A Study of TRK-950 in Combinations With Anti-Cancer Treatment Regimens in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
The main purpose of this study is to establish the safety and the recommended dose of TRK-950 in combination with FOLFIRI, Gemcitabine / Cisplatin, Gemcitabine / Carboplatin, Ramucirumab / Paclitaxel, PD1 inhibitors (Nivolumab or Pembrolizumab), and Imiquimod Cream, Bevacizumab, Gemcitabine / Carboplatin / Bevacizumab, Topotecan, and Pegylated liposomal doxorubicin (PLD) for selected advanced solid tumors.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed Description
This study is an open-label, Phase 1b study evaluating TRK-950 in combination with 1) FOLFIRI or 2) Gemcitabine / Cisplatin or 3) Gemcitabine / Carboplatin or 4) Ramucirumab/Paclitaxel or 5) PD1 inhibitors (Nivolumab or Pembrolizumab) or 6) Imiquimod Cream for subcutaneous lesions 7) Bevacizumab 8) Gemcitabine / Carboplatin / Bevacizumab, 9) Topotecan, or 10) PLD in Patients with Selected Advanced Solid Tumors. The objectives of this study are to determine the safety, tolerability, MTD, recommended Phase 2 dose (RP2D), PK, and preliminary anti-tumor activity of TRK-950 when used in combination with other treatment regimens.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm A: TRK-950 + FOLFIRI Colorectal Cancer TRK-950 will be administered intravenously (IV) on days 1, 8, 15, and 22 of a 28-day cycle. On days 1 and 15 Irinotecan will be administered IV. Leucovorin will be infused to match the duration of the irinotecan infusion. 5-FU will be administered as IV bolus, followed by TRK-950 administration. After the TRK-950, 5-FU will be administered by a continuous infusion. |
Biological: TRK-950
Intravenously over 60 minutes
Drug: Irinotecan
Intravenously over 30 - 90 minutes
Drug: Leucovorin
Intravenously over 30 - 90 minutes
Drug: 5-FU
Intravenously bolus and intravenously for two days
|
Experimental: Arm B: TRK-950 + Gemcitabine/Cisplatin Cholangiocarcinoma or Bladder Cancer TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on days 1 and 8, Cisplatin will be administered by infusion. Then, Gemcitabine will be administered as an IV infusion. |
Biological: TRK-950
Intravenously over 60 minutes
Drug: Gemcitabine
Intravenously over 30 minutes
Drug: Cisplatin
Intravenously over 60 minutes
|
Experimental: Arm C: TRK-950 + Gemcitabine/Carboplatin Ovarian Cancer TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on days 1 and 8, Gemcitabine will be administered as an intravenous infusion. On day 1, following the administration of TRK-950 and Gemcitabine, Carboplatin will be administered IV. |
Biological: TRK-950
Intravenously over 60 minutes
Drug: Gemcitabine
Intravenously over 30 minutes
Drug: Carboplatin
Intravenously per package insert
|
Experimental: Arm D: TRK-950 + Ramucirumab/Paclitaxel Gastric Cancer TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Ramucirumab will be administered as an IV infusion. Paclitaxel will be dosed on days 1, 8 and 15, after the Ramucirumab on days 1 and 15 and after the TRK-950 on day 8. |
Biological: TRK-950
Intravenously over 60 minutes
Biological: Ramucirumab
Intravenously over 60 minutes
Drug: Paclitaxel
Intravenously
|
Experimental: Arm E: TRK-950 + PD1 inhibitors •Solid Tumors E-1: TRK-950 + Nivolumab •TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Nivolumab will be administered as an IV infusion. E-2: TRK-950 + Pembrolizumab •TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on day 1, Pembrolizumab will be administered as an IV infusion. |
Biological: TRK-950
Intravenously over 60 minutes
Biological: Nivolumab
Intravenously over 30 minutes
Biological: Pembrolizumab
Intravenously over 30 minutes
|
Experimental: Arm F: TRK-950 + Imiquimod Cream Palpable subcutaneous malignant lesions TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. Imiquimod cream is to be applied 5 of 7 days in a row with 2 days rest for a maximum of 2 cycles (total 6 weeks). |
Biological: TRK-950
Intravenously over 60 minutes
Drug: Imiquimod Cream
Topically
|
Experimental: Arm G: TRK-950 + Bevacizumab Renal Cell Carcinoma TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Bevacizumab will be administered as an IV infusion. |
Biological: TRK-950
Intravenously over 60 minutes
Biological: Bevacizumab
Intravenously over 90 minutes for the first dose, over 60 for the second dose and over 30 minutes for all subsequent doses
|
