Squamous Cell Carcinoma of the Head and NeckPhase 1NCT02686008
Pharmacodynamic Study to Assess the Anti-proliferative Activity of the PARP Inhibitor Olaparib in Patients With HPV Positive and HPV Negative HNSCC
A Phase 1 study testing Olaparib in people with Squamous Cell Carcinoma of the Head and Neck, run by Yale University.
Trial summary
This is an open label pilot study evaluating the pharmacodynamics and safety of single agent olaparib administered at 300mg bid (twice a day) for 14 days orally in patients with human papillomavirus (HPV) -positive and human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Olaparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2018to Jul 2019
- Phase
- Phase 1
- 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
- Histologically confirmed HNSCC with surgically resectable disease
- No prior chemotherapy or radiation therapy as treatment for the observed HNSCC
- Patients must provide written informed consent
- Age >=18 years of age
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of <2
- Normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
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- Hemoglobin >= 10 g/dL and no blood transfusions in the 28 days prior to entry/randomization
- Absolute neutrophil count >=1.5 x 10^9/L
- No features suggesting of MDS/AML on peripheral blood smear
- White blood cells > 3 x 10^9/L
- Platelet count >= 100 x 10^9/L
- Total bilirubin <= 1.5 x institutional upper limit of normal (ULN)
- AST (SGOT)/ALT (SGPT) < 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be < 5x ULN
- Serum creatinine <= 1.5 x institutional ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of the study participation and must have negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial
- Must be abler to understand and sign a written informed consent document
Who cannot join
- Patients with known brain metastases. Patients may have received WBRT within 14 days or focal radiation within 1 week of cycle 1, day 1. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment
- Women must not be pregnant or breastfeeding
- Patients with known hypersensitivity to olaparib or any of the excipients of the product
- Patients receiving any other investigational agents within 4 weeks of starting the study
- Involvement in the planning and/or conduct of the study
- Any previous treatment with a PARP inhibitor, including olaparib
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- Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin, and nelfinavir
- Persistent toxicities (>=CTCAE grade 2)
- Resting ECG with QTC >470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
- Blood transfusions within 1 month prior to study start
- Patients with myelodysplastic syndrome/acute myeloid leukemia
- Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery
- Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
- Unable to swallow oral medication
- Immunocompromised patients, e.g., patients who are known to be serologically positive for HIV and are receiving antiviral therapy
- Known active hepatic disease
- Uncontrolled seizures
- Previous cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for 5 years
- Currently on warfarin(subcutaneous heparin is permitted)
About this study
Official title: A Pilot Pharmacodynamic Study to Assess the Anti-proliferative Activity a of the Poly ADP Ribose Polymerase (PARP) Inhibitor Olaparib in Patients With Human Papilloma Virus (HPV) Positive and Human Papilloma Virus (HPV) Negative Head and Neck Squamous Cell Carcinoma (HNSCC)
This is an open label pilot study evaluating the pharmacodynamics and safety of single agent olaparib administered at 300mg bid (twice a day) for 14 days orally in patients with human papillomavirus (HPV) -positive and human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC)
- Being tested
- Olaparib
- 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
Patients will receive olaparib administered at 300 mg bid x 14 days orally
| Study group | Role | What they receive |
|---|---|---|
| HPV negative tumors | Experimental | 10 patients with HPV negative tumors: Non-oropharyngeal tumors or p16 negative and HPV negative oropharyngeal tumors Receives: Drug: Olaparib |
| HPV positive tumors | Experimental | 10 patients with HPV positive tumors: p16 positive and HPV positive tumors Receives: Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Level of IHC-Ki-67 expression
Tissue biopsy sections will be analyzed for proliferation (IHC-Ki-67) Ki-67 is a nuclear non-histone protein that is present at low levels in quiescent cells but is increased in proliferating cells. Thus, Ki-67 reactivity, defined as percent tumor cells staining positive as measured by immunohistochemical (IHC) staining, is a specific nuclear marker for cell proliferation.
