Checkpoint Inhibitors Assessment in Oropharynx Carcinoma (CIAO)

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 28
• Participant gender: All

Summary

The goal of this clinical research study is to learn if giving durvalumab alone or in combination with tremelimumab to patients with oropharynx carcinoma before standard-of-care surgery can help to control the disease.

The safety of these drugs will also be studied.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: AstraZeneca
• Treatments: Antibodies, Monoclonal; Tremelimumab
• Last Updated: 2017-06-20

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 bilirubinof 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 /ALTcreatinine 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

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