Back to results

Orteronel (TAK-700) in Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors. The Greko II Study. (Greko II)

Primary Purpose

Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors

Status

Terminated

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

Orteronel 300mg BID

About this trial

This is an interventional treatment trial for Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors focused on measuring Orteronel, Granulosa Cell Tumour

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Voluntary written informed consent.
Patients, even if surgically sterilized who:
1. Agree to practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, or
2. Agree to completely abstain from intercourse.
Patients 18 years or older.
Screening clinical laboratory values as specified below:
Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be <=2.5 X ULN.
Total bilirubin <=1.5 X ULN.
Estimated creatinine clearance using the Cockcroft-Gault formula must be >40 mL/minute.
Absolute neutrophil count (ANC) >=1500/mcL and platelet count >=100,000/mcL.
Histologically confirmed granulosa cell ovarian tumor with locally advanced non-resectable or metastatic disease, measurable or evaluable by RECIST.
Availability of sufficient biopsy material to confirm the malignant diagnosis of granulosa cell ovarian tumor by a centralized pathologist and to perform the determine the FOXL2 402C mutation → G (C134W). However study entry will be allowed based just on the histological local diagnosis.
Life expectancy >=12 weeks
Screening calculated ejection fraction of greater than or equal to normal by multiple gated acquisition (MUGA) scan, or by echocardiogram (ECHO).
Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before first dose of study drug/randomization.

Exclusion Criteria:

History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 (NCI CTCAE, version 4.02)(56), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
New York Heart Association Class III or IV heart failure.
ECG abnormalities of:
1. Q-wave infarction, unless identified 6 or more months prior to screening
2. QTc interval > 460 msec
Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum ?- human chorionic gonadotropin (?-hCG) pregnancy test result obtained during screening.
Patient has received other investigational drugs within 28 days before enrollment
Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy.
Prior therapy with orteronel, ketoconazole, abiraterone, aminoglutethimide or enzalutamide.
Patients received radical radiotherapy <= 4 weeks before starting the study treatment or who have not recovered from the toxicities of radiotherapy. Palliative radiotherapy of painful bone lesions is allowed up to 14 days before the start of study treatment.
Known hypersensitivity to compounds related to orteronel or to orteronel excipients.
Uncontrolled hypertension despite appropriate medical therapy (BP of greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the Screening visit). Note: patients may be rescreened after adjustment of antihypertensive medications.
Known active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator?s opinion, potentially interfere with participation in this study.
Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel.
Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of orteronel, including difficulty swallowing tablets.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Orteronel 300mg b.i.d.

Arm Description

Orteronel 300mg BID (600mg per day) will be administered to all included patients in a 28 days cycle schedule.

Outcomes

Primary Outcome Measures

Clinical benefit at 6 months

Clinical benefit is defined as the average of patients with radiological response (partial or complete) plus stable disease longer than 6 months by RECIST 1.1 criteria

Secondary Outcome Measures

Overall Response Rate

Overall Response Rate according to RECIST 1.1 criteria.

Progression free survival

Progression Free Survival defined as the time from the administration of the first dose of treatment to disease progression or death from any cause.

Overall Survival

Overall Survival defined as the time from first dose of treatment to patient death from any cause

Reduction of sex hormones production.

Significant reduction of sex hormones production will be considered as at least a reduction to half the basal level confirmed in one determination one month apart.

Toxicity profile

Frequency of each adverse event per patient

Full Information

NCT ID

NCT02101684

First Posted

March 26, 2014

Last Updated

March 2, 2018

Sponsor

Grupo Español de Tumores Huérfanos e Infrecuentes

Collaborators

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT02101684

Brief Title

Orteronel (TAK-700) in Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors. The Greko II Study.

Acronym

Greko II

Official Title

Open Label Phase II Clinical Trial of Orteronel (TAK-700) in Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors. The Greko II Study.

