Colorectal Cancer Clinical Trial
— KontRASt-03Official title:
KontRASt-03: A Phase Ib/II, Multicenter, Open-label Platform Study of JDQ443 With Select Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
This is Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select therapies in patients with advanced solid tumors harboring the KRAS G12C mutation.
Status | Recruiting |
Enrollment | 346 |
Est. completion date | June 16, 2027 |
Est. primary completion date | May 5, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: Dose Escalation: - Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care therapy or are ineligible to receive such therapy. Phase II: - Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer who have received platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy - Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer who have received fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, unless patient was ineligible to such therapy. All patients: - ECOG performance status of 0 or 1. - Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Exclusion Criteria: - Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations - Prior treatment with a KRAS G12C inhibitor is excluded for patients in a subset of groups in Phase II. - Active brain metastases, including symptomatic brain metastases or known leptomeningeal disease - Clinically significant cardiac disease or risk factors at screening - Insufficient bone marrow, hepatic or renal function at screening Other protocol-defined inclusion/exclusion criteria may apply |
Country | Name | City | State |
---|---|---|---|
Belgium | Novartis Investigative Site | Leuven | |
France | Novartis Investigative Site | Bordeaux | |
France | Novartis Investigative Site | Lyon | |
Germany | Novartis Investigative Site | Freiburg | |
Germany | Novartis Investigative Site | Ulm | |
Italy | Novartis Investigative Site | Milano | MI |
Korea, Republic of | Novartis Investigative Site | Seoul | |
Singapore | Novartis Investigative Site | Singapore | |
Spain | Novartis Investigative Site | Barcelona | Catalunya |
Spain | Novartis Investigative Site | Madrid | |
Spain | Novartis Investigative Site | Madrid | |
United States | Dana Farber Cancer Institute Dept.of DFCI | Boston | Massachusetts |
United States | Massachusetts General Hospital . | Boston | Massachusetts |
United States | NYU School of Medicine Langone Health | New York | New York |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
United States, Belgium, France, Germany, Italy, Korea, Republic of, Singapore, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Dose escalation: Incidence and severity of dose limiting toxicities (DLTs) of each combination treatment. | A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value that is not primarily related to disease, disease progression, intercurrent illness/injury, or concomitant medications that occurs within the first 28 days of study treatment and meets a defined criteria. | 28 days | |
Primary | Dose escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment | All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs). | 24 months | |
Primary | Dose escalation: Frequency of dose interruptions and reductions, by treatment | The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group. | 24 months | |
Primary | Dose Escalation: Dose intensity by treatment | Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response. | 24 months | |
Primary | PhaseII: Overall Response Rate by Blinded Independent Review Committee (BIRC) per RECIST 1.1 | ORR is the proportion of patients with a best overall response (BOR) of Complete Response (CR) or Partial Response (PR). | 24 months | |
Secondary | Dose escalation and Phase II: ORR by local review per RECIST 1.1 | ORR is the proportion of patients with a BOR of CR or PR. | 24 months | |
Secondary | Dose escalation and Phase II: Disease Control Rate (DCR) by local review per RECIST 1.1 | DCR is the proportion of patients with a BOR of CR or PR or Stable Disease (SD). The objective of this endpoint is to summarize patients with signs of "activity" defined as either shrinkage of tumor (regardless of duration) or slowing down of tumor growth. | 24 months | |
Secondary | Dose escalation and Phase II: Duration of Response (DoR) by local review per RECIST 1.1 | Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due any cause. | 24 months | |
Secondary | Dose escalation and Phase II: Progression-Free Survival (PFS) by local review per RECIST 1.1 | PFS is defined as the time from the date of start of treatment to the date of the first documented progression, or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. | 24 months | |
Secondary | Phase II: DCR by BIRC per RECIST 1.1 | DCR is the proportion of patients with a BOR of CR or PR or SD. The objective of this endpoint is to summarize patients with signs of "activity" defined as either shrinkage of tumor (regardless of duration) or slowing down of tumor growth. | 24 months | |
Secondary | Phase II: DoR by BIRC per RECIST 1.1 | Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due any cause. | 24 months | |
Secondary | Phase II: PFS by BIRC per RECIST 1.1 | PFS is defined as the time from the date of start of treatment to the date of the first documented progression, or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. | 24 months | |
Secondary | Phase II: Overall survival (OS) | OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive. | 24 months | |
Secondary | Dose escalation and Phase II: PK parameters - Maximum Concentration (Cmax), as applicable per arm | The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1) | 5 months | |
Secondary | Dose escalation and Phase II: PK parameters - Minimum Concentration (Cmin), as applicable per arm | Observed concentration at the end of a dosing interval (taken directly before next administration) | 5 months | |
Secondary | Dose escalation: Time to achieve Cmax - Tmax, as applicable per arm | The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) | 5 months | |
Secondary | Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCtau, as applicable per arm | The Area under curve calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1) | 5 months | |
Secondary | Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCinf, as applicable per arm | The AUC from time zero to infinity (mass x time x volume-1) | 5 months | |
Secondary | Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment | All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs). | 24 months | |
Secondary | Phase II: Frequency of dose interruptions and reductions, by treatment | The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group. | 24 months | |
Secondary | Phase II: Dose intensity by treatment | Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response. | 24 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05400122 -
Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer
|
Phase 1 | |
Active, not recruiting |
NCT05551052 -
CRC Detection Reliable Assessment With Blood
|
||
Completed |
NCT00098787 -
Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer
|
Phase 2 | |
Recruiting |
NCT06037954 -
A Study of Mental Health Care in People With Cancer
|
N/A | |
Recruiting |
NCT05425940 -
Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer
|
Phase 3 | |
Suspended |
NCT04595604 -
Long Term Effect of Trimodal Prehabilitation Compared to ERAS in Colorectal Cancer Surgery.
|
N/A | |
Completed |
NCT03414125 -
Effect of Mailed Invites of Choice of Colonoscopy or FIT vs. Mailed FIT Alone on Colorectal Cancer Screening
|
N/A | |
Completed |
NCT02963831 -
A Study to Investigate ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies
|
Phase 1/Phase 2 | |
Recruiting |
NCT05489211 -
Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)
|
Phase 2 | |
Terminated |
NCT01847599 -
Educational Intervention to Adherence of Patients Treated by Capecitabine +/- Lapatinib
|
N/A | |
Completed |
NCT05799976 -
Text Message-Based Nudges Prior to Primary Care Visits to Increase Care Gap Closure
|
N/A | |
Recruiting |
NCT03874026 -
Study of Folfiri/Cetuximab in FcGammaRIIIa V/V Stage IV Colorectal Cancer Patients
|
Phase 2 | |
Active, not recruiting |
NCT03170960 -
Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT03181334 -
The C-SPAN Coalition: Colorectal Cancer Screening and Patient Navigation
|
N/A | |
Completed |
NCT03167125 -
Participatory Research to Advance Colon Cancer Prevention
|
N/A | |
Recruiting |
NCT04258137 -
Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study
|
N/A | |
Recruiting |
NCT05568420 -
A Study of the Possible Effects of Medication on Young Onset Colorectal Cancer (YOCRC)
|
||
Recruiting |
NCT02972541 -
Neoadjuvant Chemotherapy Verse Surgery Alone After Stent Placement for Obstructive Colonic Cancer
|
N/A | |
Completed |
NCT02876224 -
Study of Cobimetinib in Combination With Atezolizumab and Bevacizumab in Participants With Gastrointestinal and Other Tumors
|
Phase 1 | |
Completed |
NCT01943500 -
Collection of Blood Specimens for Circulating Tumor Cell Analysis
|
N/A |