Sotorasib Combined With First-line Chemotherapy for Advanced Pancreatic Adenocarcinoma (PANSOTO)
Sotorasib Combined With First-line Chemotherapy for Advanced Pancreatic Adenocarcinoma With KRAS p.G12C Mutation
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Grupo de Tratamiento de los Tumores Digestivos
- Phone Number: +034 913 788 275
- Email: secretariattd@ttdgroup.org
Study Locations
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France
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Avignon, France, France
- Not yet recruiting
- Sainte Catherine - Institut Avignon Provence
-
Principal Investigator:
- Clémence TOULLEC, MD
-
Besançon, France, France
- Not yet recruiting
- CHU Besançon - Hôpital Jean Minjoz
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Principal Investigator:
- Angélique Vienot, MD
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Brest, France, France
- Not yet recruiting
- CHU Brest - Hôpital Morvan
-
Principal Investigator:
- Jean Philippe Metges, MD
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Lille, France, France
- Not yet recruiting
- Chu de Lille - Claude Huriez
-
Principal Investigator:
- Pauline Parent, MD
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Lyon, France, France
- Not yet recruiting
- Hôpital Léon Berard
-
Principal Investigator:
- Philippe Cassier, MD
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Pessac, France, France
- Not yet recruiting
- CHU Bordeaux - Hôpital Haut Lévèque
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Principal Investigator:
- Jean Frederic Blanc, MD
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Poitiers, France, France
- Not yet recruiting
- CHU Poitiers
-
Principal Investigator:
- David TOUGERON, MD
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Reims, France, France
- Not yet recruiting
- CHU Reims - Hôpital Robert Debré
-
Principal Investigator:
- Olivier BOUCHE, MD
-
Toulouse, France, France
- Not yet recruiting
- CHU Toulouse
-
Principal Investigator:
- Nadim FARES, MD
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Villejuif, France, France
- Not yet recruiting
- Hôpital Paul-Brousse
-
Principal Investigator:
- Pascal Hammel, MD
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-
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Aragon
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Zaragoza, Aragon, Spain
- Recruiting
- Hospital Universitario Miguel Servet
-
Principal Investigator:
- Roberto Pazo, MD
-
-
Barcelona
-
Barcelona, Barcelona, Spain
- Recruiting
- Hospital Clinic
-
Contact:
- Florian Castet, MD
-
Principal Investigator:
- Florian Castet, MD
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Barcelona, Barcelona, Spain
- Recruiting
- Hospital Universitari Vall d'Hebron
-
Principal Investigator:
- Jaume Capdevila, MD
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Barcelona, Barcelona, Spain
- Recruiting
- Institut Català D'Oncologia L'Hospitalet (Ico)
-
Principal Investigator:
- Berta Laquente Saez, MD
-
-
Cantabria
-
Santander, Cantabria, Spain
- Recruiting
- Hospital Universitario Marqués de Valdecilla
-
Principal Investigator:
- Eva Martínez de Castro, MD
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Córdoba
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Córdoba, Córdoba, Spain
- Recruiting
- Hospital Reina Sofía
-
Principal Investigator:
- Maria Teresa Cano Osuna, MD
-
-
Guipúzcoa
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Donostia / San Sebastian, Guipúzcoa, Spain
- Recruiting
- Hospital Universitario Donostia-Donostia Unibertsitate Ospitalea
-
Principal Investigator:
- Beatriz Sánchez Casi, MD
-
-
Madrid
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Madrid, Madrid, Spain
- Recruiting
- Hospital General Universitario Gregorio Marañón
-
Principal Investigator:
- Andrés Muñoz, MD
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Madrid, Madrid, Spain
- Recruiting
- Hospital Universitario 12 de Octubre
-
Principal Investigator:
- Rocío García Carbonero, MD
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Madrid, Madrid, Spain
- Recruiting
- Hospital Clinico San Carlos
-
Principal Investigator:
- Beatriz García Paredes, MD
-
-
Málaga
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Málaga, Málaga, Spain
- Recruiting
- Complejo Hospitalario Regional de Málaga
-
Principal Investigator:
- Inmaculada Ales, MD
-
-
Navarre
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Pamplona, Navarre, Spain
- Recruiting
- Complejo Hospitalario de Navarra
-
Principal Investigator:
- Ruth Vera, MD
-
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OURENSE
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Ourense, OURENSE, Spain
- Recruiting
- Complexo Hospitalario Universitario de Ourense
-
Principal Investigator:
- Ana Fernández Montes, MD
-
-
Principality of Asturias
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Oviedo, Principality of Asturias, Spain
- Recruiting
- Hospital Universitario Central de Asturias
-
Principal Investigator:
