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Trial record 2 of 2 for:    TSR-042

Study of Niraparib or Carboplatin-Paclitaxel in Combination With TSR-042 or With TSR-042 and Bevacizumab

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ClinicalTrials.gov Identifier: NCT03307785
Recruitment Status : Recruiting
First Posted : October 12, 2017
Last Update Posted : February 12, 2018
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Brief Summary:

Part A: To test the safety and tolerability of combination therapy with Niraparib and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part B: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part C: To test the safety and tolerability of combination therapy with Niraparib, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study.

Part D: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study.


Condition or disease Intervention/treatment Phase
Metastatic Cancer Advanced Cancer Solid Tumor Drug: Niraparib Drug: TSR-042 Drug: Carboplatin-Paclitaxel Drug: Bevacizumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b Dose-Finding Study of Niraparib, Niraparib/Bevacizumab, Carboplatin-Paclitaxel, or Carboplatin-Paclitaxel/Bevacizumab in Combination With TSR-042 in Patients With Advanced or Metastatic Cancer
Actual Study Start Date : October 12, 2017
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A: Dose Finding
Test safety and tolerability of combination therapy of Niraparib with TSR-042. To establish a Phase 2 dose (RP2D)
Drug: Niraparib
Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for patients with tumors that harbor defects in the homologous recombination DNA repair pathway or that are driven by PARP-mediated transcription factors.
Other Name: Zejula

Drug: TSR-042
TSR-042 is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).

Experimental: Part B: Safety and Tolerability Evaluation
Test the safety and tolerability of combination therapy of Carboplatin-Pacitaxel with TSR-042. To establish a Phase 2 dose (RP2D)
Drug: TSR-042
TSR-042 is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).

Drug: Carboplatin-Paclitaxel
Carboplatin in combination with paclitaxel is a chemotherapy treatment that has been shown to be efficacious against a variety of different tumor types, including non-small cell lung cancer [NSCLC], ovarian cancer, endometrial cancer, and head and neck cancer.

Experimental: Part C: Dose Finding
Test safety and tolerability of combination therapy of Niraparib and Bevacizumab with TSR-042. To establish a Phase 2 dose (RP2D)
Drug: Niraparib
Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for patients with tumors that harbor defects in the homologous recombination DNA repair pathway or that are driven by PARP-mediated transcription factors.
Other Name: Zejula

Drug: TSR-042
TSR-042 is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).

Drug: Bevacizumab
Bevacizumab is a chemotherapy treatment that has been shown to be efficacious against a variety of different cancer types, including colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. Bevacizumab is in the angiogenesis inhibitor and monoclonal antibody families of medication. It works by slowing the growth of new blood vessels.
Other Name: Avastin

Experimental: Part D: Safety and Tolerability Evaluation
Test the safety and tolerability of combination therapy of Carboplatin-Pacitaxel and Bevaxizumab with TSR-042. To establish a Phase 2 dose (RP2D)
Drug: TSR-042
TSR-042 is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).

Drug: Carboplatin-Paclitaxel
Carboplatin in combination with paclitaxel is a chemotherapy treatment that has been shown to be efficacious against a variety of different tumor types, including non-small cell lung cancer [NSCLC], ovarian cancer, endometrial cancer, and head and neck cancer.

Drug: Bevacizumab
Bevacizumab is a chemotherapy treatment that has been shown to be efficacious against a variety of different cancer types, including colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. Bevacizumab is in the angiogenesis inhibitor and monoclonal antibody families of medication. It works by slowing the growth of new blood vessels.
Other Name: Avastin




Primary Outcome Measures :
  1. Safety and tolerability of TSR 042 and niraparib combination treatment using Common Terminology Criteria for Adverse Events (CTCAE v.4.03) in patients with advanced or metastatic cancer [ Time Frame: Part A: Safety and Tolerability Evaluation - Approximately 2-Years ]
  2. Establish a recommended Phase 2 dose (RP2D) [ Time Frame: Part A: Dose Finding - Approximately 2-Years ]
  3. Safety and tolerability of TSR-042 and carboplatin-paclitaxel combination treatment using Common Terminology Criteria for Adverse Events (CTCAE v.4.03) in patients with advanced or metastatic cancer [ Time Frame: Part B: Safety and Tolerability Evaluation - Approximately 2-Years ]
  4. Establish a recommended Phase 2 dose (RP2D) [ Time Frame: Part B: Dose Finding - Approximately 2-Years ]
  5. Safety and tolerability of TSR 042, niraparib and bevacizumab combination treatment using Common Terminology Criteria for Adverse Events (CTCAE v.4.03) in patients with advanced or metastatic cancer [ Time Frame: Part C: Safety and Tolerability Evaluation - Approximately 2-Years ]
  6. Establish a recommended Phase 2 dose (RP2D) [ Time Frame: Part C: Dose Finding - Approximately 2-Years ]
  7. Safety and tolerability of TSR 042, carboplatin-paclitaxel and bevacizumab combination treatment using Common Terminology Criteria for Adverse Events (CTCAE v.4.03) in patients with advanced or metastatic cancer [ Time Frame: Part D: Safety and Tolerability Evaluation - Approximately 2-Years ]
  8. Establish a recommended Phase 2 dose (RP2D) [ Time Frame: Part D: Dose Finding - Approximately 2-Years ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  2. Duration of response (DOR) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  3. Disease control rate (DCR) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  4. Progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  5. Anti-Drug Antibodies (ADA) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
    To evaluate anti-drug antibodies (ADAs) of TSR-042 during TSR-042 and niraparib combination treatment or TSR-042 and carboplatin-paclitaxel combination treatment or TSR-042, niraparib and bevacizumab combination treatment or TSR-042, carboplatin-pacitaxel and bevacizumab combination treatment

  6. PK Parameter: AUC, 0-last assessment [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  7. PK Parameter: AUC, 0 to infinity [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  8. PK Parameter: AUC at steady state [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  9. PK Parameter: Minimum Concentration (Cmin) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  10. PK Parameter: Maximum Concentration (Cmax) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  11. PK Parameter: Clearance (CL) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  12. PK Parameter: Cmin at steady state (Cmin,ss) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  13. PK Parameter: Cmax at steady state (Cmax, ss) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  14. PK Parameter: Volume of Distribution (Vz) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]
  15. PK Parameter: terminal half-life (t1/2) [ Time Frame: Part A, Part B, Part C and Part D - Approximately 4 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has histologically or cytologically proven advanced (unresectable) or metastatic cancer as outlined below according to study part and disease type:
  • Part A: Patients with previously treated advanced or metastatic cancer. Patient may have received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal treatment will not be considered a prior line of treatment.
  • Part B: Patients with advanced or metastatic cancer for which treatment with carboplatin-paclitaxel is considered appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will not be considered a prior line of treatment.
  • Part C: Patients with previously treated advanced or metastatic cancer. Patient may have received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal treatment will not be considered a prior line of treatment.
  • Part D: Patients in whom carboplatin-paclitaxel and bevacizumab is considered appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will not be considered a prior line of treatment.
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Patient has adequate organ function
  • Female patient has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential.
  • Male patient agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study treatment through 90 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
  • Patient has measurable lesions by RECIST v1.1.

For Part A and C, in addition to the general inclusion criteria, patients must also meet the following additional criterion to be considered eligible to participate in this study:

  • Patient is able to take oral medications.
  • For patients to be eligible for any parts of the study using niraparib 300 mg as a starting dose, a screening actual body weight ≥ 77 kg and screening platelet count ≥ 150,000 u/L is necessary.

Exclusion Criteria:

(Patients will not be eligible for the study entry if any of the following criteria are met)

  • Patient has known active central nervous system metastases, carcinomatous meningitis, or both.
  • Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
  • Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection that requires systemic therapy.
  • Patient has a condition (such as transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation
  • Patient is pregnant or expecting to conceive children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of study treatment.

Note: No data are available regarding the presence of niraparib or its metabolites in human milk, or on its effects on the breastfed infant or milk production. Because of the potential for serious adverse reactions in breastfed infants from niraparib, female patients should not breastfeed during treatment with niraparib and for 1 month after receiving the final dose.

  • Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
  • Patient has known active hepatitis B or hepatitis C.
  • Patient has an active autoimmune disease that has required systemic treatment in the past 2 years.
  • Patient has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Patient has undergone prior treatment with a known PARP inhibitor.
  • Known history or current diagnosis of MDS or AML.

For Parts C and D only, patients will not be eligible for study entry if the following additional exclusion criterion is met:

  • Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident [CVA]) within 6 months of enrollment.
  • Patient has a history of bowel obstruction, including subocclusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.
  • Patient has proteinuria as demonstrated by urine protein: creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate <2 g of protein in 24 hours to be eligible).
  • Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
  • Patient has a known hypersensitivity to bevacizumab components or excipients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03307785


Contacts
Contact: Beth Zharoff, Director, Patient Focused Clinical Trial Engagement 781-209-5485 bzaharoff@tesarobio.com

Locations
United States, Arizona
Honor Health Recruiting
Scottsdale, Arizona, United States, 85258
Principal Investigator: Jasgit Sachdev, MD         
United States, California
California Cancer Associates for Research and Excellence (cCare) Recruiting
Encinitas, California, United States, 92024
Principal Investigator: Alberto Bessudo, MD         
United States, Florida
Florida Cancer Specialist Recruiting
Sarasota, Florida, United States, 34232
Principal Investigator: Manish Patel, MD         
United States, Ohio
Gabrail Cancer Center Research Recruiting
Canton, Ohio, United States, 44718
Principal Investigator: Nashat Gabrail, MD         
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Erika Hamilton, MD         
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Timothy Yap, MD         
Sponsors and Collaborators
Tesaro, Inc.

Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT03307785     History of Changes
Other Study ID Numbers: 3000-01-002
First Posted: October 12, 2017    Key Record Dates
Last Update Posted: February 12, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes
Paclitaxel
Niraparib
Albumin-Bound Paclitaxel
Bevacizumab
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors