A Study of TRK-950 in Combinations With Anti-Cancer Treatment Regimens in Patients With Advanced Solid Tumors

A Phase 1b, Multicenter Study to Determine the Dose, Safety, Efficacy and Pharmacokinetics of TRK-950 When Used in Combinations With Selected Anti-Cancer Treatment Regimens in Patients With Selected Advanced Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Renal Cell Carcinoma; Gastric Cancer; Colorectal Cancer; Ovarian Cancer; Fallopian Tube Cancer; Solid Tumor; Cholangiocarcinoma; Bladder Cancer; Epithelial Ovarian Cancer; Primary Peritoneal Cancer; Palpable Subcutaneous Malignant Lesions
• Intervention / Treatment: Drug: Irinotecan; Drug: Leucovorin; Drug: 5-FU; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Imiquimod Cream; Drug: PLD; Biological: TRK-950; Biological: TRK-950; Biological: TRK-950; Drug: Ramucirumab; Drug: Nivolumab; Drug: Pembrolizumab; Drug: Bevacizumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 187
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Vicki Bauernschub, BSN, RN; Phone Number: 602 358 8324; Email: vbauernschub@td2inc.com

Study Locations

• France
  • Lyon, France, 69373
    • Recruiting
    • Centre Léon Bérard
    • Contact: Philippe Cassier, M.D.; Phone Number: +33 (0)4 26 55 68 33
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • HonorHealth Research Institute
      • Contact: Joyce Schaffer, MSN,RN,AOCNS; Phone Number: 480-323-1339
    • Tucson, Arizona, United States, 85711
      • Recruiting
      • AOA-HOPE
      • Contact: AOA-HOPE; Phone Number: 520-886-0206
      • Contact: Julie Klinker, BSN; Phone Number: (520)269-3821; Email: Julie.klinker@usoncology.com
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC Norris Comprehensive Cancer Center
      • Contact: Xiomara Menendez, BSN, RN; Phone Number: 323-409-4368; Email: Xiomara.Menendez@med.usc.edu
    • Newport, California, United States, 92663
      • Recruiting
      • Hoag Memorial Hospital Presbyterian
      • Contact: Chi Nguyen, CCRP; Phone Number: 949-764-6763; Email: chi.nguyen@hoag.org
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Recruiting
      • Ochsner Clinic Foundation
      • Contact: Amanda Woolery, RN; Email: Amanda.woolery@ochsner.org
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Recruiting
      • Atlantic Health System
      • Contact: Angela Alistar, Dr.; Phone Number: 973-971-7960; Email: Angela.Alistar@atlantichealth.org
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • Perlmutter Cancer Center at NYU Langone
      • Contact: Priyanka Patel, BS; Email: Priyanka.Patel@nyulangone.org
      • Contact: Brianne Boljonis, BSN,RN; Email: Brianne.Boljonis@nyulangone.org
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Recruiting
      • Oncology Associates of Oregon, P.C.(Willamette Valley Cancer Institute and Research Center)
      • Contact: Oncology Associates of Oregon, P.C.; Phone Number: 541-683-5001
      • Contact: Jeanne Schaffer, RN-BSN; Email: Jeanne.Schaffer@usoncology.com
    • Portland, Oregon, United States, 97227
      • Recruiting
      • Northwest Cancer Specialists
      • Contact: Northwest Cancer Specialists; Phone Number: 503-528-5005
      • Contact: Amber Holden, BA; Phone Number: (360)597-1300; Email: amber.holden@compassoncology.com
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology, P.A. Baylor Charles A. Sammons Cancer Center
      • Contact: Texas Oncology, P.A.; Phone Number: 214-370-1000
      • Contact: Rita Lopez, AS; Phone Number: (214)584-3236; Email: rita.lopez2@usoncology.com
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Texas Oncology - Downtown Fort Worth Cancer Center
      • Contact: Nori Sullivan, RN, BSN, CCRC; Phone Number: 817-413-1760; Email: nori.sullivan@usoncology.com
  • Virginia
    • Leesburg, Virginia, United States, 20176
      • Recruiting
      • Virginia Cancer Specialists, Pc
      • Contact: Virginia Cancer Specialists, PC; Phone Number: 703-554-6800
      • Contact: Carrie Friedman, Research Nurse Navigator; Phone Number: (703)636-1473; Email: carrie.friedman@usoncology.com
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Completed
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

  o 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)

• 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
  • 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

15

Arms and Interventions

Participant Group / 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.	Drug: Irinotecan; Intravenously over 30 - 90 minutes; Drug: Leucovorin; Intravenously over 30 - 90 minutes; Drug: 5-FU; Intravenously bolus and intravenously for two days; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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)
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.	Drug: Gemcitabine; Intravenously over 30 minutes; Drug: Cisplatin; Intravenously over 60 minutes; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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)
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.	Drug: Gemcitabine; Intravenously over 30 minutes; Drug: Carboplatin; Intravenously per package insert; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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)
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.	Drug: Paclitaxel; Intravenously; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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); Drug: Ramucirumab; Intravenously over 60 minutes
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; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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); Drug: Nivolumab; Intravenously over 30 minutes; Drug: 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).	Drug: Imiquimod Cream; Topically; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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)
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; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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); Drug: 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; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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); Drug: Nivolumab; Intravenously over 30 minutes; Drug: 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.	Drug: Irinotecan; Intravenously over 30 - 90 minutes; Drug: Leucovorin; Intravenously over 30 - 90 minutes; Drug: 5-FU; Intravenously bolus and intravenously for two days; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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)
Experimental: Arm K: 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.	Drug: Gemcitabine; Intravenously over 30 minutes; Drug: Carboplatin; Intravenously per package insert; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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); Drug: 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 O: TRK-950 + 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.	Drug: PLD; Intravenously over 60 minutes; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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)
Experimental: Arm Q: TRK-950 + 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.	Drug: Paclitaxel; Intravenously; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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); Drug: Ramucirumab; Intravenously over 60 minutes
Experimental: Arm R: TRK-950 + 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; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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); Drug: 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 S: TRK-950 + Carboplatin / PLD/ Bevacizumab; Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer; Treatment Phase: TRK-950 will be administered IV on days 1 and 15 of a 28-day cycle. Carboplatin will be administered as an intravenous infusion on day 1. On day 1, following the administration of Carboplatin, PLD will be administered as an intravenous infusion. Also on Day 1 of each cycle, Bevacizumab will be administered IV next. On days 1 and 15, TRK-950 will be administered IV after the Bevacizumab infusion. • Maintenance Phase: 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. Following the Bevacizumab administration, TRK-950 will be administered IV. Maintenance treatment will be continued as long as there is no evidence of progressive disease.	Drug: Carboplatin; Intravenously per package insert; Drug: PLD; Intravenously over 60 minutes; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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); Drug: 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 T: TRK-950 + Paclitaxel; 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. On days 1, 8 and 15 of each cycle, Paclitaxel will be dosed on IV	Drug: Paclitaxel; Intravenously; Biological: TRK-950; 10 mg/kg administered intravenously over 60 minutes (weekly); Biological: TRK-950; 5 mg/kg administered intravenously over 60 minutes (weekly); Biological: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	mmHg	through study completion, an average of 1 year
Heart rate	bpm	through study completion, an average of 1 year
Respiratory rate	bpm	through study completion, an average of 1 year
Temperature	°F or °C	through study completion, an average of 1 year
Weight	lbs/kg	through study completion, an average of 1 year
Height	inches/cm	through study completion, an average of 1 year
Performance status using Karnofsky performance status criteria		through study completion, an average of 1 year
QTc interval determined from 12-lead Electrocardiogram	msec	through study completion, an average of 1 year
QRS interval determined from 12-lead Electrocardiogram	msec	through study completion, an average of 1 year
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

Outcome Measure	Time Frame
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)
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)

Collaborators and Investigators

• Sponsor: Toray Industries, Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2019
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: March 7, 2019
• First Submitted That Met QC Criteria: March 11, 2019
• First Posted (Actual): March 13, 2019

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Kidney Neoplasms; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma, Renal Cell; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Cholangiocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Adjuvants, Immunologic; Vitamins; Immune Checkpoint Inhibitors; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Interferon Inducers; Carboplatin; Nivolumab; Bevacizumab; Pembrolizumab; Leucovorin; Irinotecan; Ramucirumab; Imiquimod; Gemcitabine
• Other Study ID Numbers: 950P1V02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No