Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

TALazoparib and Avelumab as Maintenance Therapy in Platinum-Sensitive Metastatic or Locally Advanced URothelial Carcinoma (TALASUR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04678362
Recruitment Status : Recruiting
First Posted : December 21, 2020
Last Update Posted : June 7, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Centre Francois Baclesse

Brief Summary:
The main objectif is to determine the efficacy of a maintenance treatment combining Talazoparib and Avelumab after platinum-based chemotherapy in patients with locally advanced/metastatic urothelial carcinoma.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Drug: Talazoparib + Avelumab Phase 2

Detailed Description:

The first line treatment of urothelial carcinoma is a platinum-based chemotherapy. This treatment is efficient with a response rate > 50 % but the progression-free survival is short (7.7 months) and the chemotherapy is too toxic to be used in a prolonged time. Traditionally, maintenance chemotherapy refers to the utilization of regimens with less toxicity after the initial upfront treatment. This concept has already been efficient with PARP inhibitors in ovarian carcinoma and more recently with durvalumab in lung carcinoma.

The prevalence of somatic mutations in homologous recombination genes in UC as well as their association with platinum sensitivity suggests Talazoparib to be a target for a maintenance treatment of urothelial carcinoma. Moreover, there is a strong rational with both pre-clinical and clinical data to associate Avelumab and Talazoparib. This appears all the more relevant that Avelumab has already demonstrated its efficacy in urothelial carcinoma (after platinum-based chemotherapy failure).

In this context, the sponsorpropose a phase 2 study to assess the antitumor activity of the combination of Avelumab plus Talazoparib in metastatic urothelial carcinoma in maintenance therapy after platinum-based chemotherapy.

Considering the doubts about the best molecular predictive factors of Talazoparib and Avelumab, the sponsor willingly propose a non-selective study, without molecular screening. Tumors will be selected according to the platinum sensitivity which has the advantage to exclude poor prognosis tumors and will allow increasing the HRD tumor population.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single-arm phase 2 trial
Masking: None (Open Label)
Masking Description: None (open label=)
Primary Purpose: Treatment
Official Title: TALazoparib and Avelumab as Maintenance Therapy in Platinum-Sensitive Metastatic or Locally Advanced URothelial Carcinoma: A Single-arm Phase 2 Trial
Actual Study Start Date : June 1, 2021
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Talazoparib+avelumab
  • Talazoparib will be administered at the daily dose of 1 mg given orally in a 28-day cycle, except for patients with mild renal impairment (Creatinine clearance 30-59 mL/min) who will receive 0.75 mg per day.
  • Avelumab will be administered by intravenous (I.V.) route over 60 minutes at the dose of 800 mg on D1 and D15, in a 28-day cycle.
Drug: Talazoparib + Avelumab
Patients will receive the combined treatment until the investigator considers that the patient no longer obtains benefit from it. The treatment will be continued until disease progression, unacceptable toxicity or discontinuation for any cause.




Primary Outcome Measures :
  1. The progression-free survival [ Time Frame: 7 months ]

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 18 months ]
  2. Duration of tumoral response [ Time Frame: 18 months ]


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.


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

Inclusion Criteria:

  • Patient ≥18 years at the day of consenting to the study
  • Provision of informed consent prior to any study specific procedures
  • Histologically confirmed diagnosis of urothelial carcinoma of the renal pelvis, ureter (upper urinary tract), bladder or urethra. Both transitional cell and mixed transitional/non-transitional cell histologies are allowed, but transitional cell carcinoma must be the predominant histology.
  • Documented Stage IV disease (T4b, N0, M0; any T, N1-N3, M0; any T, any N, M1) not candidate to a curative treatment with surgery or radiotherapy at the start of first-line platinum-based chemotherapy.
  • Patient must have completed prior to inclusion a platinum-based (cisplatin or carboplatin) polychemotherapy for at least 4 cycles of chemotherapy (until 6 cycles maximum) and have a stable disease or a partial response (PR) or a complete response (CR) from the chemotherapy according to RECIST 1.1 criteria

    • A minimum dose of 55 mg/m² of cisplatin is required in order to count for 1 cycle.
  • A minimum dose of carboplatin AUC 4.5 is required in order to count for 1 cycle
  • Eligibility based on this criterion will be established locally by the investigator by examining pre and post-chemotherapy radiological assessments (CT/MRI)
  • Neoadjuvant or adjuvant chemotherapy is allowed (with a delay of at least 12 months between the last dose of neoadjuvant or adjuvant chemotherapy and the relapse)
  • Patient must be enrolled within 8 weeks after the last dose of chemotherapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
  • Normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
  • Hemoglobin ≥ 10.0 g/dL (patient may have been transfused before inclusion)
  • Absolute neutrophil count (ANC) ≥1.5 x 109/L
  • Platelet count ≥100 G/l
  • Total bilirubin ≤1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤2.5 x ULN unless liver metastases are present in which case they must be ≤5x ULN
  • Patient must have creatinine clearance estimated using the CKD equation of ≥ 40 mL/min
  • Able to swallow and retain oral drug
  • Life expectancy > 12 weeks
  • Serum pregnancy test (for females of childbearing potential) negative at screening
  • Male patient able to father children and female patient of childbearing potential and at risk for pregnancy must agree to use 2 highly effective methods of contraception throughout the study and for at least 60 days after the last dose of treatments
  • Patient affiliated to a French Social Security System or a beneficiary of such a system
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
  • Optional: provision of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block (or subsection thereof) from the most recent primary or metastatic tumor biopsy

Exclusion Criteria:

  • Patient who has never received chemotherapy with a platinum salt (cisplatin or carboplatin) for advanced/metastatic urothelial carcinoma
  • Patient who has previously received more than one line of chemotherapy for advanced/metastatic urothelial carcinoma
  • Patient whose disease has progressed according to RECIST v1.1 criteria after the first line platinum-based chemotherapy for urothelial carcinoma. The cancer must not be in the progression phase at inclusion
  • Patient with known CNS metastases and/or carcinomatous meningitis
  • Other malignancy within the last 3 years except: adequately treated non-melanoma, skin cancer curatively treated, in situ cancer of the cervix, ductal carcinoma in situ (DCIS), localized prostate carcinoma without PSA relapse
  • Patient with myelodysplastic syndrome/acute myeloid leukemia history or with features suggestive of MDS/AML
  • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patient with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are allowed.Current treatment with an immunosuppressant medicinal product or treatment within 7 days prior to inclusion, EXCEPT:

    • Intra-nasal, inhaled or local steroids or local steroid injections (such as intra-articular injections)
    • Systemic corticosteroids at physiological doses of ≤ 10 mg/day of prednisone or equivalent
    • Steroids as premedication for hypersensitivity reactions (such as CT scan premedication)
  • Major surgery within 4 weeks or major radiotherapy within to starting experimental treatment. Previous palliative radiotherapy (≤ 10 fractions) for metastatic lesions is permitted provided that this has been completed at least one week prior to starting Talazoparib and Avelumab
  • Active viral infection (HIV, Hepatitis B/C) or known history of positive test for HIV
  • Any previous treatment with PARP inhibitor or any immunotherapy (e.g. anti-CTLA-4 or anti-PDL1/ PD1)
  • Concomitant treatment with any drug on the prohibited medication list such as live vaccines, concomitant use of strong P-gp inhibitors (cf section "Prohibited concomitant treatments") or systemic corticoids at dose > 10 mg/day prednisone or equivalent. Live vaccines administered more than 30 days before study entry are permitted
  • Clinically significant (e.g. active) cardiovascular disease cerebral vascular accident/stroke in the 3 months prior to enrollment: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (≥ New York Heart Association Classification Class II), serious cardiac arrhythmia requiring medication, uncontrolled high blood pressure, cerebrovascular accident, transient ischaemic attack
  • Patient considered at poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease or any psychiatric disorder that prohibits obtaining informed consent
  • Pulmonary embolism or deep vein thrombosis within 3 months prior to inclusion (unless if stable, asymptomatic and treated with a low molecular heparin for at least 10 days prior to starting Talazoparib + Avelumab).
  • Pregnant or lactating woman;
  • Participation in another interventional study with a systemic anti-cancer treatment within 4 weeks prior to inclusion. Inclusion in observational or interventional studies not involving a health product is permitted. Patient with telephone follow up of toxicities and simple laboratory monitoring or other questionnaires alone may be included.
  • Patient unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication;Previous organ transplant including stem cell allotransplantation or double umbilical cord blood transplantation.
  • Patient with a known hypersensitivity to Talazoparib and Avelumab or any of the excipients of the product.
  • People who are vulnerable under the law (minors, adults under legal protection, people deprived of their freedom)
  • Other persisting toxicities related to previous anticancer treatments: "Persisting toxicity related to prior therapy (NCI CTCAE Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable."

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): NCT04678362


Locations
Layout table for location information
France
Institut de Cancérologie de l'Ouest Recruiting
Angers, France
Contact: Elouen BOUGHALEM, MD    +33 2 41 35 28 92    elouen.boughalem@ico.unicancer.fr   
Principal Investigator: Elouen BOUGHALEM, MD         
CHU Jean Minjoz Not yet recruiting
Besançon, France
Contact: Thiery VUILLEMIN, MD         
Principal Investigator: Thiery VUILLEMIN, MD         
Centre François baclesse Active, not recruiting
Caen, France, 14000
Centre Jean Perrin Not yet recruiting
Clermont-Ferrand, France
Contact: Hakim MAHAMMEDI, MD         
Principal Investigator: Hakim MAHAMMEDI, MD         
Centre George-François Leclerc Not yet recruiting
Dijon, France
Contact: Sylvain LADOIRE, MD         
Principal Investigator: Sylvain LADOIRE, MD         
Centre Léon Bérard Not yet recruiting
Lyon, France
Contact: Aude FLECHON, MD         
Principal Investigator: Aude FLECHON, MD         
Institut de Cancérologie de l'Ouest Not yet recruiting
Nantes, France
Contact: Elouen BOUGHALEM, MD         
Principal Investigator: Elouen BOUGHALEM, MD         
Centre Antoine Lacassagne Not yet recruiting
Nice, France
Contact: Delphine BORCHIELLINI, MD         
Principal Investigator: Delphine BORCHIELLINI, MD         
Croix Saint-Simon Diaconesses Active, not recruiting
Paris, France
Hopital Tenon Not yet recruiting
Paris, France
Contact: Ahmed KHALIL, MD         
Principal Investigator: Ahmed KHALIL, MD         
Centre Eugène Marquis Active, not recruiting
Rennes, France
IUCT Active, not recruiting
Toulouse, France
Sponsors and Collaborators
Centre Francois Baclesse
Pfizer
Layout table for additonal information
Responsible Party: Centre Francois Baclesse
ClinicalTrials.gov Identifier: NCT04678362    
Other Study ID Numbers: 2020-001105-24
First Posted: December 21, 2020    Key Record Dates
Last Update Posted: June 7, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Avelumab
Talazoparib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action