Informations générales (source: ClinicalTrials.gov)
A Randomized Phase 2 Study of Ompenaclid Versus Placebo in Combination With FOLFIRI Plus Bevacizumab in Patients With Previously Treated RAS Mutant Advanced or Metastatic Colorectal Cancer
Interventional
Phase 2
Inspirna, Inc. (Voir sur ClinicalTrials)
octobre 2023
août 2028
02 octobre 2024
The purpose of this study is to measure tumor response to treatment with ompenaclid
(RGX-202) in patients with previously treated RAS mutant advanced or metastatic CRC. All
patients will receive treatment with FOLFIRI and bevacizumab. In addition, patients will
be randomized to receive either ompenaclid 3000 mg BID or matching placebo (herein
referred to as Study Drug). Each treatment cycle is 28 days in duration.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Michel DUCREUX | 28/06/2024 12:47:53 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| GH PARIS SITE SAINT JOSEPH | Eric Raymond | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Georges-François Leclerc - 21000 - Dijon - France | François Ghiringhelli, MD | Contact (sur clinicalTrials) | |||
| CHU Hôpital Jean Minjoz - 25000 - Besançon - France | Christophe Borg | Contact (sur clinicalTrials) | |||
| CHU Nantes -hopital hotel Dieu - 44093 - Nantes - Loire-Atlantique - France | Dahna Coupez | Contact (sur clinicalTrials) | |||
| Hopital Prive des Cotes d'Armor - 22190 - Plérin - France | Jérôme Martin-Babau | Contact (sur clinicalTrials) | |||
| Institut de Cancerologie de l'Ouest - 44805 - Saint Herblain Cedex - France | Judith Raimbourg | Contact (sur clinicalTrials) | |||
| Institut Paoli-Calmettes - 13009 - Marseille - France | christelle De la Fouchardiere, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria
1. Advanced disease, defined as cancer that is either metastatic or locally advanced
and unresectable and for which additional radiation therapy or other locoregional
therapies are not considered feasible.
2. Progression of disease after receiving only 1 prior regimen considered standard of
care for CRC in the advanced/metastatic setting, and it must have been an
oxaliplatin containing regimen. Patients who have mismatch repair deficiency/ high
microsatellite instability (dMMR/MSI-H) CRC must have also received prior treatment
with pembrolizumab or a Food and Drug Administration (FDA)/European Union
(EU)-approved programmed cell death protein 1 (PD-1)/ programmed death-ligand 1
(PD-L1) inhibitor. Patients may have received prior treatment with bevacizumab or an
European Medicines Agency (EMA) approved biosimilar. Patients who developed
metastatic CRC within 12 months of completion of adjuvant oxaliplatin and 5-FU based
therapy are also eligible.
3. Histologic or cytologic evidence of a malignant colorectal tumor of adenocarcinoma
or poorly differentiated histology that is laboratory-confirmed to be RAS mutant.
Confirmation of RAS mutant status by liquid biopsy is acceptable only if the tumor
sample is not available and the liquid biopsy was performed before initiation of the
patient's prior treatment regimen. Patients who convert to RAS mutant status after
initially having documented wild-type histology are not eligible.
4. Disease that is measurable by standard imaging techniques by Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1. For patients with prior radiation
therapy, measurable lesions must be outside of any prior radiation field(s), unless
disease progression has been documented at that disease site subsequent to
radiation.
5. At least 18 years old.
6. ECOG performance score ≤ 1.
7. Adequate baseline organ function, as demonstrated by the following:
1. Calculated creatinine clearance > 60 mL/min per institutional standard.
2. Serum albumin ≥ 2.5 g/dL.
3. Bilirubin ≤ 1.5 x institutional upper limit of normal range (ULN).
4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x
institutional ULN; patients with hepatic metastases may have AST and ALT ≤ 5 x
institutional ULN.
5. Absolute neutrophil count (ANC) ≥1.5x109/L.
6. Hemoglobin ≥ 8 g/dL and no red blood cell (RBC) transfusions during the prior
14 days.
7. Platelet count ≥ 100 x 109/L and no platelet transfusions during the prior 14
days.
8. If not taking warfarin (or similar vitamin K inhibitor) the following values are
required: international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5
x ULN and either partial thromboplastin time or activated partial thromboplastin
time (PTT or aPTT) ≤ 1.5 x ULN. Patients on warfarin (or similar vitamin K
inhibitor) may be included if on a stable dose with a therapeutic INR < 3.5.
9. Left ventricular ejection fraction (LVEF) x 45% as determined by either
echocardiography (ECHO) or multigated acquisition (MUGA) scanning.
10. Woman of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test within 2 weeks prior to treatment.
11. Men and WOCBP must agree to use acceptable contraceptive methods for the duration of
time on the study and continue to use acceptable contraceptive methods for at least
6 months from the last dose of bevacizumab or 2 months after the last dose of
ompenaclid, whichever is longer.
12. Provides signed informed consent prior to initiation of any study-specific
procedures or treatment.
13. Able to adhere to the study visit schedule and other protocol requirements,
including follow-up for survival assessment
Exclusion Criteria:
1. Persistent clinically significant toxicities (Grade ≥ 2) from previous anticancer
therapy. Excluded are Grade 2 chemotherapy-related neuropathy and alopecia which are
permitted and Grade 2 laboratory abnormalities if they are not associated with
symptoms, are not considered clinically significant by the Investigator, or can be
managed with available medical therapies.
2. CRC with histology (or component of histology) consistent with small cell,
neuroendocrine, or squamous carcinoma, or lymphoma.
3. Received treatment with chemotherapy, external-beam radiation, or other systemic
anticancer therapy within 14 days prior to study therapy administration (42 days for
prior nitrosourea or mitomycin-C).
4. Received treatment with an investigational systemic anticancer agent within 5 half
lives of the investigational systemic therapy or within 28 days, whichever is
shorter prior to Study Drug administration.
5. Has an additional active malignancy that may confound the assessment of the study
endpoints. Patients with a past cancer history with substantial potential for
recurrence must be discussed with the Medical Monitor before study entry. Patients
with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin
cancer, carcinoma in situ (including transitional cell carcinoma, cervical
intraepithelial neoplasia, and melanoma in situ), organ-confined prostate cancer
with no evidence of progressive disease.
1. Advanced disease, defined as cancer that is either metastatic or locally advanced
and unresectable and for which additional radiation therapy or other locoregional
therapies are not considered feasible.
2. Progression of disease after receiving only 1 prior regimen considered standard of
care for CRC in the advanced/metastatic setting, and it must have been an
oxaliplatin containing regimen. Patients who have mismatch repair deficiency/ high
microsatellite instability (dMMR/MSI-H) CRC must have also received prior treatment
with pembrolizumab or a Food and Drug Administration (FDA)/European Union
(EU)-approved programmed cell death protein 1 (PD-1)/ programmed death-ligand 1
(PD-L1) inhibitor. Patients may have received prior treatment with bevacizumab or an
European Medicines Agency (EMA) approved biosimilar. Patients who developed
metastatic CRC within 12 months of completion of adjuvant oxaliplatin and 5-FU based
therapy are also eligible.
3. Histologic or cytologic evidence of a malignant colorectal tumor of adenocarcinoma
or poorly differentiated histology that is laboratory-confirmed to be RAS mutant.
Confirmation of RAS mutant status by liquid biopsy is acceptable only if the tumor
sample is not available and the liquid biopsy was performed before initiation of the
patient's prior treatment regimen. Patients who convert to RAS mutant status after
initially having documented wild-type histology are not eligible.
4. Disease that is measurable by standard imaging techniques by Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1. For patients with prior radiation
therapy, measurable lesions must be outside of any prior radiation field(s), unless
disease progression has been documented at that disease site subsequent to
radiation.
5. At least 18 years old.
6. ECOG performance score ≤ 1.
7. Adequate baseline organ function, as demonstrated by the following:
1. Calculated creatinine clearance > 60 mL/min per institutional standard.
2. Serum albumin ≥ 2.5 g/dL.
3. Bilirubin ≤ 1.5 x institutional upper limit of normal range (ULN).
4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x
institutional ULN; patients with hepatic metastases may have AST and ALT ≤ 5 x
institutional ULN.
5. Absolute neutrophil count (ANC) ≥1.5x109/L.
6. Hemoglobin ≥ 8 g/dL and no red blood cell (RBC) transfusions during the prior
14 days.
7. Platelet count ≥ 100 x 109/L and no platelet transfusions during the prior 14
days.
8. If not taking warfarin (or similar vitamin K inhibitor) the following values are
required: international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5
x ULN and either partial thromboplastin time or activated partial thromboplastin
time (PTT or aPTT) ≤ 1.5 x ULN. Patients on warfarin (or similar vitamin K
inhibitor) may be included if on a stable dose with a therapeutic INR < 3.5.
9. Left ventricular ejection fraction (LVEF) x 45% as determined by either
echocardiography (ECHO) or multigated acquisition (MUGA) scanning.
10. Woman of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test within 2 weeks prior to treatment.
11. Men and WOCBP must agree to use acceptable contraceptive methods for the duration of
time on the study and continue to use acceptable contraceptive methods for at least
6 months from the last dose of bevacizumab or 2 months after the last dose of
ompenaclid, whichever is longer.
12. Provides signed informed consent prior to initiation of any study-specific
procedures or treatment.
13. Able to adhere to the study visit schedule and other protocol requirements,
including follow-up for survival assessment
Exclusion Criteria:
1. Persistent clinically significant toxicities (Grade ≥ 2) from previous anticancer
therapy. Excluded are Grade 2 chemotherapy-related neuropathy and alopecia which are
permitted and Grade 2 laboratory abnormalities if they are not associated with
symptoms, are not considered clinically significant by the Investigator, or can be
managed with available medical therapies.
2. CRC with histology (or component of histology) consistent with small cell,
neuroendocrine, or squamous carcinoma, or lymphoma.
3. Received treatment with chemotherapy, external-beam radiation, or other systemic
anticancer therapy within 14 days prior to study therapy administration (42 days for
prior nitrosourea or mitomycin-C).
4. Received treatment with an investigational systemic anticancer agent within 5 half
lives of the investigational systemic therapy or within 28 days, whichever is
shorter prior to Study Drug administration.
5. Has an additional active malignancy that may confound the assessment of the study
endpoints. Patients with a past cancer history with substantial potential for
recurrence must be discussed with the Medical Monitor before study entry. Patients
with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin
cancer, carcinoma in situ (including transitional cell carcinoma, cervical
intraepithelial neoplasia, and melanoma in situ), organ-confined prostate cancer
with no evidence of progressive disease.