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Phase I/II, Multicenter, Open-label, Clinical and Pharmacokinetic Study of Lurbinectedin in Combination with Irinotecan in Pretreated Patients with Selected Advanced Solid Tumors.
EU CTIS ID: 2024-515394-10-00
What this study is testing
Phase I escalation stage: To determine the maximum tolerated dose (MTD) and the RD of lurbinectedin in combination with irinotecan in patients with selected advanced solid tumors. Phase II expansion stage: To obtain information on the clinical antitumor activity of this combination in patients with selected advanced solid tumors.
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Voluntarily signed and dated written informed consent prior to any specific-study procedure
- Phase II expansion stage: Tumor-specific cohort(s) at the RD: a)Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. For patients with glioblastoma: Measurable disease according to RECISTv.1.1 and Response Assessment in Neuro- Oncology (RANO) criteria b)Documented disease progression per RECISTv.1.1 during or immediately after last therapy according to any of the aforementioned criteria. For patients with glioblastoma: Documented disease progression per RECISTv.1.1 and RANO criteria
- At least 3 weeks since the last anticancer therapy, (including immunotherapy, investigational drugs and radiotherapy), and at least 6 weeks since nitrosoureas and mitomycin C (systemic). For biological/investigational anticancer therapies given orally, the aforementioned period of at least 3 weeks could be changed for one of at least 5 half-lives (whichever occurred first), provided that the therapy is given as single agent and not combined with other drugs. If this is not the case, this exception will not be acceptable. For patients with glioblastoma: at least 12 weeks since the end of radiotherapy, except if: a)The patient has a new lesion outside of the radiotherapy field, or b)The patient has undergone brain surgery to remove the tumor before study entry, and progressive disease has been confirmed histologically. Note: washout periods will be referred to the day of first cycle administration (Day1), not to the day of registration (Day0)
- Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤7 days before inclusion in the trial): a) Platelet count ≥100×10^9/L, hemoglobin ≥9.0g/dL and absolute neutrophil count (ANC) ≥2.0×10^9/L b)AST and ALT ≤3.0×ULN, even in the presence of liver metastases c)Alkaline phosphatase (ALP) ≤2.5×ULN (≤5 × ULN if disease-related/in the case of liver metastases) d)Total bilirubin ≤1.5×ULN or direct bilirubin ≤ULN e)INR <1.5 (except if patient is on oral anticoagulation therapy) f)Calculated creatinine clearance (CrCL) ≥30 mL/minute (using Cockcroft-Gault formula) g)Creatine phosphokinase (CPK) ≤2.5×ULN h)Albumin ≥3.0 g/dL* *Albumin transfusion to increase the blood level in order to fulfill the inclusion criterion is strictly forbidden
- Recovery to grade ≤1 or to baseline from any AE derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or peripheral neuropathy and/or fatigue grade ≤2).
- Age ≥18years
You likely can't join if
- Concomitant diseases/conditions: a)History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within the previous year b)Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment c) Myopathy or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 × ULN in two different determinations performed one week apart) d) Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C. Known Gilbert disease e) Active uncontrolled infection f) Known human immunodeficiency virus (HIV) or known hepatitis C virus (HCV) infection or active hepatitis B g) Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion or paralysis h) Evident symptomatic pulmonary fibrosis or interstitialpneumonitis, pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days i) Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study j) Active COVID-19 disease k) Hypersensitivity to any of the study drugs or their excipients.
- Prior treatment with lurbinectedin, trabectedin (Yondelis®) or topoisomerase I inhibitors (irinotecan, topotecan, etc.). Prior topoisomerase inhibitors (e.g., irinotecan) are only allowed in patients with colorectal carcinoma or NENs
- Prior bone marrow or stem cell transplantation, or radiation therapy in more than 35% of bone marrow
- Known brain metastases or leptomeningeal disease involvement. Glioblastoma lesions (primary or locally advanced) are eligible. Exception: patients with brain metastases are eligible provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment (patients taking steroids in the process of already being tapered within two weeks prior to screening are allowed). Brain CT-scan or MRI results must be provided at baseline.
- Women who are pregnant or breast feeding and fertile patients (men and women) who are not using an effective method of contraception * * Women of childbearing potential (WOCBP) must agree to use an effective contraception method to avoid pregnancy during the course of the trial (and for at least six months after the last infusion). Fertile male patients must agree to refrain from fathering a child or donating sperm during the trial and for four months after the last infusion
- Limitation of the patient's ability to comply with the treatment or follow-up protocol
See the full eligibility criteria
Who can join
- Voluntarily signed and dated written informed consent prior to any specific-study procedure
- Phase II expansion stage: Tumor-specific cohort(s) at the RD: a)Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. For patients with glioblastoma: Measurable disease according to RECISTv.1.1 and Response Assessment in Neuro- Oncology (RANO) criteria b)Documented disease progression per RECISTv.1.1 during or immediately after last therapy according to any of the aforementioned criteria. For patients with glioblastoma: Documented disease progression per RECISTv.1.1 and RANO criteria
- At least 3 weeks since the last anticancer therapy, (including immunotherapy, investigational drugs and radiotherapy), and at least 6 weeks since nitrosoureas and mitomycin C (systemic). For biological/investigational anticancer therapies given orally, the aforementioned period of at least 3 weeks could be changed for one of at least 5 half-lives (whichever occurred first), provided that the therapy is given as single agent and not combined with other drugs. If this is not the case, this exception will not be acceptable. For patients with glioblastoma: at least 12 weeks since the end of radiotherapy, except if: a)The patient has a new lesion outside of the radiotherapy field, or b)The patient has undergone brain surgery to remove the tumor before study entry, and progressive disease has been confirmed histologically. Note: washout periods will be referred to the day of first cycle administration (Day1), not to the day of registration (Day0)
- Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤7 days before inclusion in the trial): a) Platelet count ≥100×10^9/L, hemoglobin ≥9.0g/dL and absolute neutrophil count (ANC) ≥2.0×10^9/L b)AST and ALT ≤3.0×ULN, even in the presence of liver metastases c)Alkaline phosphatase (ALP) ≤2.5×ULN (≤5 × ULN if disease-related/in the case of liver metastases) d)Total bilirubin ≤1.5×ULN or direct bilirubin ≤ULN e)INR <1.5 (except if patient is on oral anticoagulation therapy) f)Calculated creatinine clearance (CrCL) ≥30 mL/minute (using Cockcroft-Gault formula) g)Creatine phosphokinase (CPK) ≤2.5×ULN h)Albumin ≥3.0 g/dL* *Albumin transfusion to increase the blood level in order to fulfill the inclusion criterion is strictly forbidden
- Recovery to grade ≤1 or to baseline from any AE derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or peripheral neuropathy and/or fatigue grade ≤2).
