Active, not recruiting
Phase 1
A Study of TRK-950 in Combinations With Anti-Cancer Treatment Regimens in Patients With Advanced Solid Tumors
Condition(s) studied
Solid TumorColorectal CancerCholangiocarcinomaBladder CancerOvarian CancerGastric CancerPalpable Subcutaneous Malignant LesionsRenal Cell CarcinomaMelanomaEpithelial Ovarian CancerPrimary Peritoneal CancerFallopian Tube Cancer
Investigational drug(s) / intervention(s)
TRK-950TRK-950TRK-950IrinotecanLeucovorin5-FUGemcitabineCisplatinCarboplatinRamucirumabPaclitaxelNivolumabPembrolizumabImiquimod CreamBevacizumabPLD
TRK-950: 10 mg/kg administered intravenously over 60 minutes (weekly)
TRK-950: 5 mg/kg administered intravenously over 60 minutes (weekly)
TRK-950: Treatment Phase: 20 mg/kg administered intravenously over 60 minutes (bi-weekly) Maintenance Phase: 30 mg/kg administered intravenously over 60 minutes (every 3 weeks)
Irinotecan: Intravenously over 30 - 90 minutes
Leucovorin: Intravenously over 30 - 90 minutes
5-FU: Intravenously bolus and intravenously for two days
Gemcitabine: Intravenously over 30 minutes
Cisplatin: Intravenously over 60 minutes
Carboplatin: Intravenously per package insert
Ramucirumab: Intravenously over 60 minutes
Paclitaxel: Intravenously
Nivolumab: Intravenously over 30 minutes
Pembrolizumab: Intravenously over 30 minutes
Imiquimod Cream: Topically
Bevacizumab: Intravenously over 90 minutes for the first dose, over 60 for the second dose and over 30 minutes for all subsequent doses
PLD: Intravenously over 60 minutes
Study 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, Pegylated liposomal doxorubicin (PLD), Carboplatin / PLD / Bevacizumab and Paclitaxel for selected advanced solid tumors.
Eligibility
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. 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. 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
* Arm 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
* 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
* 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.
* Arm S. Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer with ≤ 2 prior treatment lines who have recurred \> 182 days after most recent platinum-based chemotherapy and who are eligible for carboplatin, PLD, and bevacizumab as standard of care
* The histological subtypes of the carcinoma that qualify for enrollment include serous adenocarcinoma, endometrioid adenocarcinoma, carcinosarcoma of the ovary, or adenocarcinoma not otherwise specified (NOS)
* Patients with or without the breast cancer susceptibility 1/2 (BRCA1/2) mutations are eligible, provided that patients with the BRCA1/2 mutations have previously received PARP inhibitor treatment
* Arm T. Platinum Resistant epithelial ovarian, primary peritoneal or fallopian tube cancer with ≤ 5 prior treatment regimens, or as defined below, and who are eligible for paclitaxel as standard of care
* 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 (complete response/remission (CR) or partial response/remission (PR), and then progressed between 90 days to less than 183 days after the last date of platinum.
* Patients who have received multiple lines of platinum therapy must have progressed on the latest platinum, or within 183 days after the date of the last dose of the latest platinum
* Patients with or without the BRCA1/2 mutations are eligible, provided that patients with the BRCA1/2 mutations have previously received PARP inhibitor treatment
* Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy
* The histological subtypes of the carcinoma that qualify for enrollment include serous adenocarcinoma, endometrioid adenocarcinoma, carcinosarcoma of the ovary, or adenocarcinoma not otherwise specified (NOS)
* 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, targeted therapy 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
Primary outcome measure(s)
- Frequency of patients experiencing treatment emergent adverse events as assessed by CTCAE v5.0 — through study completion, an average of 1 year
- Frequency of patients experiencing adverse events of special interest (AESIs) — 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
Trial sites (14)
| Facility | City | Region | Status |
| HonorHealth Research Institute |
Scottsdale |
Arizona |
|
| AOA-HOPE |
Tucson |
Arizona |
|
| USC Norris Comprehensive Cancer Center |
Los Angeles |
California |
|
| HOAG Memorial Hospital Presbyterian |
Newport |
California |
|
| Ochsner Clinic Foundation |
New Orleans |
Louisiana |
|
| Atlantic Health System |
Morristown |
New Jersey |
|
| Perlmutter Cancer Center at NYU Langone |
New York |
New York |
|
| Oncology Associates of Oregon, P.C.(Willamette Valley Cancer Institute and Research Center) |
Eugene |
Oregon |
|
| Northwest Cancer Specialists |
Portland |
Oregon |
|
| Texas Oncology, P.A. Baylor Charles A. Sammons Cancer Center |
Dallas |
Texas |
|
| Texas Oncology - Downtown Fort Worth Cancer Center |
Fort Worth |
Texas |
|
| Virginia Cancer Specialists, PC |
Leesburg |
Virginia |
|
| Medical College of Wisconsin |
Milwaukee |
Wisconsin |
|
| Centre Léon Bérard |
Lyon |
France |
|
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