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Trial record 39 of 283 for:    Tumor infiltrating lymphocytes

Checkpoint Inhibitors Assessment in Oropharynx Carcinoma (CIAO)

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ClinicalTrials.gov Identifier: NCT03144778
Recruitment Status : Recruiting
First Posted : May 9, 2017
Last Update Posted : November 5, 2018
Sponsor:
Collaborators:
AstraZeneca
Stiefel, a GSK Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

Objectives:

Primary Objective The study primary objective is to access the differences between CD8+ tumor infiltrating lymphocytes evaluated by immunohistochemistry staining in the post-treatment surgical specimens as compared to baseline in patients treated with durvalumab single agent compared with patients receiving durvalumab plus tremelimumab.

Secondary Objectives

The secondary objectives of this study are to assess:

Safety and toxicity of durvalumab single agent or combined with tremelimumab administered every 4 weeks for 2 doses in the preoperative setting according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Objective Response rate at 8 weeks, as determined by RECIST 1.1

Percentage of patients undergoing the initially proposed surgery at 4 weeks

Percentage of patients undergoing the initially proposed surgery at 8 weeks

Percentage of viable tumor cells in the surgical specimen

Patient-reported outcomes (PRO) during treatment with checkpoint inhibitors


Condition or disease Intervention/treatment Phase
Malignant Neoplasms of Oropharynx Drug: Durvalumab Drug: Tremelimumab Behavioral: Questionnaire Procedure: Surgery Drug: Chemotherapy Radiation: Radiation Therapy Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Checkpoint Inhibitors Assessment in Oropharynx Carcinoma (CIAO)
Actual Study Start Date : July 12, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Cohort 1 - Durvalumab

Participants receive Durvalumab every 28 days for a total of 2 doses.

Symptom questionnaire completed on Day 1, Day 29, Day 5, 42 days after surgery or, if receiving standard-of-care chemotherapy/radiation therapy, within 7 days before starting the regimen, 6 months after surgery, 24 months, and 5 years after surgery.

Surgery performed as part of standard of care between Days 57 and 71.

After surgery, upon decision of physician, additional standard of care chemotherapy and/or radiation may be given.

Drug: Durvalumab
1500 mg (equivalent to 20 mg/Kg) in patients > 30 Kg by vein for a total of 2 doses on Day 1 and Day 29.
Other Name: MEDI4736

Behavioral: Questionnaire
Symptom questionnaire completed on Day 1, Day 29, Day 5, 42 days after surgery or, if receiving standard-of-care chemotherapy/radiation therapy, within 7 days before starting the regimen, 6 months after surgery, 24 months, and 5 years after surgery.
Other Name: Survey

Procedure: Surgery
Standard of care surgery performed preferably no earlier than 8 weeks and no later than 10 weeks after the first administration of the investigational agents.

Drug: Chemotherapy
Post-operative chemotherapy delivered at the best judgment of the treating physicians, preferably within 6 weeks of surgical resection.

Radiation: Radiation Therapy
Post-operative radiation therapy delivered at the best judgment of the treating physicians, preferably within 6 weeks of surgical resection.
Other Name: XRT

Experimental: Cohort 2 - Durvalumab + Tremelimumab

Participants receive Durvalumab plus Tremelimumab every 28 days for a total of 2 doses.

Symptom questionnaire completed on Day 1, Day 29, Day 5, 42 days after surgery or, if receiving standard-of-care chemotherapy/radiation therapy, within 7 days before starting the regimen, 6 months after surgery, 24 months, and 5 years after surgery.

Surgery performed as part of standard of care between Days 57 and 71.

After surgery, upon decision of physician, additional standard of care chemotherapy and/or radiation may be given.

Drug: Durvalumab
1500 mg (equivalent to 20 mg/Kg) in patients > 30 Kg by vein for a total of 2 doses on Day 1 and Day 29.
Other Name: MEDI4736

Drug: Tremelimumab
75 mg (equivalent to 1 mg/kg Q4W) for 2 doses in patients >30 kg by vein for a total of 2 doses on Day 1 and Day 29.
Other Names:
  • Ticilimumab
  • CP-675,206

Behavioral: Questionnaire
Symptom questionnaire completed on Day 1, Day 29, Day 5, 42 days after surgery or, if receiving standard-of-care chemotherapy/radiation therapy, within 7 days before starting the regimen, 6 months after surgery, 24 months, and 5 years after surgery.
Other Name: Survey

Procedure: Surgery
Standard of care surgery performed preferably no earlier than 8 weeks and no later than 10 weeks after the first administration of the investigational agents.

Drug: Chemotherapy
Post-operative chemotherapy delivered at the best judgment of the treating physicians, preferably within 6 weeks of surgical resection.

Radiation: Radiation Therapy
Post-operative radiation therapy delivered at the best judgment of the treating physicians, preferably within 6 weeks of surgical resection.
Other Name: XRT




Primary Outcome Measures :
  1. Change of CD8+ Tumor Infiltrating Lymphocytes of Durvalumab Single Agent or Combined with Tremelimumab [ Time Frame: Baseline and 6 months after surgery ]
    Primary endpoint is the change of CD8+ tumor infiltrating lymphocytes before and after treatment, defined as the ratio of the CD8+ lymphocytes density in the post-treatment surgical specimens over the CD8+ density in the baseline biopsy before treatment.


