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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-003952-19 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: 1st line colorectal cancer | Experimental | Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab |
|
| Cohort B: 2nd line colorectal cancer | Experimental | Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab |
|
| Cohort C: 2nd line gastroesophageal cancer | Experimental | Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab |
|
| Cohort D: 2nd or 3rd line renal cell carcinoma | Experimental | Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gevokizumab | Drug | 60 mg/mL concentration; administered intravenously (IV) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1a/b (Cohorts A and B): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy | Log scale change of hs-CRP at Day 15 from baseline | Baseline, Day 15 |
| Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D] | 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. | First 4 weeks of combination treatment |
| Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B] | 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. | First 6 weeks of combination treatment |
| Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level] | 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. | At 15 months |
| Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level] | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall response rate (ORR) per investigator assessment using RECIST v1.1 | 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 | Up to 5 years |
| Duration of response (DOR) per investigator assessment using RECIST v1.1 |
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Key Inclusion Criteria:
For All Cohorts:
For Cohort A:
• First line metastatic colorectal adenocarcinoma.
For Cohort B:
• Second line metastatic colorectal adenocarcinoma that has progressed on prior line of chemotherapy administered for metastatic disease and which must include a fluoropyrimidine and oxaliplatin.
For Cohort C:
• Second line metastatic gastroesophageal adenocarcinoma 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:
For subjects starting from Part 2 in Cohort C:
• Serum hs CRP at screening ≥ 10 mg/L (per central laboratory assessment).
Key Exclusion Criteria:
For All Cohorts:
For Cohort D:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California LA | Los Angeles | California | 90095 | United States | ||
| WA Uni School Of Med |
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| Label | URL |
|---|---|
| Novartis Pharma AG results | View source |
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
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|
| Bevacizumab | Drug | 25 mg/mL concentration; administered IV |
|
| Modified FOLFOX6 | Drug | Oxaliplatin [5 mg/mL concentration; administered IV], leucovorin [10 mg/mL concentration; administered IV] (or levoleucovorin [10 mg/mL concentration; administered IV]), and 5-fluorouracil [50 mg/mL concentration; administered IV] |
|
|
| FOLFIRI | Drug | Irinotecan [20 mg/mL concentration; administered IV], leucovorin [10 mg/mL concentration; administered IV] (or levoleucovorin [10 mg/mL concentration; administered IV]), and 5-fluorouracil [50 mg/mL concentration; administered IV] |
|
|
| Ramucirumab | Drug | 10 mg/mL concentration; administered IV |
|
| Paclitaxel | Drug | 6 mg/mL concentration; administered IV |
|
| Cabozantinib | Drug | 60 mg tablet; administered orally |
|
| At 9 months |
| Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level] | 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. | At 6 months |
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 |
| Up to 5 years |
| Disease Control Rate (DCR) per investigator assessment using RECIST v1.1 | DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1. | Up to 5 years |
| Overall survival (OS) | OS is defined as the time from date of first dose of study treatment to date of death due to any cause. | Up to 5 years |
| PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level] | 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. | Up to 5 years |
| PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B) | 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. | Up to 5 years |
| Number of patients with anti-drug antibodies for gevokizumab in the combination regimens | Incidence of immunogenicity for gevokizumab | Up to 5 years |
| St Louis |
| Missouri |
| 63110 |
| United States |
| Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| Novartis Investigative Site | Melbourne | Victoria | 3000 | Australia |
| Novartis Investigative Site | Brussels | 1000 | Belgium |
| Novartis Investigative Site | Edegem | 2650 | Belgium |
| Novartis Investigative Site | Leuven | 3000 | Belgium |
| Novartis Investigative Site | Calgary | Alberta | T2N4N2 | Canada |
| Novartis Investigative Site | Toronto | Ontario | M5G 2M9 | Canada |
| Novartis Investigative Site | Santiago | Santiago Metropolitan | 8330074 | Chile |
| Novartis Investigative Site | Brno | 656 53 | Czechia |
| Novartis Investigative Site | Frankfurt am Main | Hesse | 60488 | Germany |
| Novartis Investigative Site | Dresden | Saxony | 01307 | Germany |
| Novartis Investigative Site | Ulm | 89081 | Germany |
| Novartis Investigative Site | Ramat Gan | 5265601 | Israel |
| Novartis Investigative Site | Tel Aviv | 6423906 | Israel |
| Novartis Investigative Site | Milan | MI | 20162 | Italy |
| Novartis Investigative Site | Rozzano | MI | 20089 | Italy |
| Novartis Investigative Site | Nagoya | Aichi-ken | 464 8681 | Japan |
| Novartis Investigative Site | Kashiwa | Chiba | 2778577 | Japan |
| Novartis Investigative Site | Osaka | Osaka | 5418567 | Japan |
| Novartis Investigative Site | Sunto Gun | Shizuoka | 411 8777 | Japan |
| Novartis Investigative Site | Bunkyo-ku | Tokyo | 113-8603 | Japan |
| Novartis Investigative Site | Singapore | 119074 | Singapore |
| Novartis Investigative Site | Seoul | 05505 | South Korea |
| Novartis Investigative Site | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain |
| Novartis Investigative Site | Madrid | 28009 | Spain |
| Novartis Investigative Site | Madrid | 28034 | Spain |
| Novartis Investigative Site | Madrid | 28050 | Spain |
| Novartis Investigative Site | Seville | 41013 | Spain |
| Novartis Investigative Site | Valencia | 46010 | Spain |
| Novartis Investigative Site | Tainan | 704302 | Taiwan |
| Novartis Investigative Site | London | SW3 6JJ | United Kingdom |
| Novartis Investigative Site | Manchester | M20 2BX | United Kingdom |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D002292 | Carcinoma, Renal Cell |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C547697 | gevokizumab |
| D000068258 | Bevacizumab |
| D000077150 | Oxaliplatin |
| D002955 | Leucovorin |
| D005472 | Fluorouracil |
| C480833 | IFL protocol |
| D000077146 | Irinotecan |
| D000096662 | Ramucirumab |
| D017239 | Paclitaxel |
| C558660 | cabozantinib |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
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