Measured: Baseline and 14 days
Secondary outcomes (2)
Change in Tissue apoptosis
Tissue biopsy sections will be analyzed for apoptosis. For example using the IHC-cleaved caspase-3 assay.
Measured: Baseline and 14 days
Change in DNA repair pathways
Tissue biopsy sections will be analyzed to determine effect on DNA repair pathways (PARP activity). Specifically Poly(ADP-ribose) immunohistochemical staining of tissue biopsies will be performed and PAR intensity scored as 0 (no signal), 1 (weak), 2 (strong intensity in >50% of tumor cells).
Measured: Baseline and 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2016 (estimated)
- Study startJan 2018 (estimated)
- Primary completionJan 2019 (estimated)
- Study completionJul 2019 (estimated)
Why it stopped: The study was stopped due to lack of funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne Chiang, MD, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02686008
- Sponsor's protocol ID
- 1409014536
- Status last verified
- Jan 2020
- First submitted
- 24 Sep 2015
- Last updated
- 13 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Pharmacodynamic Study to Assess the Anti-proliferative Activity a of the Poly ADP Ribose Polymerase (PARP) Inhibitor Olaparib in Patients With Human Papilloma Virus (HPV) Positive and Human Papilloma Virus (HPV) Negative Head and Neck Squamous Cell Carcinoma (HNSCC)
- ClinicalTrials.gov ID
- NCT02686008
- Acronym / sponsor ID
- 1409014536
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was stopped due to lack of funding.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Jan 2018 (estimated)
- Primary completion
- Jan 2019 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 19 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label pilot study evaluating the pharmacodynamics and safety of single agent olaparib administered at 300mg bid (twice a day) for 14 days orally in patients with human papillomavirus (HPV) -positive and human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HPV negative tumors | Experimental | Drug: Olaparib10 patients with HPV negative tumors: Non-oropharyngeal tumors or p16 negative and HPV negative oropharyngeal tumors |
| HPV positive tumors | Experimental | Drug: Olaparib10 patients with HPV positive tumors: p16 positive and HPV positive tumors |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically confirmed HNSCC with surgically resectable disease
- No prior chemotherapy or radiation therapy as treatment for the observed HNSCC
- Patients must provide written informed consent
- Age >=18 years of age
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of <2
Key exclusion criteria (19 listed)
- Patients with known brain metastases. Patients may have received WBRT within 14 days or focal radiation within 1 week of cycle 1, day 1. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment
- Women must not be pregnant or breastfeeding
- Patients with known hypersensitivity to olaparib or any of the excipients of the product
- Patients receiving any other investigational agents within 4 weeks of starting the study
- Involvement in the planning and/or conduct of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlaparibAlso: LynparzaPatients will receive olaparib administered at 300 mg bid x 14 days orally | Drug | HPV negative tumors, HPV positive tumors |
Primary outcome
Change in Level of IHC-Ki-67 expression
Time frame: Baseline and 14 days
Tissue biopsy sections will be analyzed for proliferation (IHC-Ki-67) Ki-67 is a nuclear non-histone protein that is present at low levels in quiescent cells but is increased in proliferating cells. Thus, Ki-67 reactivity, defined as percent tumor cells staining positive as measured by immunohistochemical (IHC) staining, is a specific nuclear marker for cell proliferation.
2 secondary outcomes
Change in Tissue apoptosis
Time frame: Baseline and 14 days
Change in DNA repair pathways
Time frame: Baseline and 14 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne Chiang, MD, PhD principal investigator
Yale University
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Olaparib in people with Squamous Cell Carcinoma of the Head and Neck, run by Yale University.
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 16 inclusion and 19 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: withdrawn, as of the sponsor's last update on 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was withdrawn before enrolling participants, so there are no results.
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?
Change in Level of IHC-Ki-67 expression (time frame: Baseline and 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jan 2020.