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Terminated

Why Stopped

Slow recruitment rate

Study Start Date

June 2014 (undefined)

Primary Completion Date

January 11, 2017 (Actual)

Study Completion Date

January 11, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Grupo Español de Tumores Huérfanos e Infrecuentes

Collaborators

Takeda

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Granulosa Cell ovarian carcinoma is an infrequent subtype of neoplasia well differentiated from epithelial tumors. They account for 5% of all ovarian malignancies and, with an incidence of 0.4-1.2 cases per 100000 habitants, is considered as a rare disease. Though most cases are identified at initial stages and can be cured through surgical resection, distant recurrences have been documented even 10 years after resecting the primary tumor. At advanced stage it is a lethal disease. Unfortunately because of the low incidence of this disease randomized clinical trials are lacking. In fact current evidence for treatment is provided by case reports, retrospective studies and phase II clinical trials performed one decade ago. Orteronel, a novel, orally active, selective inhibitor of 17,20-lyase, is being developed as an endocrine therapy for relevant hormone-sensitive cancers such as prostate cancer and breast cancer. Orteronel is expected to suppress sex hormone levels in both circulation and relevant hormone-dependent malignant tissue. Since sex hormone overproduction has been demonstrated in granulosa cell ovarian tumors and seems to play a major role in this disease, this study will assess the efficacy or orteronel treating such tumors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors

Keywords

Orteronel, Granulosa Cell Tumour

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Orteronel 300mg b.i.d.

Arm Type

Experimental

Arm Description

Orteronel 300mg BID (600mg per day) will be administered to all included patients in a 28 days cycle schedule.

Intervention Type

Drug

Intervention Name(s)

Orteronel 300mg BID

Primary Outcome Measure Information:

Title

Clinical benefit at 6 months

Description

Clinical benefit is defined as the average of patients with radiological response (partial or complete) plus stable disease longer than 6 months by RECIST 1.1 criteria

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Overall Response Rate

Description

Overall Response Rate according to RECIST 1.1 criteria.

Time Frame

Every 8 weeks, during 6 months

Title

Progression free survival

Description

Progression Free Survival defined as the time from the administration of the first dose of treatment to disease progression or death from any cause.

Time Frame

Every 8 weeks, during 6 months

Title

Overall Survival

Description

Overall Survival defined as the time from first dose of treatment to patient death from any cause

Time Frame

Every 12 weeks, untill death

Title

Reduction of sex hormones production.

Description

Significant reduction of sex hormones production will be considered as at least a reduction to half the basal level confirmed in one determination one month apart.

Time Frame

Every 8 weeks, during 6 months

Title

Toxicity profile

Description

Frequency of each adverse event per patient

Time Frame

Every 4 weeks, untill end of treatment (6 months estimated)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Voluntary written informed consent. Patients, even if surgically sterilized who: Agree to practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, or Agree to completely abstain from intercourse. Patients 18 years or older. Screening clinical laboratory values as specified below: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be <=2.5 X ULN. Total bilirubin <=1.5 X ULN. Estimated creatinine clearance using the Cockcroft-Gault formula must be >40 mL/minute. Absolute neutrophil count (ANC) >=1500/mcL and platelet count >=100,000/mcL. Histologically confirmed granulosa cell ovarian tumor with locally advanced non-resectable or metastatic disease, measurable or evaluable by RECIST. Availability of sufficient biopsy material to confirm the malignant diagnosis of granulosa cell ovarian tumor by a centralized pathologist and to perform the determine the FOXL2 402C mutation → G (C134W). However study entry will be allowed based just on the histological local diagnosis. Life expectancy >=12 weeks Screening calculated ejection fraction of greater than or equal to normal by multiple gated acquisition (MUGA) scan, or by echocardiogram (ECHO). Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before first dose of study drug/randomization. Exclusion Criteria: History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 (NCI CTCAE, version 4.02)(56), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. New York Heart Association Class III or IV heart failure. ECG abnormalities of: Q-wave infarction, unless identified 6 or more months prior to screening QTc interval > 460 msec Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum ?- human chorionic gonadotropin (?-hCG) pregnancy test result obtained during screening. Patient has received other investigational drugs within 28 days before enrollment Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy. Prior therapy with orteronel, ketoconazole, abiraterone, aminoglutethimide or enzalutamide. Patients received radical radiotherapy <= 4 weeks before starting the study treatment or who have not recovered from the toxicities of radiotherapy. Palliative radiotherapy of painful bone lesions is allowed up to 14 days before the start of study treatment. Known hypersensitivity to compounds related to orteronel or to orteronel excipients. Uncontrolled hypertension despite appropriate medical therapy (BP of greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the Screening visit). Note: patients may be rescreened after adjustment of antihypertensive medications. Known active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator?s opinion, potentially interfere with participation in this study. Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel. Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of orteronel, including difficulty swallowing tablets.

Overall Study Officials: