Trial to investigate whether the addition of nivolumab or nivolumab and ipilimuab to rucaparib improves effectiveness, compared with rucaparib alone, in patients with relapsed ovarian cancer.

Phase 1

• Conditions: High grade serous ovarian cancer (includes histologically identical fallopian tube and primary peritoneal cancers and high grade G3 endometrioid histological subtypes); MedDRA version: 20.0 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004780-13-GB
• Lead Sponsor: HS Greater Glasgow & Clyde

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-20
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 252

Inclusion Criteria

- Age =16 yrs
- Written informed consent
- Histologically confirmed high-grade serous or Grade 3 endometrioid relapsed (as defined by RECIST v1.1) epithelial ovarian, fallopian tube, or primary peritoneal cancer:
If mixed histology >50% of the primary tumour must be confirmed to be high-grade serous or endometrioid upon review by local pathology with <50% being ‘other’, generally carcinosarcoma
Patients with high grade ovarian cancer histology of other than serous or endometrioid are also eligible if they are already known to harbour a deleterious germline or somatic BRCA1/2 mutation
NB patients who have an original diagnosis based on cytology only will not be eligible for trial entry unless a biopsy confirming criteria above is performed
- Received =1 prior platinum containing chemotherapy regimen(s).Patients can have had up to 3 prior lines (including primary therapy) of therapy for ovarian cancer. Agents administered in the maintenance setting will not be counted as a separate regimen but these must have been stopped at least 28 days prior to trial treatment. Hormonal agents (e.g. tamoxifen, letrozole, etc.), anti-angiogenic agents (e.g. bevacizumab, pazopanib, cediranib, etc.) and other non-chemotherapy agents will not be counted as a chemotherapy regimen but must have been stopped at least 28 days prior to trial treatment. No previous PARP inhibitor, anti-PD-1 or anti-PDL-1 or CTLA4 therapy.
- Had documented treatment-free interval of =3 - <12 months following the last chemotherapy regimen received. These time points are defined as time between Day 1 last cycle (this does not have to be a platinum but could be single agent liposomal doxorubicin or weekly taxol) and RECIST evaluable disease progression
-Has documented platinum free interval of =3 - <12 months from last platinum containing regimen. These time points are defined as time between Day 1 last cycle and first subsequent RECIST evaluable disease progression.
- RECIST evaluable disease (by RECIST criteria v1.1). Patients with CA125 progression in the absence of RECIST measurable disease will NOT be eligible
- Already known to have a deleterious germline or somatic BRCA1/2 mutation (central confirmation still required)OR be gBRCAwt LoHHIGH as confirmed by the central laboratory (Foundation Medicine)
NB: Tissue from BRCA mutant patients already identified locally will be required for confirmation. Sufficient archival formalin-fixed paraffin-embedded (FFPE) tumour tissue of adequate quality (see below) must be available for the central laboratory testing. Cytospin blocks from ascites are not acceptable. To be acceptable for Foundation Medicine testing, tumour tissue must be the most recently obtained specimen with at least 30% tumour content, and a minimum of 80% nucleated cellular content. In the event that archival tumour tissue is not available a screening biopsy sample must be collected and provided to the central laboratory
- Willingness to undergo mandatory biopsy pre cycle1 day1 (where technically feasible)(target lesions (RECIST criteria v1.1) should be avoided if possible).Patient who do not have disease amenable to biopsy are exempt from the biopsy provided all other inclusion criteria are met, they must have archival tumour tissue available for FM testing

Exclusion Criteria

- Prior chemotherapy, biological therapy, radiation therapy, hormonal anti-cancer therapy, immunotherapy, other anticancer agents within 28 days of starting trial treatment (does not include palliative radiotherapy at focal sites which cannot be used as measurable RECIST target sites). Treatment with any other investigational agent within the preceding 4 weeks or within 5 half-lives of the investigational agent, whichever is longer.
- Any prior PARP inhibitor, anti PD-1 or anti PD-L1, anti-PD-L2, anti-CD137, or cytotoxic T lymphocyte-associated antigen 4 (CTLA4) antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
- Pregnant or lactating
- Women of childbearing age and reproductive potential who are not willing, or their male partners are not willing, to use two highly effective forms of contraception.
- With the exception of alopecia and stable peripheral neuropathy from previous taxanes, any unresolved toxicities from prior chemotherapy should be no greater than CTCAE G1 at time of starting trial treatment
- Major surgery within 3weeks or minor surgery within 5days of trial entry (excluding placement of vascular access devices)
- Spinal cord compression, known leptomeningeal involvement or brain metastases, unless treated and stable off steroids for at least 4 weeks prior to randomization
- Warfarin is not permitted.Anticoagulation with low molecular weight heparin and anti Factor X is allowed. Patients who have a new diagnosis of deep vein thrombosis or pulmonary embolism within 2 weeks of randomisation are permitted if clinically stable on a therapeutic dose of LMWH or anti-Factor X.
- Any haemopoietic growth factors (e.g G-CSF, GM-CSF, erythropoeitin) and blood/platelet transfusions within 2weeks prior to randomization or patients requiring regular blood transfusions (e.g 2 or more times in the 4weeks prior to first dose of trial drug),granulocyte colony-stimulating factor,or platelet transfusions.
- Hospitalization for bowel obstruction within 3months prior to randomization
- Any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
- Has a known diagnosis of immunodeficiency, active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (screening for these is not required). Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7days prior to first dose of trial treatment. Includes prior organ transplantation including allogenic stem-cell transplant. The following are exceptions to this exclusion criterion:
a.Intranasal, inhaled, topical steroids, or local steroid injections (e.g intra-articular injection)
b.Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
c.Steroids as premedication for hypersensitivity reactions (e.g CT scan premedication)
- Has a known history of active TB (Bacillus Tuberculosis)
- Previous additional malignancy that is processing or has required active treatment in the last 2years. Exceptions include:
o Non-melanomatous skin cancer (if adequately treated)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified