Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers
- Conditions
- Colorectal CancerGastroesophageal CancerRenal Cell Carcinoma
- Interventions
- Drug: Modified FOLFOX6Drug: FOLFIRI
- Registration Number
- NCT03798626
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This study will determine the pharmacodynamically-active dose of gevokizumab and the tolerable dose of gevokizumab in combination with the standard of care anti-cancer therapy in patients with metastatic colorectal cancer, metastatic gastroesophageal cancer and metastatic renal cell carcinoma, and the preliminary efficacy of gevokizumab in combination with the SOC anti-cancer therapy in subjects with mCRC and mGEC.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 167
- Metastatic disease not amenable to potentially curative surgery and with available archival tumor tissue or fresh tumor tissue biopsy.
- Presence of at least 1 measurable lesion assessed by CT and/or MRI according to RECIST 1.1.
For Cohort A:
- First line metastatic colorectal cancer.
For Cohort B:
- Second line metastatic colorectal cancer that has progressed on prior chemotherapy administered for metastatic disease and which must include a fluoropyrimidine and oxaliplatin.
For Cohort C:
- Second line metastatic gastroesophageal cancer that has progressed on prior line of chemotherapy administered for metastatic disease, and which must include a platinum agent and fluoropyrimidine doublet.
For Cohort D:
- Second or third line metastatic renal cell carcinoma with a clear-cell component and has received one or two lines of treatment for metastatic disease that included an anti-angiogenic agent for at least 4 weeks with radiologic progression on that treatment.
For subjects starting from Part 1a in Cohorts A and B:
- Serum hs-CRP at screening ≥ 10 mg/L.
- Not requiring immediate initiation of anti-cancer therapy per investigator's best judgement.
For subjects starting from Part 2 in Cohort C:
- Serum hs-CRP at screening ≥ 10 mg/L.
For All Cohorts:
- Currently receiving any of the prohibited medications or has contraindications as outlined in the protocol.
- Symptomatic brain metastases or brain metastases that require directed therapy (such as focal radiotherapy or surgery).
- Suspected or proven immunocompromised state, or infections (as defined in the protocol).
- Conditions that have a high risk of clinically significant bleeding after administration of anti-VEGF agents.
- Clinically significant, uncontrolled or recent (within last 6 months) cardiovascular disease.
For Cohort D:
- Concomitant medications, herbal supplements, and/or fruits and their juices that are known as strong inhibitors or inducers of CYP3A4/5, and medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
- Impairment of GI function or GI disease that may significantly alter the absorption of cabozantinib.
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: 1st line colorectal cancer Modified FOLFOX6 Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab Cohort B: 2nd line colorectal cancer FOLFIRI Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab Cohort C: 2nd line gastroesophageal cancer Gevokizumab Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab Cohort A: 1st line colorectal cancer Gevokizumab Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab Cohort B: 2nd line colorectal cancer Gevokizumab Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab Cohort A: 1st line colorectal cancer Bevacizumab Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab Cohort C: 2nd line gastroesophageal cancer Ramucirumab Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab Cohort C: 2nd line gastroesophageal cancer Paclitaxel Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab Cohort B: 2nd line colorectal cancer Bevacizumab Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab Cohort D: 2nd or 3rd line renal cell carcinoma Gevokizumab Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib Cohort D: 2nd or 3rd line renal cell carcinoma Cabozantinib Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib
- Primary Outcome Measures
Name Time Method Part 1a (Dose finding): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy Baseline, Day 15 Log scale change of hs-CRP at Day 15 from baseline
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level] At 6 months PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D] First 4 weeks of combination treatment DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.
Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B] First 6 weeks of combination treatment DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level] At 15 months PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level] At 9 months PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
- Secondary Outcome Measures
Name Time Method Serum concentration of gevokizumab, as monotherapy and in the combination regimens Up to 5 years To characterize the pharmacokinetics of gevokizumab therapy
Number of patients with anti-drug antibodies for bevacizumab in the combination regimens Up to 5 years Incidence of immunogenicity for bevacizumab
Overall response rate (ORR) per investigator assessment using RECIST v1.1 Up to 5 years ORR is defined as the proportion of subjects with best overall response (BOR) of complete response (CR) or partial response (PR), according to RECIST 1.1
PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B) Up to 5 years PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.
Serum concentration of irinotecan Up to 3 months To characterize the pharmacokinetics of irinotecan therapy
Serum concentration of paclitaxel Up to 3 months To characterize the pharmacokinetics of paclitaxel therapy
Number of patients with anti-drug antibodies for ramucirumab in the combination regimens Up to 5 years Incidence of immunogenicity for ramucirumab
Serum concentration of ramucirumab Up to 5 years To characterize the pharmacokinetics of ramucirumab therapy
Serum concentration of cabozantinib Up to 3 months To characterize the pharmacokinetics of cabozantinib therapy
Overall survival (OS) Up to 5 years OS is defined as the time from date of first dose of study treatment to date of death due to any cause.
PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level] Up to 5 years PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.
Duration of response (DOR) per investigator assessment using RECIST v1.1 Up to 5 years Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death due to any cause, according to RECIST 1.1 criteria
Disease Control Rate (DCR) per investigator assessment using RECIST v1.1 Up to 5 years DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1.
Serum concentration of bevacizumab Up to 5 years To characterize the pharmacokinetics of bevacizumab therapy
Number of patients with anti-drug antibodies for gevokizumab in the combination regimens Up to 5 years Incidence of immunogenicity for gevokizumab
Trial Locations
- Locations (4)
University of California LA
🇺🇸Los Angeles, California, United States
WA Uni School Of Med
🇺🇸Saint Louis, Missouri, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Novartis Investigative Site
🇬🇧Manchester, United Kingdom