- Age ≥18years
- ECOG performance status ≤1.
- Life expectancy ≥3 months.
- Histologically or cytologically confirmed diagnosis of advanced disease of any of the following tumor types: - Lurbinectedin Escalation Group and Irinotecan Escalation Group: a)Glioblastoma b)Soft-tissue sarcoma (excluding GIST) c)Endometrial carcinoma d)Epithelial ovarian carcinoma (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas) regardless of platinum sensitivity e)Mesothelioma f)GEP-NET g)SCLC h)Pancreatic adenocarcinoma i)Gastric carcinoma j)CRC
- Histologically or cytologically confirmed diagnosis of advanced disease of any of the following tumor types: - Intermediate Escalation Group: a)Endometrial carcinoma b)SCLC c)Other solid tumors may be included, if appropriate, after discussion between the Investigators and the Sponsor
- Histologically or cytologically confirmed diagnosis of advanced disease of any of the following tumor types: For the Phase II expansion stage: a)Glioblastoma b)Soft tissue sarcoma (including synovial sarcoma) c)Endometrial carcinoma d)SCLC e)Neuroendocrine tumors - Group 1: Poorly differentiated grade 3 NEC (Ki-67 >20%) according to the 2019 WHO classification of tumors of the digestive system, of gastroenteropancreatic origin or unknown primary site (lung primary tumors will be excluded) - Group 2: Well differentiated grade 2 (Ki-67 3-20%) or grade 3 (Ki-67 21-55%) GEP-NETs according to the 2019 WHO classification of tumors of the digestive system
- The number of prior lines of therapy allowed per patient will be as follows: -Phase I Escalation Stage: No more than 2 prior lines of cytotoxiccontaining chemotherapy regimens for advanced disease
- The number of prior lines of therapy allowed per patient will be as follows: -Phase II Lurbinectedin Expansion Stage: •For SCLC, 1 prior line of platinum-containing chemotherapy with/without antibodies against PD-1 or PD-L1 •For NENs, in Group 1 (patients with poorly differentiated NEC of gastroenteropancreatic origin or unknown primary site, excluding lung primary tumors), one prior line of platinum-based chemotherapy; and in Group 2 (patients with well differentiated GEP-NETs), no more than 3 prior lines of systemic therapy (that may include somatostatin analogues, chemotherapy, everolimus and/or sunitinib) •For all other tumor types, no more than 2 prior lines of cytotoxiccontaining chemotherapy regimens for advanced disease There is no limit for prior targeted therapy, hormonal therapy and immunotherapy (such as nivolumab)
What rules you out
- Concomitant diseases/conditions: a)History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within the previous year b)Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment c) Myopathy or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 × ULN in two different determinations performed one week apart) d) Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C. Known Gilbert disease e) Active uncontrolled infection f) Known human immunodeficiency virus (HIV) or known hepatitis C virus (HCV) infection or active hepatitis B g) Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion or paralysis h) Evident symptomatic pulmonary fibrosis or interstitialpneumonitis, pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days i) Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study j) Active COVID-19 disease k) Hypersensitivity to any of the study drugs or their excipients.
- Prior treatment with lurbinectedin, trabectedin (Yondelis®) or topoisomerase I inhibitors (irinotecan, topotecan, etc.). Prior topoisomerase inhibitors (e.g., irinotecan) are only allowed in patients with colorectal carcinoma or NENs
- Prior bone marrow or stem cell transplantation, or radiation therapy in more than 35% of bone marrow
- Known brain metastases or leptomeningeal disease involvement. Glioblastoma lesions (primary or locally advanced) are eligible. Exception: patients with brain metastases are eligible provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment (patients taking steroids in the process of already being tapered within two weeks prior to screening are allowed). Brain CT-scan or MRI results must be provided at baseline.
- Women who are pregnant or breast feeding and fertile patients (men and women) who are not using an effective method of contraception * * Women of childbearing potential (WOCBP) must agree to use an effective contraception method to avoid pregnancy during the course of the trial (and for at least six months after the last infusion). Fertile male patients must agree to refrain from fathering a child or donating sperm during the trial and for four months after the last infusion
- Limitation of the patient's ability to comply with the treatment or follow-up protocol
The study team makes the final eligibility decision.
Where it's taking place
- United States
- Switzerland
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; Switzerland. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.