Experimental: Arm H: TRK-950 + PD1 inhibitors •Melanoma H-1: TRK-950 + Nivolumab •TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Nivolumab will be administered as an IV infusion. H-2: TRK-950 + Pembrolizumab •TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on day 1, Pembrolizumab will be administered as an IV infusion. |
Biological: TRK-950
Intravenously over 60 minutes
Biological: Nivolumab
Intravenously over 30 minutes
Biological: Pembrolizumab
Intravenously over 30 minutes
|
Experimental: Arm J: TRK-950 + FOLFIRI Colorectal Cancer TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. On days 1 and 15 Irinotecan will be administered IV. Leucovorin will be infused to match the duration of the irinotecan infusion. 5-FU will be administered as IV bolus, followed by TRK-950 administration. After the TRK-950, 5-FU will be administered by a continuous infusion. |
Biological: TRK-950
Intravenously over 60 minutes
Drug: Irinotecan
Intravenously over 30 - 90 minutes
Drug: Leucovorin
Intravenously over 30 - 90 minutes
Drug: 5-FU
Intravenously bolus and intravenously for two days
|
Experimental: Arm K: TRK-950(Lower-dose) + Gemcitabine / Carboplatin / Bevacizumab Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. On all dosing days, TRK-950 will be administered IV after the relevant combination regimen is dosed. Gemcitabine will be administered as an intravenous infusion on days 1 and 8. On day 1, following the administration of Gemcitabine, Carboplatin will be administered as an intravenous infusion. Also on Day 1 of each cycle, Bevacizumab will be administered IV next. After 6 cycles of chemotherapy the patient will be transitioned to maintenance treatment. On Day 1 of each maintenance cycle, Bevacizumab will be administered IV. Maintenance treatment will be continued as long as there is no evidence of progressive disease. |
Biological: TRK-950
Intravenously over 60 minutes
Drug: Gemcitabine
Intravenously over 30 minutes
Drug: Carboplatin
Intravenously per package insert
Biological: Bevacizumab
Intravenously over 90 minutes for the first dose, over 60 for the second dose and over 30 minutes for all subsequent doses
|
Experimental: Arm L: TRK-950 + Gemcitabine / Carboplatin / Bevacizumab Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. On all dosing days, TRK-950 will be administered IV after the relevant combination regimen is dosed. Gemcitabine will be administered as an intravenous infusion on days 1 and 8. On day 1, following the administration of Gemcitabine, Carboplatin will be administered as an intravenous infusion. Also on Day 1 of each cycle, Bevacizumab will be administered IV next. After 6 cycles of chemotherapy the patient will be transitioned to maintenance treatment. On Day 1 of each maintenance cycle, Bevacizumab will be administered IV. Maintenance treatment will be continued as long as there is no evidence of progressive disease. |
Biological: TRK-950
Intravenously over 60 minutes
Drug: Gemcitabine
Intravenously over 30 minutes
Drug: Carboplatin
Intravenously per package insert
Biological: Bevacizumab
Intravenously over 90 minutes for the first dose, over 60 for the second dose and over 30 minutes for all subsequent doses
|
Experimental: Arm M: TRK-950(Lower-dose) + Topotecan Platinum Resistant epithelial ovarian, primary peritoneal or fallopian tube cancer TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. Topotecan will be administered as an intravenous infusion daily for 5 consecutive days of a 21 day cycle. On day 1 TRK-950 will be administered IV after the topotecan infusion. |
Biological: TRK-950
Intravenously over 60 minutes
Drug: Topotecan
Intravenously over 30 minutes
|
Experimental: Arm O: TRK-950(Lower-dose) + PLD Platinum Resistant epithelial ovarian, primary peritoneal or fallopian tube cancer TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. PLD will be dosed as IV on Day 1 of each cycle. On days that TRK-950 and PLD are both dosed, PLD will be dosed first. |
Biological: TRK-950
Intravenously over 60 minutes
Drug: PLD
Intravenously over 60 minutes
|
Experimental: Arm Q: TRK-950(Lower-dose) +Ramucirumab/Paclitaxel Gastric cancer TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. On all dosing days, TRK-950 will be administered IV after the relevant combination regimen is dosed. On days 1 and 15, ramucirumab will be administered IV. Paclitaxel will be dosed on days 1, 8 and 15, after ramucirumab on days 1 and 15, before TRK-950 on day 8. |
Biological: TRK-950
Intravenously over 60 minutes
Biological: Ramucirumab
Intravenously over 60 minutes
Drug: Paclitaxel
Intravenously
|
