Solid Tumor, Colorectal Cancer, Cholangiocarcinoma, Bladder Cancer, Ovarian Cancer, Gastric Cancer, Palpable Subcutaneous Malignant Lesions, Renal Cell Carcinoma, Melanoma, Epithelial Ovarian Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer
Conditions
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, Pegylated liposomal doxorubicin (PLD), Carboplatin / PLD / Bevacizumab and Paclitaxel for selected advanced solid tumors.
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)PLD, 10) Carboplatin / PLD / Bevacizumab or 11) Paclitaxel 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.
Interventions
BIOLOGICALTRK-950
10 mg/kg administered intravenously over 60 minutes (weekly)
DRUGIrinotecan
Intravenously over 30 - 90 minutes
DRUGLeucovorin
Intravenously over 30 - 90 minutes
DRUG5-FU
Intravenously bolus and intravenously for two days
DRUGGemcitabine
Intravenously over 30 minutes
DRUGCisplatin
Intravenously over 60 minutes
DRUGCarboplatin
Intravenously per package insert
DRUGRamucirumab
Intravenously over 60 minutes
DRUGPaclitaxel
Intravenously
DRUGNivolumab
Intravenously over 30 minutes
DRUGPembrolizumab
Intravenously over 30 minutes
DRUGImiquimod Cream
Topically
DRUGBevacizumab
Intravenously over 90 minutes for the first dose, over 60 for the second dose and over 30 minutes for all subsequent doses
DRUGPLD
Intravenously over 60 minutes
Sponsors
Toray Industries, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of patients with laboratory abnormalities (Complete Blood Count, Coagulation, Urinalysis and Serum Chemistry) | 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 experiencing treatment emergent adverse events as assessed by CTCAE v5.0 | through study completion, an average of 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| 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) |
| 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 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) |
Countries
France, United States
Outcome results
None listed