Secondary Outcome Measures :
  1. Adverse Events of Durvalumab Single Agent or Combined with Tremelimumab [ Time Frame: 8 weeks ]
    Adverse events assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  2. Objective Response Rate (ORR) of Durvalumab Single Agent or Combined with Tremelimumab [ Time Frame: 8 weeks ]
    Objective response rate (ORR) assessed by RECIST 1.1.



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Written informed consent to participate in the study according to the investigational review board (IRB)
  2. Suspected or histologically/cytologically confirmed OPSCC, stage II, III, or IVA (according to the AJCC 7th edition), or patients with loco-regional recurrence from an OPSCC primary, if time of recurrence is at least 6 months after completion of initial curative intent treatment (surgery or radiotherapy +/- chemotherapy or cetuximab). Patients with a suspected lesion may be enrolled and a baseline biopsy will be obtained as part of the study. If squamous cell histology is not confirmed, patients will be discontinued from the study
  3. Patients must have surgically resectable disease in the opinion of the treating physician. For patients with a primary OPSCC, patients must be eligible for TORS (Transoral Robotic Surgery)
  4. Available tissue from prior biopsy (minimum of 10 unstained slides), or willing to undergo core biopsy to obtain tumor material. Biopsy will be mandatory for patients with recurrent disease
  5. Age >/= 18 years at time of study entry
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  7. Adequate normal organ and marrow function as defined below: Haemoglobin >/= 9.0 g/dL Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L (> 1500 per mm^3) Platelet count >/= 100 x 10^9/L (>100,000 per mm^3) Serum bilirubin </=1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician AST /ALT </= 2.5 x institutional upper limit of normal Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) /72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 / 72 x serum creatinine (mg/dL)
  8. Patients with reproductive potential (e.g., females menopausal for less than 1 year and not surgically sterilized) must practice two highly effective contraceptive measures for the duration of study drug therapy and for at least 90 days after completion of durvalumab monotherapy or for at least 180 days after completion of durvalumab/tremelimumab combination therapy. Female patients of childbearing potential must provide a negative pregnancy test (urine) prior to treatment initiation.
  9. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

  1. Histology other than squamous cell carcinoma
  2. Primary site other than oropharynx
  3. Prior systemic therapy (chemotherapy, biologic, or immunotherapy) for the same OPSCC. Prior chemotherapy, biologic therapy, and radiotherapy is allowed in patients with loco-regional recurrent disease, if administered at least 6 months prior to study enrolment
  4. Previous treatment with Anti-CTLA-4 including tremelimumab or PD1/PD-L1 inhibitor, including durvalumab
  5. History of another primary malignancy except for: (i) OPSCC with loco-regional recurrence after 6 months of curative-intent treatment and amenable to salvage surgery; (ii) malignancy treated with curative intent and with no evidence of active disease >/= 2 years before the first dose of study drug and of low potential risk for recurrence; (iii) non-melanoma, skin cancer or lentigo maligna; in situ cervical, breast, prostate or bladder carcinoma
  6. Any concurrent anticancer therapy
  7. Mean QT interval corrected for heart rate (QTc) >/= 470 ms calculated from a baseline electrocardiogram using Fredericia's Correction.
  8. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid , and single dose of dexamethasone of up to 20 mg (or equivalent corticosteroid) administered prior to diagnostic or baseline study biopsy of the oropharynx, as per institution standard of care.
  9. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
  10. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or pneumonitis
  11. History of primary immunodeficiency
  12. History of allogeneic organ transplant
  13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, seizures, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  14. Known history of active tuberculosis
  15. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab
  16. Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing two highly effective methods of birth control
  17. Any medical or psychosocial condition that will interfere with evaluation of study treatment or interpretation of patient safety or study results
  18. Known allergy or hypersensitivity to IP or any excipient
  19. Any unresolved grade 2 or higher toxicity from previous anti-cancer therapy.
  20. Primary tumor not amenable to TORS

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): NCT03144778


Contacts
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Contact: Renata Ferrarotto, MD 713-792-6363 rferrarotto@mdanderson.org

Locations
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United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       rferrarotto@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
AstraZeneca
Stiefel, a GSK Company
Investigators
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Principal Investigator: Renata Ferrarotto, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03144778     History of Changes
Other Study ID Numbers: 2016-0805
NCI-2018-01199 ( Registry Identifier: NCI CTRP )
First Posted: May 9, 2017    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: November 2018

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

Keywords provided by M.D. Anderson Cancer Center:
Malignant Neoplasms of Oropharynx
CD8+ tumor infiltrating lymphocytes
Biomarkers
Durvalumab
MEDI4736
Tremelimumab
Ticilimumab
CP-675,206

Additional relevant MeSH terms:
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Neoplasms
Oropharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Durvalumab
Ipilimumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs