Preoperative Administration of Olaparib With Cisplatin or With Durvalumab or Alone or no Tratment in Patients Who Are Candidates for Surgery of Carcinoma of the Head and Neck.

NCT02882308 | Completed Phase 2

• 2 other identifiers: HE5A/152015-005268-41
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

OPHELIA (OPHELIA (OlaParib and durvalumab in HEad and neck squamous celL carcInomA) trial is a Greek, investigator-initiated, randomized open-label window-of-opportunity phase II study. Patients with operable histologically documented squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx will be randomized between combination with durvalumab and olaparib, cisplatin and olaparib, monotherapy with olaparib or no treatment, before starting standard treatment.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Investigation of the change in the tumour Ki-67 before and after treatment with the combination of olaparib + durvalumab or olaparib + cisplatin or olaparib monotherapy.

  At baseline and at the day of the surgery or 2nd biopsy (at days 23-29 days)

Secondary Outcomes (23)

• Objective response rate according to RECIST 1.1 criteria

  Imaging studies will be performed at baseline and on week 4

• Pathologic complete response rate

  On week 4 only for operable patients

• Metabolic response rate assessed by FDG-PET/CT scan (optional)

  At baseline, on week 4

• Number of participants with tolerability to the treatment.

  From the 1st day of therapy and every week for 4 weeks maximum and 90 days after last therapy administration

• Surgical complication rate

  Up to 30 days after surgery or the day of initiation of the next anticancer therapy

Study Arms (4)

Monotherapy with olaparib

EXPERIMENTAL

Patients in the monotherapy arm will be treated with olaparib until the 21st -28th day depending on the day of surgery, will be reassessed by imaging (tumour objective response by RECIST) on the 22nd -28th day and then have a second biopsy or be operated on the 23rd - 29th day. If surgery is delayed, olaparib will be continued until the day before surgery.

Drug: Olaparib

Combination of cisplatin and olaparib

EXPERIMENTAL

Patients in the cisplatin - olaparib combination arm will receive treatment until the 5th day, will be reassessed by imaging (tumour objective response by RECIST) on the 22nd -28th day and then will have a second biopsy or be operated on the 23rd - 29th day.

Drug: Olaparib; Drug: Cisplatin

No treatment arm

NO INTERVENTION

Patients in the "no treatment" arm will wait to be operated or have a second biopsy on the 23rd - 29th day.Optionally, patients who have a baseline FDG-PET/CT scan may be re-examined on the 22nd -28th day by the same modality to assess metabolic response.

Combination of durvalumab and olaparib

EXPERIMENTAL

Patients in the durvalumab - olaparib combination arm will receive treatment until the 21th-28th day, will be reassessed by imaging (tumour objective response by RECIST) on the 22nd -28th day and then will have a second biopsy or be operated on the 23rd - 29th day. If surgery is delayed, olaparib will be continued until the day before surgery.

Drug: Olaparib; Drug: Durvalumab

Interventions

Olaparib DRUG

50/25 mg BD split x 5 days

Also known as: Lynparza

Combination of cisplatin and olaparib

Cisplatin DRUG

60 mg/m\^2 d1-d5

Also known as: Platamine

Combination of cisplatin and olaparib

Durvalumab DRUG

1500 mg d1

Also known as: Imfinzi

Combination of durvalumab and olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed written informed consent prior to any study specific procedures
• Female and/or male patients aged 18 years and over
• Body weight higher than 30 Kg
• Newly diagnosed histologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx
• Provision of biological material (tumor tissue and blood), provision of signed informed consent for translational research
• Patients selected for a primary surgical treatment
• No prior anti-cancer treatment for head and neck cancer
• Performance status ECOG 0-1
• Adequate hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥10g/dL
• Adequate renal function: serum creatinine level 1.5 mg/dl and Glomelular Filtration Rate50 ml/min by Cockroft/Gault formula
• Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase, AST (SGOT), ALT (SGPT) 5xULN
• No active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.
• Ability to swallow tablets.
• Regular follow-up feasible
• Baseline evaluations performed before registration: clinical and blood evaluations no more than 1 week (7 days) prior to registration, tumour assessment (CT or MRI scan of the head and neck, chest, abdomen and pelvis at the discretion of the investigator) no more than 30 days prior to registration

You may not qualify if:

• Metastatic or locally advanced unresectable disease
• Uncontrolled hypercalcemia
• Concomitant unplanned antitumour therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy)
• Treatment with any other investigational medicinal product within 28 days prior to study entry
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 30 days after the last dose of IMP.
• Treatment with CYP3A4 inhibitors as well as inducers, unless discontinued 7 days prior to randomization
• Other concomitant or previous malignancy, except: i) adequately treated in-situ carcinoma of the uterine cervix, ii) basal or squamous cell carcinoma of the skin, iii) cancer in complete remission for 5 years
• Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
• Pregnant or breastfeeding women
• Patients with known allergy to any excipients to study drugs
• History of myocardial infarction and/or stroke or other arterialthrombotic events or pulmonary embolism or unstable angina pectoris within 6 months prior to registration
• No features suggestive of myelodysplastic syndrome/ acute myeloid leukemia MDS/ AML
• Poorly controlled cardiac arrhythmias
• Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, bowel obstruction or inability to take oral medication

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead
• AstraZeneca: collaborator

Study Sites (2)

Euromedica General Clinic of Thessaloniki

Thessaloniki, Thessaloniki, 54645, Greece

Location

University Hospital "Attikon", 2nd Department of Internal Medicine, Division of Oncology

Athens, 12462, Greece

Location

Related Publications (1)

• Psyrri A, Gkotzamanidou M, Papaxoinis G, Krikoni L, Economopoulou P, Kotsantis I, Anastasiou M, Souliotis VL. The DNA damage response network in the treatment of head and neck squamous cell carcinoma. ESMO Open. 2021 Apr;6(2):100075. doi: 10.1016/j.esmoop.2021.100075. Epub 2021 Mar 10.

  PMID: 33714009 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

olaparib; Cisplatin; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Diamanto Psyrri, MD,Ass.Prof

  Division of Oncology, 2nd Dept of Internal Medicine, University Hospital "Attiko"

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: August 29, 2016
• Study Start: October 20, 2016
• Primary Completion: December 1, 2019
• Study Completion: January 10, 2020
• Last Updated: February 7, 2020

Record last verified: 2020-02

Locations

GR (2)