Experimental: Arm R: TRK-950(Lower-dose) +Bevacizumab Renal cell carcinoma cancer TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. Bevacizumab will be dosed as IV on Day 1 and 15 of each cycle. On days that TRK-950 and Bevacizumab are both dosed, Bevacizumab will be dosed first. |
Biological: TRK-950
Intravenously over 60 minutes
Biological: Bevacizumab
Intravenously over 90 minutes for the first dose, over 60 for the second dose and over 30 minutes for all subsequent doses
|
Outcome Measures
Primary Outcome Measures
- Frequency of patients experiencing treatment emergent adverse events as assessed by CTCAE v5.0 [through study completion, an average of 1 year]
- Blood pressure [through study completion, an average of 1 year]
mmHg
- Heart rate [through study completion, an average of 1 year]
bpm
- Respiratory rate [through study completion, an average of 1 year]
bpm
- Temperature [through study completion, an average of 1 year]
°F or °C
- Weight [through study completion, an average of 1 year]
lbs/kg
- Height [through study completion, an average of 1 year]
inches/cm
- Performance status using Karnofsky performance status criteria [through study completion, an average of 1 year]
- QTc interval determined from 12-lead Electrocardiogram [through study completion, an average of 1 year]
msec
- QRS interval determined from 12-lead Electrocardiogram [through study completion, an average of 1 year]
msec
- Frequency of patients with laboratory abnormalities (Complete Blood Count, Coagulation, Urinalysis and Serum Chemistry) [through study completion, an average of 1 year]
Secondary Outcome Measures
- Overall response rate (ORR) [through study completion, an average of 1 year]
- Disease Control Rate (DCR) [through study completion, an average of 1 year]
- Serum concentration of TRK-950 [through study completion, an average of 1 year]
- Plasma concentration of Gemcitabine for the first six patients in Arm K [At the beginning of Cycle 1 and Cycle 4 (each cycle is 21 days)]
- Plasma concentration of Carboplatin for the first six patients in Arm K [At the beginning of Cycle 1 and Cycle 4 (each cycle is 21 days)]
- Serum concentration of Bevacizumab for the first six patients in Arm K [At the beginning of Cycle 1, Cycle 2, Cycle 4 and Cycle 5 (each cycle is 21 days)]
- Plasma concentration of Topotecan for the first six patients in Arm M [At the beginning of Cycle 1 and Cycle 3 (each cycle is 21 days)]
- Plasma concentration of PLD for the first six patients in Arm O [At the beginning and middle of Cycle 1 and Cycle 3 (each cycle is 28 days)]
- Serum concentration of Ramucirumab for the first six patients in Arm Q [At the beginning and middle of Cycle 1 and Cycle 4 (each cycle is 28 days)]
- Plasma concentration of Paclitaxel for the first six patients in Arm Q [At the beginning of Cycle 1 and Cycle 4 (each cycle is 28 days)]
- Serum concentration of Bevacizumab for the first six patients in Arm R [At the beginning and middle of Cycle 1 and Cycle 4 (each cycle is 28 days)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed solid malignancy for which the following treatment regimens are warranted:
-
Arm A. Colorectal Cancer with no prior history of treatment with Irinotecan alone or in combination: FOLFIRI as standard of care
-
Arm B. Cholangiocarcinoma, Bladder Cancer with no prior history of treatment with Gemcitabine alone or in combination: Gemcitabine / Cisplatin as standard of care
-
Arm C and Expansion Cohort 1. Ovarian Cancer who have relapsed at least 6 or more months after completion of a previous platinum-based therapy and have no prior history of treatment with gemcitabine alone or in combination: Gemcitabine / Carboplatin as standard of care
-
Arm D and Expansion Cohort 2. Gastric Cancer including Gastroesophageal Junction with no prior history of treatment with Ramucirumab, Paclitaxel or any Taxane class drug: Ramucirumab / Paclitaxel as standard of care
-
Arm E. Solid Tumors: Eligible for PD1 Inhibitor (Nivolumab or Pembrolizumab) monotherapy as standard of care according to the approved drug label by the relevant regulatory authority
-
Arm F. Locally advanced or metastatic disease in a cancer with at least one palpable subcutaneous malignant lesion (≤ 2 cm in diameter) for treatment with TRK-950 and Imiquimod cream (US Sites Only)
-
Arm G. Renal Cell Carcinoma with no prior history of treatment with Bevacizumab alone or in combination: Bevacizumab for use in a fourth line or later treatment
-
Arm H. Melanoma patients who progressed while taking Nivolumab, Pembrolizumab, or Ipilimumab, within the last 6 months prior to cycle 1 day 1
-
Arm J. Colorectal Cancer patients who progressed on FOLFIRI or any other Irinotecan-containing therapy regimen within the last 6 months prior to cycle 1 day 1
-
Arm K. (US Sites Only). Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer with ≤ 2 prior treatment lines who have recurred > 6 months after most recent platinum-based chemotherapy and who are eligible for gemcitabine, carboplatin, and Bevacizumab as standard of care for dosing of TRK-950(Lower-dose)
-
Arm L. (US Sites Only). Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer with ≤ 2 prior treatment lines who have recurred > 6 months after most recent platinum-based chemotherapy and who are eligible for gemcitabine, carboplatin, and Bevacizumab as standard of care for dosing of TRK-950
-
Arms M and O. Platinum Resistant epithelial ovarian, primary peritoneal or fallopian tube cancer with ≤ 5 prior treatment regimens, as defined below and who are eligible for topotecan or pegylated liposomal doxorubicin as standard of care for dosing of TRK-950(Lower-dose)
-
Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response, and then progressed between 3 months and less than or equal to 6 months after the last date of platinum.
-
Patients who have received 2 to 5 lines of prior therapy must have received at least 4 cycles of platinum and then progressed within 6 months after the date of the last dose of platinum.
-
Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy
-
Arm Q. Gastric Cancer including GEJ cancer with only 1 prior treatment regimen, which recurred during or within 4 months after frontline treatment, and no prior history of treatment with Ramucirumab, Paclitaxel or any Taxane class drug for metastatic disease: eligible to receive Ramucirumab/Paclitaxel as standard of care (Lower-dose)
-
Arm R. Clear cell renal cell carcinoma with no prior history of treatment with Bevacizumab alone or in combination: Bevacizumab for use in a fourth line or later treatment. (Lower-dose)
-
Primary or metastatic tumors measurable per RECIST v1.1 on CT scan or by calipers (subcutaneous lesions)
-
Karnofsky performance of ≥70
-
Life expectancy of at least 3 months
-
Age ≥ 18 years
-
Signed, written IRB-approved informed consent
Exclusion Criteria:
-
Laboratory values or medications that are contraindicated in the selected standard of care treatment regimens
-
New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
-
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Prophylactic antibiotics are acceptable.
-
Pregnant or nursing women
-
Treatment with radiation therapy within 2 weeks, or treatment with surgery, chemotherapy, immunotherapy, or investigational therapy within four weeks prior to initiation of study treatment (6 weeks for nitrosoureas or mitomycin C, and 2 weeks or 5 half-lives whichever is longer for TKIs).
-
Unwillingness or inability to comply with procedures required in this protocol
-
Known active infection with HIV, hepatitis B, hepatitis C
-
Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
-
Patients who are currently receiving any other investigational agent
-
Any contraindicated condition or drug which would make the patient ineligible for the respective treatment regimen that is to be used in combination with TRK-950 (for example, autoimmune disorders for nivolumab or pembrolizumab treatment) as described in the Full Prescribing Information
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | HonorHealth Research Institute | Scottsdale | Arizona | United States | 85258 |
2 | AOA-HOPE | Tucson | Arizona | United States | 85711 |
3 | USC Norris Comprehensive Cancer Center | Los Angeles | California | United States | 90033 |
4 | HOAG Memorial Hospital Presbyterian | Newport | California | United States | 92663 |
5 | Ochsner Clinic Foundation | New Orleans | Louisiana | United States | 70121 |
6 | Atlantic Health System | Morristown | New Jersey | United States | 07960 |
7 | Perlmutter Cancer Center at NYU Langone | New York | New York | United States | 10016 |
8 | Oncology Associates of Oregon, P.C.(Willamette Valley Cancer Institute and Research Center) | Eugene | Oregon | United States | 97401 |
9 | Northwest Cancer Specialists | Portland | Oregon | United States | 97227 |
10 | Texas Oncology, P.A. Baylor Charles A. Sammons Cancer Center | Dallas | Texas | United States | 75246 |
11 | Virginia Cancer Specialists, PC | Leesburg | Virginia | United States | 20176 |
12 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
13 | Centre Léon Bérard | Lyon | France | 69373 |
Sponsors and Collaborators
- Toray Industries, Inc
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 950P1V02