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Squamous Cell Carcinoma of the Head and NeckPhase 2OPHELIANCT02882308

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.

A Phase 2 study testing Olaparib, Cisplatin and Durvalumab in people with Squamous Cell Carcinoma of the Head and Neck, run by Hellenic Cooperative Oncology Group at 2 sites in Greece.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Olaparib, Cisplatin and Durvalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
2 sitesGreece
Study dates
20 Oct 2016to 10 Jan 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Treatment initiation planned less than 1 week (7 days) after registration
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if theyhave been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior of starting study treatment
  • Women of childbearing potential and their partners, who are sexually active, must agree to the use of TWO highly effective forms of contraception in combination, throughout the period of taking study treatment and for at least 1-6 month (according to the treatment group) after last dose of study drug(s) (where applicable). Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of TWO highly effective forms of contraception in combination, throughout the period of taking study treatment and for 3- 6 months (according tot he treatment group) after last dose of study drug(s) (where applicable).

Who cannot join

  • 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.
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  • Treatment with CYP3A4 inhibitors as well as inducers, unless discontinued 7 days prior to randomization
  • Any of the following within 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis
  • 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
  • Active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.
  • History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan
  • Other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial
  • Known history of positive tests for human immunodeficiency virus (HIV) infection, hepatitis A or C virus, acute or chronic active hepatitis B infection
  • History of severe tumour bleeding or bleeding disorders
  • No blood transfusion within the 28 days prior to study
  • Poorly controlled anti-coagulation therapy (INR3.0 on coumadin or heparin compounds)
  • Palliative radiation therapy within 4 weeks prior to registration
  • Pregnancy or men or women of reproductive age not agreeing to use contraceptive measures

Trial locations and contacts

2 sites in 1 country.

Greece2 sites

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

    Athens, 12462

  • Euromedica General Clinic of Thessaloniki

    Thessaloniki, Thessaloniki, 54645

Other trials in Greece

About this study

Official title: Phase II(Window) Preoperative Study of Olaparib With Cisplatin or With Durvalumab (MEDI4736) or Alone or no Treatment in Patients With Histologically Proven Squamous Cell Carcinoma of the Head and Neck Who Are Candidates for Surgery.

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.

Read the detailed description

OPHELIA is a window-of-opportunity phase II study randomized between combination with durvalumab and olaparib, cisplatin and olaparib, monotherapy with olaparib or no treatment, before starting standard treatment.

Although patients will be randomized between the 4 arms, no formal comparison between the 4 arms will be performed.Patients allocated to the olaparib monotherapy arm will serve as a proof-of-concept to interpret the mechanism of action of olaparib. Patients allocated in the "no treatment" group will be used as control.

The primary endpoint will be the change in the tumour Ki-67 before and after treatment with the combination of olaparib + durvalumab or olaparib + cisplatin or olaparib monotherapy. Secondary endpoints will be early tumour response by RECIST criteria, pathologic complete response rate, tolerability to treatment and surgical complications rate, and optionally, metabolic response assessed by FDG-PET/CT scan. Translational correlates will be tested in tumour tissue, plasma and germline DNA.

All the endpoints will be analyzed by an "as treated analysis" since the trial does not include a formal comparison of the treatment arms.

Administration of olaparib monotherapy has been associated with reports of the following laboratory findings and/or clinical diagnoses, generally of mild or moderate severity (CTCAE Grade 1 or 2) and generally not requiring treatment discontinuation.

Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OlaparibDrug

    Also called Lynparza

    50/25 mg BD split x 5 days

  • CisplatinDrug

    Also called Platamine

    60 mg/m^2 d1-d5

  • OlaparibDrug

    Also called Lynparza

    300 mg BD x 21-28 days.

  • DurvalumabDrug

    Also called Imfinzi

    1500 mg d1

Study groups in NCT02882308
Study groupRoleWhat they receive
Monotherapy with olaparibExperimentalPatients 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.
Receives: Drug: Olaparib
Combination of cisplatin and olaparibExperimentalPatients 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.
Receives: Drug: Olaparib; Drug: Cisplatin
No treatment armNo interventionPatients 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 olaparibExperimentalPatients 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.
Receives: Drug: Olaparib; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (23)

  1. Objective response rate according to RECIST 1.1 criteria

    Measured: Imaging studies will be performed at baseline and on week 4

  2. Pathologic complete response rate

    Measured: On week 4 only for operable patients

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

    Measured: At baseline, on week 4

  4. Number of participants with tolerability to the treatment.

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

  5. Surgical complication rate

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

  6. Mutations in genes associated with DNA repair

    Measured: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

  7. Expression of tissue biomarker: PARP1

    Measured: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

  8. Expression of tissue biomarker: BRACA1,2

    Measured: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

  9. Expression of tissue biomarker: ERCC1

    Measured: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

  10. Expression of tissue biomarker: PDL-1

    Measured: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

  11. Expression of tissue biomarker: TILs

    Measured: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

  12. Plasma methylation biomarker: PARP1 methylation in plasma cell-free DNA

    Measured: At baseline, a day before surgery and 90 days after surgery

  13. Plasma methylation biomarker: BRCA1,2 methylation in plasma cell-free DNA

    Measured: At baseline, a day before surgery and 90 days after surgery

  14. Plasma methylation biomarker: ERCC1 methylation in plasma cell-free DNA

    Measured: At baseline, a day before surgery and 90 days after surgery

  15. Plasma methylation biomarker: RAD51C methylation in plasma cell-free DNA

    Measured: At baseline, a day before surgery and 90 days after surgery

  16. Single-nucleotide polymorphisms: PARP-1 Val762Ala

    Measured: Sample will be collected once at baseline

  17. Single-nucleotide polymorphisms: ERCC1 Asn118Asn (C/T)

    Measured: Sample will be collected once at baseline

  18. Single-nucleotide polymorphisms:ERCC2 Lys751Gln (T/G)

    Measured: Sample will be collected once at baseline

  19. Single-nucleotide polymorphisms: GSTP1 Ile105Val (A/G)

    Measured: Sample will be collected once at baseline

  20. Single-nucleotide polymorphisms: XPD Lys751Gln (A/C, C/C)

    Measured: Sample will be collected once at baseline

  21. Single-nucleotide polymorphisms: XRCC1 Arg399Gln (G/A)

    Measured: Sample will be collected once at baseline

  22. Circulating tumor cells (CTCs) evaluated for DNA repair biomarkers

    Measured: At baseline, a day before surgery and 90 days after surgery

  23. Circulating tumor cells (CTCs) evaluated for PD-L1

    Measured: At baseline, a day before surgery and 90 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2016 (estimated)
  2. Study start20 Oct 2016
  3. Primary completionDec 2019
  4. Study completion10 Jan 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02882308
Sponsor's protocol ID
HE5A/15
Other IDs
2015-005268-41, 2015
Acronym
OPHELIA
Status last verified
Feb 2020
First submitted
20 Jul 2016
Last updated
7 Feb 2020
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 33714009

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Olaparib, Cisplatin and Durvalumab in people with Squamous Cell Carcinoma of the Head and Neck, run by Hellenic Cooperative Oncology Group at 2 sites in Greece.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: At baseline and at the day of the surgery or 2nd biopsy (at days 23-29 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02882308, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2020.

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