Squamous Cell Carcinoma of the Head and NeckPhase 1NCT01758731
Study of Olaparib With Radiation Therapy and Cetuximab in Advanced Head and Neck Cancer With Heavy Smoking History
A Phase 1 study testing Olaparib, Cetuximab and Radiation Therapy in people with Squamous Cell Carcinoma of the Head and Neck, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This is a research study that plans to learn more about the safety and tolerability of an investigational drug called Olaparib, in combination with radiation therapy and cetuximab. 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, Cetuximab and Radiation Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Oct 2012to 31 Oct 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 fully informed consent prior to any study specific procedures.
- Patients must be > 18 years of age.
- Histologically or cytologically confirmed (from the primary lesion and/or regional lymph nodes) squamous cell carcinoma of the oropharynx, hypopharynx, or larynx that has not been previously treated or resected
- Stage IV A or stage IV B disease prior to induction chemotherapy with no proven hematogenous metastatic disease (includes T4aN0-1M0, T1-4aN2M0, T4b, any N, M0 or any T, N3M0)
- History of ≥ 10 pack-years of smoking cigarettes.
- Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
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- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- White blood cells (WBC) > 3x109/L
- Platelet count ≥ 100 x 109/L
- Total bilirubin ≤ 1.5 x institutional upper limit of normal
- Aspartate Aminotransferase(AST) (SGOT)/Alanine Aminotransferase (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 upper limit of normal (ULN)
- Creatinine clearance (CCr) ≥ 50 ml/min within 2 weeks prior to registration as determined by 24-hour collection or estimated by Cockcroft-Gault formula:
- CCr male = [(140 - age) x (wt in kg)]/ [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male)
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (see Appendix F)
- Patients must have a life expectancy ≥ 16 weeks.
- Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1
- Postmenopausal is defined as:
- Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,
- luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50,
- radiation-induced oophorectomy with last menses >1 year ago,
- chemotherapy-induced menopause with >1 year interval since last menses,
- or surgical sterilisation (bilateral oophorectomy or hysterectomy).
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- At least one lesion prior to induction chemotherapy, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT), magnetic resonance imaging (MRI) or clinical examination (for instance, palpable lymph node in neck) and which is suitable for accurate repeated measurements.
- Patients with measurable disease prior to induction Docetaxel, Cisplatin and 5-fluorouracil (TPF) chemotherapy who obtain a complete clinical response prior to assignment to protocol therapy (RT + C225 + Olaparib) are still eligible for enrollment.
- If formalin fixed, paraffin embedded tumor sample from biopsy exists, it should be available for testing. For inclusion in genetic research (analysis of biologic marker expression), patients must fulfill the following criterion:
- Provision of informed consent for genetic (biomarker) research (If a patient declines to participate in the research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent to that part.)
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Previous enrollment (or assignment) in the present study
- Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used)
- Any previous treatment with a PARP inhibitor, including olaparib.
- Patients with second primary 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.
- Patients receiving any systemic chemotherapy or targeted agents for treatment of the current HNSCC
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- Patients receiving any prior radiation therapy to the head or neck.
- Patients receiving the following classes of inhibitors of Cytochrome P450 3A4 (see Section 5.4.2 for guidelines and wash out periods).
- Azole antifungals
- Macrolide antibiotics
- Protease inhibitors
- Toxicities > Common Toxicity Criteria for Adverse Effects (CTCAE) grade 2 caused by previous cancer therapy.
- Patients with metastatic disease (only Stage IVA-B patients permitted)
- Major surgery within 2 weeks 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. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. Evidence of severe or uncontrolled systemic disease or any concurrent condition which, in the investigator's opinion, makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
- Patients unable to swallow orally administered medication at treatment initiation and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
- Breast feeding women
- Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
- Patients with known active hepatic disease (i.e., Hepatitis B or C).
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product. Patients with known hypersensitivity to C225 or any of the excipients of the product.
- Patients with uncontrolled seizures.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Denver, Colorado, 80045
About this study
Official title: Phase I Trial of Olaparib (AZD2281) in Combination With C225 and Radiation Therapy in Patients With Locally Advanced, Stage IVA-B Squamous Cell Carcinomas of the Head/Neck With Heavy Smoking Histories
This is a research study that plans to learn more about the safety and tolerability of an investigational drug called Olaparib, in combination with radiation therapy and cetuximab.
Hypothesis: Intensity modulated radiotherapy with concurrent C225 and Olaparib represents a feasible, biologically-based alternative to standard chemoradiation, with acceptable toxicity, for treatment of locally-advanced HNSCC in patients having a ≥ 10 pack-year smoking history.
Read the detailed description
Outcomes for heavy smokers with locally-advanced head and neck squamous cell cancer (HNSCC) treated with standard chemoradiation have been traditionally poor, suggesting a critical need for translation of novel biologically-based targeted approaches into clinical practice. In clinical trials, the Poly(ADP-ribose) polymerase-1 (PARP1) inhibitor Olaparib has been combined with other systemic agents, including paclitaxel, irinotecan, carboplatin and gemcitabine, in the treatment of patients with various solid tumors. Pre-clinical models have shown cooperative effects of combining PARP inhibition with radiation. A combined modality approach utilizing RT in combination with C225 and Olaparib after induction chemotherapy represents a rational, targeted approach for investigation in locally-advanced HNSCC patients.
- Keywords
- Stage IVA-B Squamous Cell Carcinomas, Head and Neck Cancer, Heavy drinking, Smoking
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
Also called AZD2281
Olaparib PO (25, 50, 100 or 200 mg bid) in combination with RT and C225. BID, beginning three days prior to first C225 infusion and discontinued after RT completed.
CetuximabDrug
Also called Erbitux
Pre-RT cetuximab (C225), 400 mg/m²IV and weekly C225, 250 mg/m2 IV in during RT.
Radiation TherapyRadiation
RT to a total dose of 69.3 Gy (primary tumor and involved lymph nodes) in 33 fractions over 6 and 1/2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Olaparib with C225 and Radiation Therapy | Experimental | Patients will begin taking Olaparib at the assigned dose three days prior to their first Cetuximab infusion. Patients will receive an initial dose of Cetuximab, 400 mg/m², intravenously over 120 minutes on Day 1. The initial dose of C225 will precede the start of radiation by 5-7 days. All patients will receive RT to a total dose of 69.3 Gy in 33 fractions over 6½ weeks. Weekly C225 will be administered at 250 mg/m2 in combination with daily RT. Patients will be assigned to receive Olaparib (25, 50, 100 or 200 mg bid) in combination with RT and C225. Olaparib will be taken twice daily, beginning three days prior to first scheduled C225 infusion. A further dose level of 300mg or 400mg may be considered should the 200mg Olaparib dose be well tolerated in this C225/RT combination schedule. Receives: Drug: Olaparib; Drug: Cetuximab; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Olaparib
Maximum tolerated dose (MTD) of Olaparib to be used for Phase II clinical testing.
Measured: 10 weeks from the start of protocol therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2013 (estimated)
- Study start22 Oct 2012
- Primary completion5 Dec 2016
- Study completion31 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Squamous Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Raben, M.D, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01758731
- Sponsor's protocol ID
- 11-1658.cc
- Status last verified
- Sep 2019
- First submitted
- 26 Dec 2012
- Last updated
- 23 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Olaparib (AZD2281) in Combination With C225 and Radiation Therapy in Patients With Locally Advanced, Stage IVA-B Squamous Cell Carcinomas of the Head/Neck With Heavy Smoking Histories
- ClinicalTrials.gov ID
- NCT01758731
- Acronym / sponsor ID
- 11-1658.cc
- Keywords
- Stage IVA-B Squamous Cell Carcinomas, Head and Neck Cancer, Heavy drinking, Smoking
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 22 Oct 2012 (actual)
- Primary completion
- 5 Dec 2016 (actual)
- Study completion
- 31 Oct 2018 (actual)
- First posted
- 1 Jan 2013 (estimated)
- Results
- Posted 23 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a research study that plans to learn more about the safety and tolerability of an investigational drug called Olaparib, in combination with radiation therapy and cetuximab.
Hypothesis: Intensity modulated radiotherapy with concurrent C225 and Olaparib represents a feasible, biologically-based alternative to standard chemoradiation, with acceptable toxicity, for treatment of locally-advanced HNSCC in patients having a ≥ 10 pack-year smoking history.
Detailed description
Outcomes for heavy smokers with locally-advanced head and neck squamous cell cancer (HNSCC) treated with standard chemoradiation have been traditionally poor, suggesting a critical need for translation of novel biologically-based targeted approaches into clinical practice. In clinical trials, the Poly(ADP-ribose) polymerase-1 (PARP1) inhibitor Olaparib has been combined with other systemic agents, including paclitaxel, irinotecan, carboplatin and gemcitabine, in the treatment of patients with various solid tumors. Pre-clinical models have shown cooperative effects of combining PARP inhibition with radiation. A combined modality approach utilizing RT in combination with C225 and Olaparib after induction chemotherapy represents a rational, targeted approach for investigation in locally-advanced HNSCC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olaparib with C225 and Radiation Therapy | Experimental | Drug: Olaparib, Drug: Cetuximab, Radiation: Radiation TherapyPatients will begin taking Olaparib at the assigned dose three days prior to their first Cetuximab infusion. Patients will receive an initial dose of Cetuximab, 400 mg/m², intravenously over 120 minutes on Day 1. The initial dose of C225 will precede the start of radiation by 5-7 days. All patients will receive RT to a total dose of 69.3 Gy in 33 fractions over 6½ weeks. Weekly C225 will be administered at 250 mg/m2 in combination with daily RT. Patients will be assigned to receive Olaparib (25, 50, 100 or 200 mg bid) in combination with RT and C225. Olaparib will be taken twice daily, beginning three days prior to first scheduled C225 infusion. A further dose level of 300mg or 400mg may be considered should the 200mg Olaparib dose be well tolerated in this C225/RT combination schedule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Provision of fully informed consent prior to any study specific procedures.
- Patients must be > 18 years of age.
- Histologically or cytologically confirmed (from the primary lesion and/or regional lymph nodes) squamous cell carcinoma of the oropharynx, hypopharynx, or larynx that has not been previously treated or resected
- Stage IV A or stage IV B disease prior to induction chemotherapy with no proven hematogenous metastatic disease (includes T4aN0-1M0, T1-4aN2M0, T4b, any N, M0 or any T, N3M0)
- History of ≥ 10 pack-years of smoking cigarettes.
Key exclusion criteria (21 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Previous enrollment (or assignment) in the present study
- Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used)
- Any previous treatment with a PARP inhibitor, including olaparib.
- Patients with second primary 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.
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: AZD2281Olaparib PO (25, 50, 100 or 200 mg bid) in combination with RT and C225. BID, beginning three days prior to first C225 infusion and discontinued after RT completed. | Drug | Olaparib with C225 and Radiation Therapy |
| CetuximabAlso: ErbituxPre-RT cetuximab (C225), 400 mg/m²IV and weekly C225, 250 mg/m2 IV in during RT. | Drug | Olaparib with C225 and Radiation Therapy |
| Radiation TherapyRT to a total dose of 69.3 Gy (primary tumor and involved lymph nodes) in 33 fractions over 6 and 1/2 weeks | Radiation | Olaparib with C225 and Radiation Therapy |
Primary outcome
Maximum Tolerated Dose (MTD) of Olaparib
Time frame: 10 weeks from the start of protocol therapy
Maximum tolerated dose (MTD) of Olaparib to be used for Phase II clinical testing.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
David Raben, M.D principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Olaparib, Cetuximab and Radiation Therapy in people with Squamous Cell Carcinoma of the Head and Neck, run by University of Colorado, Denver at 1 site in United States.
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 29 inclusion and 21 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 23 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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?
Yes. Results are posted in the registry (first posted 23 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) of Olaparib (time frame: 10 weeks from the start of protocol therapy). 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 23 Sep 2019.