- Paula Jiménez Fonseca, MD
-
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SALAMANCA
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Salamanca, SALAMANCA, Spain
- Recruiting
- Hospital Universitario De Salamanca
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Principal Investigator:
- Luis Miguel Navarro Martín, MD
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Valencia
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Valencia, Valencia, Spain
- Recruiting
- Hospital General Universitario de Valencia
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Principal Investigator:
- Miriam Lobo de Mena, MD
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
1) Willing and able to provide informed consent. 2) Men or women aged ≥ 18 years old. 3) Using effective contraceptive measures or sexual abstinence during the treatment, up to 7 days after the last dose of sotorasib, for at least 6 months after the last dose of gem/nab-P and for 15 months after the last dose of mFOLFIRINOX for woman of childbearing age and 12 months after stopping mFOLFIRINOX for men:
- Female of childbearing potential using a highly effective method of contraception (i.e., a method with less than 1% failure rate [e.g., sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner])
- Male agreeing to use condoms or having a partner who is using a highly efficient method of contraception as described above 4) Pathologically confirmed treatment-naïve of locally advanced or metastatic pancreatic adenocarcinoma harboring KRAS p.G12C mutation assessed by means of a IVDR compliant test) 5) Measurable disease per RECIST 1.1 criteria. 6) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 7) Life expectancy > 3 months, in the opinion of the investigator. 8) Adequate hematologic, renal and hepatic organ function, defined as the following within 10 days prior study inclusion:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility)
- Hemoglobin ≥ 9.0 g/dL (without transfusion within 2 weeks of laboratory test used to determine eligibility)
- Platelet count ≥ 100 x 109/L (without transfusion within 2 weeks of laboratory test used to determine eligibility)
- Aspartate aminotransferase (AST) and ALT ≤ 2.5 times the upper limit of normal (ULN) or ≤5 times if liver metastasis
- Serum bilirubin ≤ 1.5 x ULN
- International normalized ratio (INR) ≤ 1.5 x ULN. Prothrombin time (PT) ≤ 1.5 x ULN may be used instead of INR for sites whose laboratory do not report INR
- Creatinine clearance ≥ 30 mL/min (estimated by Cockcroft-Gault equation) 9) Ability to take oral medications and willing to record daily adherence to investigational product.
Exclusion Criteria:
- Patients with resectable or borderline resectable pancreatic cancer.
- Known history or positive viral test for human immunodeficiency virus (HIV).
- Peripheral sensory neuropathy. 4 )Proven complete dihydropyrimidine dehydrogenase (DPD) deficiency for patients that will be treated with mFOLFIRINOX.
5) Poor nutritional status (albumin <3 g/L or weight loss >10% during the last 4 weeks).
6) Patients with known active hepatitis (i.e., Hepatitis B or C)
- Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA 7) Female: currently pregnant or breast-feeding or who plan to breastfeed while on study though 7 additional days after the last dose of sotorasib and for at least 6 months afterwards after the last dose of gem/nab-P or 15 months after the last dose of mFOLFIRINOX.
8) Myocardial infarction within 6 months of study Day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or cardiac arrhythmia requiring medication 9) Prior anti-tumor treatment for metastatic or locally advanced pancreatic adenocarcinoma*. Prior chemotherapy or radiotherapy in the adjuvant or neoadjuvant setting is acceptable if received > 6 months prior to study enrolment
*If initiation of treatment is deemed urgent by the investigator, patients can receive 1st month of Standard of Care (SoC) gem/nab-P (1 cycle) or FOLFIRINOX (2 cycles) during screening. This first month of gem/nab-P or FOLFIRINOX is not a requirement of the study and is not part of this clinical study 10) Active infection requiring antibiotics within 1 weeks of study enrollment. 11) Other malignancy unless curatively treated with no evidence of disease for ≥2 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, and/or ductal carcinoma in situ.
12) Significant gastrointestinal disorder that results in significant malabsorption, requirement for IV alimentation, or inability to take oral medication.
13) History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis.
14) Presence of any condition that, in the opinion of the investigator, renders the patient at high risk from treatment complications or might affect the interpretation of the results of the study.
15) Significant uncontrolled concomitant disease that could affect compliance with protocol procedures or interpretation of results or that pose a risk to patient safety, in the opinion of the investigator.
16) Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly. Patients with PleurX catheters or intraperitoneal drainage catheters in place may be considered for the study with Medical Monitor approval.
17) Major surgery within 4 weeks of study Day 1 18) Prior/concomitant therapy:
- Previous treatment with a KRASG12C inhibitor
- Use of warfarin. Other anticoagulation may be allowed
- Use of known cytochrome P450 (CYP) 3A4 sensitive substrates and P-glycoprotein (P-gp) substrates (with a narrow therapeutic window), within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer, prior to study Day 1 (see examples of sensitive substrates and P-glycoprotein substrates in Appendix A) except for those investigational treatments administered as part of the study scheme that will be subject to specific PK analysis.
- Use of strong inducers of CYP3A4 (including herbal supplements such as St John's wort) within 14 days or 5 half-lives (whichever is longer) prior to study Day 1 (see examples of strong inducers of CYP3A4 in Appendix A)
- Live attenuated vaccines (against yellow fever, chickenpox, shingles, measles, mumps, rubella, tuberculosis, rotavirus and influenza), within 30 days prior of the first dose of study treatment.
Brivudine-based treatments within 4 weeks before treatment with 5-fluorouracil. 19) Patient has known sensitivity to any of the products or components to be administered during the study.
20) History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: First-line chemotherapy (gem/nab-P or FOLFIRINOX) combined with sotorasib
A minimum of 6 and a maximum of 15 patients will be enrolled to receive first-line chemotherapy (gem/nab-P or mFOLFIRINOX at investigator choice) in combination with sotorasib 960 mg daily (QD).mFOLFIRINOX is recommended for patients with ECOG PS of 0 to 1, favourable comorbidity profile, patient preference and a support system for aggressive medical therapy, and access to chemotherapy port and infusion pump management services.
Gem/nab-P is recommended for patients with ECOG PS of 0 to 1, a relatively favourable comorbidity profile, and patient preference and a support system for relatively aggressive medical therapy.
Gem/nab-P is therefore the preferred first line treatment for patients expected to be intolerant to mFOLFIRINOX.
|
A minimum of 6 and a maximum of 15 patients will be enrolled to receive first-line chemotherapy (gem/nab-P or mFOLFIRINOX at investigator choice) in combination with sotorasib 960 mg daily (QD).
The treatment with gem/nab-P and mFOLFIRINOX should be managed as per clinical practice.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
To evaluate the safety and tolerability of sotorasib combined with first-line chemotherapy for locally advanced or metastatic pancreatic adenocarcinoma harboring KRAS p.G12C mutation.
Time Frame: 60 months
|
Incidence of treatment-emergent adverse events (TEAEs) and related TEAEs (TRAEs) according to CTCAE V5.0.
|
60 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
To evaluate the progression-free survival assessed by CT or MRI using RECIST 1.1 criteria of first-line chemotherapy combined with sotorasib for advanced pancreatic adenocarcinoma harboring KRAS p.G12C mutation
Time Frame: 60 months
|
Progression-Free Survival (PFS) is defined as time from the first day of the study treatment (Day 1) until disease progression or death from any cause, whichever occurs first, for all patients, according to the investigator criteria.
|
60 months
|
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To evaluate the overall survival of first-line chemotherapy combined with sotorasib for advanced pancreatic adenocarcinoma harboring KRAS p.G12C mutation.
Time Frame: 60 months
|
The overall survival (OS) is defined as time from Day 1 until death from any cause.
|
60 months
|
|
Overall response (OR)
Time Frame: 60 months
|
The overall response (OR) is defined as the best overall response complete response (CR) or partial response (PR), assessed per RECIST 1.1.
|
60 months
|
|
Disease control (DC)
Time Frame: 60 months
|
The disease control (DC) is defined as the best overall response of CR or PR or of stable disease.
|
60 months
|
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Duration of response (DOR)
Time Frame: 60 months
|
The duration of response (DOR) is defined as the time from onset of response to progression or death due to any reason, whichever occurs earlier.
|
60 months
|
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Duration of stable disease
Time Frame: 60 months
|
The duration of stable disease is defined as the time from first disease control to disease progression per RECIST 1.1 criteria or death (due to any cause).
For patients with disease control who have not progressed or died at last observation, duration of disease control will be censored at their last evaluable disease assessment date.
|
60 months
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- TTD-24-01
- 2024-516233-12-00 (Ctis)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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