-stimulating/regulating agents is permitted.
* Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
* Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
* Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
* Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
3. Physical and Laboratory Test Findings

* Any positive test result for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
4. Allergies and Adverse Drug Reaction

* History of allergy to study drug components.
* History of severe hypersensitivity reaction to any monoclonal antibody.
5. Sex and Reproductive Status

* WOCBP who are pregnant or breastfeeding
* Women with a positive pregnancy test at enrolment or prior to administration of study medication.
6. Other Exclusion Criteria

* Prisoners or subjects who are involuntarily incarcerated
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/12/2023
Sample size
Target
Accrual to date
Final
120
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Border Medical Oncology Unit - Albury
Recruitment hospital [2] 0 0
Blacktown Hospital - Sydney
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3078 - Heidelberg
Recruitment postcode(s) [5] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Olivia Newton-John Cancer Research Institute
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Oliver Klein, MD
Address 0 0
ONJCRI and Austin Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No plan to share individual participant data


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02923934

Additional trial details provided through ANZCTR
Accrual to date
120
Recruitment state(s)
Funding & Sponsors
Funding source category [1] 66
Government body
Name [1] 66
Department of Health
Address [1] 66
GPO Box 9848 Canberra ACT 2601 Australia
Country [1] 66
Australia
Funding source category [2] 67
Other
Name [2] 67
Investigator sponsored research
Address [2] 67
Bristol Myers-Squibb Nexus Drive Mulgrave
Country [2] 67
Australia
Primary sponsor
Other
Primary sponsor name
Olivia Newton-John Cancer Research Institute
Primary sponsor address
Level 5, ONJ Building
145 Studley Rd
Heidelberg
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 42
Austin Health HREC
Address [1] 42
L8, HSB 145 Studley Rd Heidelberg VIC 3084
Country [1] 42
Australia
Date submitted for ethics approval [1] 42
28/04/2016
Approval date [1] 42
20/09/2016
Ethics approval number [1] 42
HREC/16/Austin/152
 
Public notes

Contacts
Principal investigator
Title 301 0
Dr
Name 301 0
Oliver Klein
Address 301 0
Austin Health Medical Oncology L4, ONJ Building 145 Studley Rd Heidelberg, VIC 3084
Country 301 0
Australia
Phone 301 0
+61394965000
Fax 301 0
Email 301 0
oliver.klein@onjcri.org.au
Contact person for public queries
Title 302 0
Dr
Name 302 0
Jodie Palmer
Address 302 0
L5, ONJCWC, Studley Rd
Country 302 0
Australia
Phone 302 0
+61 3 94963573
Fax 302 0
Email 302 0
trials@onjcri.org.au
Contact person for scientific queries
Title 303 0
Dr
Name 303 0
Oliver Klein
Address 303 0
Austin Health Medical Oncology L4, ONJ Building 145 Studley Rd Heidelberg, VIC 3084
Country 303 0
Australia
Phone 303 0
+61394965000
Fax 303 0
Email 303 0
oliver.klein@onjcri.org.au