A Phase 2/3 interventional study of Letrozole Oral Product and Bicalutamide Oral Product in Recurrent Ovarian Cancer, Signal Transduction Pathway Deregulation and Therapy-Associated Cancer, sponsored by Gynaecologisch Oncologisch Centrum Zuid. Recruiting at 6 sites in Netherlands. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-04-18.
Sponsored by Gynaecologisch Oncologisch Centrum Zuid · Phase 2/3, Interventional, and Treatment
The purpose of this prospective, parallel-group, cohort study is to implement phenotype-guided targeted therapy based on functional signal transduction pathway (STP) activity in recurrent ovarian cancer patients using a novel mRNA-based assay. Existing targeted drugs with tolerable toxicity profiles are used to investigate the therapeutic value beyond their approved indication, which are deemed beneficial in the select group of patients with a relevant predominantly active functional STP, in order to improve survival and maintain quality of life.
Rationale: Ovarian cancer is one of the most lethal cancers in the world. Standard therapy consists of debulking surgery and chemotherapy. However, despite this aggressive treatment, recurrent disease almost invariably occurs resulting in a five-year survival rate of approximately 30%. Tumour growth is driven by several signal transduction pathways (STPs), and twelve major STPs have been identified as important for carcinogenesis. Currently, several targeted therapy drugs are available and new targeted drugs are being developed. With a newly developed technique, Signal Transduction Activation (STA) analysis, it is possible to assess which pathway is predominant in a specific (ovarian) cancer sample. Therefore, we hypothesize that specifically targeting the predominant STP might impair tumour growth and improve survival.
Objective: This study aims to investigate the progression-free survival (PFS) according to RECIST 1.1 criteria on matched targeted therapy by STA-analysis (PFS2) in comparison to the PFS recorded on the therapy administered immediately prior to enrolment (PFS1) in women with recurrent ovarian cancer.
Study design: A multi-centre prospective, parallel-group, cohort study. Study population: Recurrent ovarian cancer patients with platinum-resistant disease, patients who refrain from standard therapy and patients who are not yet eligible for standard palliative chemotherapy, including all histological subtypes.
Intervention: STA-analysis will be performed on a biopsy taken from the recurrent tumour. Patients will be included if a predominant pathway is identified for which a matched targeted drug is available and deemed adequate by the multidisciplinary tumour board. We will start with targeted therapy in patients with oestrogen receptor, androgen receptor, phosphoinositide 3-kinase and Hedgehog pathway active tumours, since targeted therapy interceding these pathways are easily available with tolerable side effects.
Main study parameters/endpoints: The primary outcome is therapy response defined as PFS2/PFS1 ratio according to RECIST 1.1 criteria. Secondary outcomes include the proportion of patients with an actionable active pathway and the proportion of patients receiving matched targeted therapy, best overall response (according to RECIST 1.1 criteria), one-year survival, overall survival, predictive value of STA-analysis results, side effects, quality of life, cost-effectiveness and change in STP activity score comparing the score before treatment and after disease progression.
3,381 studies on the registry are indexed under Ovarian Neoplasms; 790 are open to participants now.
This study's planned enrollment of 148 is above the median of 54 across 2,548 interventional studies indexed under Ovarian Neoplasms.
Browse Ovarian Neoplasms studies →Gynaecologisch Oncologisch Centrum Zuid is the lead sponsor of 6 studies on the registry; 3 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
In case of an aberrantly active Estrogen Receptor (ER) pathway, patients will be treated with Letrozole 2.5mg daily orally until progression of disease.
Drug: Letrozole Oral Product
In case of an aberrantly active androgen receptor (AR) pathway, patients will be treated with Bicalutamide 150mg daily orally until progression of disease.
Drug: Bicalutamide Oral Product
In case of an aberrantly active phosphoinositide 3-kinase (PI3K) pathway, patients will be treated with Everolimus 10mg daily orally until progression of disease.
Drug: Everolimus Oral Product
In case of an aberrantly active Hedgehog (HH) or PI3K pathway, patients will be treated with Itraconazole 300mg twice daily orally until progression of disease.
Drug: Itraconazole Oral Product
Letrozole 2.5mg tablet - 2.5mg once dailty until progression of disease.
Bicalutatmide 150mg tablet - 150mg once daily until progression of disease.
Everolimus 10mg tablet - 10mg once daily until progression of disease.
Itraconazole 100mg capsule - 300mg twice daily until progression of disease.
Progression free survival on matched targeted therapy determined by STP-activity (PFS2) in comparison to the PFS recorded on the therapy administered immediately prior to enrolment (PFS1).
PFS on matched targeted therapy (PFS2) is defined as the time from start of matched targeted therapy to disease progression, defined by RECIST 1.1 criteria, or death from any cause. PFS on prior therapy (PFS1) is defined as the time from start of the prior treatment to disease progression defined by RECIST 1.1 criteria
Time frame: From baseline until the date of documented disease progression or 12 months after the start of targeted therapy.
Proportion of patients with an actionable active pathway for which targeted therapy is recommended in relation to the number of patients who underwent a biopsy.
Time frame: From date of biopsy until the date of the result from Multi-disciplinary Tumor Board Meeting, up 14 days after biopsy date.
Proportion of patients who receive matched targeted therapy in relation to the number of patients included in each study arm.
Proportion of patients included in arm A, B, C, D.
Time frame: From start date matched targeted therapy until the end of the study enrollment, up to 36 months.
Best overall response defined by RECIST 1.1 criteria based on radiological imaging.
Time frame: From baseline, radiological evaluation every 12 weeks after the start of targeted therapy until the date of documented disease progression or death, whichever comes first, assessed up to 12 months.
One-year survival
One-year survival is defined as the time from start matched targeted therapy till death or the end of the one-year follow-up period.
Time frame: From start date of targeted therapy until date of death or one year follow-up, whichever comes first.
Overall survival
Defined as the time from start matched targeted therapy till death.
Time frame: From start date of targeted therapy until the date of death, assessed up to 36 months.
Predictive value of STA-analysis results on matched targeted therapy response.
Time frame: From start date targeted therapy until response evaluation at 12 weeks after start of targeted therapy.
Side effects
Assessed according to the PRO-CTCAE and NCI CTCAE 5.0
Time frame: From start date of targeted therapy after two weeks, every 12 weeks from targeted therapy start date, until 12 weeks after end of treatment.
Health Related Quality of Life
HRQoL is assessed using standardized questionnaires from the EORTC QLQ-C30 and QLQ-OV28.
Time frame: From baseline, every 12 weeks after start date of treatment until 12 weeks after end of treatment.
Cost-effectiveness
Standardized EuroQol 5D (EQ-5D-5L) questionnaire is used to calculated the cost-effectiveness.
Time frame: From baseline, every 12 weeks after start date of targeted therapy until 12 weeks after end of treatment.
Change in pathway activity score after disease progression compared to pathway activity score before start of matched therapy.
If pathway activity scores are available from a second (voluntary) biopsy for after treatment has ended and before standard (palliative) treatment has started, change in pathway scores are assessed.
Time frame: From date of biopsy until 4 weeks after date of documented progression of disease.
Plan to share: Undecided
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Studies of the drugs tested here: Letrozole · Bicalutamide · Everolimus · Itraconazole
Gynaecologisch Oncologisch Centrum Zuid