Head and Neck CancerPhase 1NCT01721525
Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
A Phase 1 study testing Afatinib, Ribavirin, and weekly carboplatin/paclitaxel in people with Head and Neck Cancer and Squamous Cell Cancer, run by Memorial Sloan Kettering Cancer Center at 2 sites in United States.
Trial summary
This study seeks to develop a new induction chemotherapy regimen which is a combination of two pill drugs taken by mouth and two drugs given by vein. This is a phase I study, which means that the primary goal is to establish the recommended dose of an investigational drug when added to chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Squamous Cell Cancer
- What is being tested?
- Afatinib, Ribavirin, and weekly carboplatin/paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2012to 16 Oct 2017
- 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
- Department of Pathology at MSKCC confirmation of diagnosis of oropharynx squamous cell cancer, stage IVA/IVB, that is HPV associated.
- Evidence of HPV can be p16 immunohistochemistry and/or HPV in situ hybridization positive test result on tumor tissue, either at MSKCC or other CLIA-approved lab.
- Age ≥ 18 years of age
- Karnofsky Performance Status ≥ 80
- Adequate organ function, as follows:
- Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 X 109/L, platelets ≥ 160 X 109/L, hemoglobin ≥ 12 g/dL Hepatic: total bilirubin within normal limits (≤ 1.0 mg/dL); alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 X ULN (upper limit of normal) Renal: Serum creatinine ≤ 1.3 mg/dL. Patients with serum creatinine > 1.3 mg/dL may be eligible if creatinine clearance (CrCl) ≥ 55 mL/min based on the standard Cockroft and Gault formula.
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- Patients of childbearing potential must have a negative serum pregnancy test within 14 days of treatment. Patients must agree to use a reliable method of birth control during and for 6 months following the last dose of study drug.
- Ability to swallow oral medication.
- Expansion Cohort only: At least one unstained slide from pre-treatment diagnostic biopsy or fine needle aspirate must be available for correlative immunohistochemistry study.
Who cannot join
- Prior chemotherapy or radiation for tonsillar or base of tongue squamous cell cancer
- History of hemolytic anemia or thalassemia
- Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment.
- Current therapeutic anticoagulation with Coumadin (warfarin)
- Current or prior treatment with ribavirin
- Known active Hepatitis B or C
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- Any prior documented history of transient ischemic attack (TIA) or cerebrovascular accident (CVA)
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- Clinically significant peripheral vascular disease
- Inability to discontinue any of the following potent P-gp inhibitors (cyclosporine, erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital salt with quinidine, ritonavir, valspodar, verapamil) or inducers (St John's wort, rifampicin).
- Known pre-existing interstitial lung disease.
- Presence of poorly controlled gastrointestinal disorders that could affect the absorption of the trial drug (e.g. Crohn's disease, ulcerative colitis, malabsorption, or CTC grade ≥2 diarrhea of any etiology) based on treating physician assessment.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Memorial Sloan Kettering Cancer Center at Basking Ridge
Basking Ridge, New Jersey, 07939
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase I Study of Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
This study seeks to develop a new induction chemotherapy regimen which is a combination of two pill drugs taken by mouth and two drugs given by vein. This is a phase I study, which means that the primary goal is to establish the recommended dose of an investigational drug when added to chemotherapy. The researchers wish to evaluate the effects, good and bad, of the investigational drug.
- Conditions
- Head and Neck Cancer, Squamous Cell Cancer
- Being tested
- Afatinib, Ribavirin, and weekly carboplatin/paclitaxel
- Keywords
- BIBW2992 (AFATINIB), CARBOPLATIN, RIBAVIRIN-ICN (VIRAZOLE), TAXOL (PACLITAXEL), OROPHARYNX, HPV associated, 12-150
- Medical subject headings
- Head and Neck Neoplasms, Neoplasms, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Afatinib, Ribavirin, and weekly carboplatin/paclitaxelDrug
Also called During the Expansion Cohort (Part 2), there is a two week run in of afatinib +, ribavirin. The Expansion Cohort begins with a Run-In period of approximately, 14 days, in which patients receive only afatinib + ribavirin. On Day -14, (Start of the of the Run-In), patients begin afatinib once daily (at 40 mg/daily the dose
Patients will receive oral daily afatinib (days 1 - 21, per dose escalation scheme) plus daily oral ribavirin (days 1- 21) and paclitaxel (80 mg/m2 intravenously, days 1 and 8) + carboplatin (AUC 1.5 intravenously, days 1 and 8) of a 21-day cycle. Ribavirin will be administered according to standard weight-based dosing for this drug (1). Subjects ≤75 kg receive Ribavirin 400 mg PO qAM and 600 mg PO qPM (= 1000 mg/day). Subjects > 75 kg receive Ribavirin 600 mg PO BID (=1200 mg/day). During the Dose Escalation portion of the study (Part 1), research bloodwork for pharmacokinetics is performed on days 1 and 8 of Cycle 1 only.
| Study group | Role | What they receive |
|---|---|---|
| afatinib, ribavirin, and weekly carboplatin/paclitaxel | Experimental | This will be a single institution phase I study with an expansion cohort. Up to 2 dose levels of daily afatinib will be studied: 30 mg/day and 40 mg/day. The doses of ribavirin, carboplatin, and paclitaxel are fixed. A standard 3 + 3 phase I dose escalation design will be used. Receives: Drug: Afatinib, Ribavirin, and weekly carboplatin/paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
maximum tolerated dose (For Dose Escalation Portion of the study)
of daily oral afatinib administered with standard daily weight based ribavirin and intravenous carboplatin and paclitaxel, Up to 2 dose levels of daily afatinib will be studied: 30 mg/day and 40 mg/day. The doses of ribavirin, carboplatin, and paclitaxel are fixed. A standard 3 + 3 phase I dose escalation design will be used.
Measured: 1 year
expression of PTPN13 (For Expansion Cohort only)
To determine if a two week run-in with afatinib and ribavirin results in increased expression of PTPN13, as determined by IHC in pre and post treatment biopsies.
Measured: 1 year
Secondary outcomes (3)
safety and tolerability (toxicity)
Adverse events (AEs) will be assessed according to NCI common toxicity criteria (CTC) version 4.0. Dose Limiting Toxicity (DLT) include all toxicities of grade 3 or higher felt to be possibly, probably, or definitely related to study drug.
Measured: 1 year
objective response rate
Response and progression will be evaluated in this study using modified international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) (51). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
Measured: 1 year
pharmacokinetics
PK measurements will be collected from patients in the dose excalation cohort during the first cycle of therapy. The area under the curve (AUC0→∞), half-life (t½), and maximum concentration (Cmax) for afatinib will be determined by noncompartmental analysis.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2012 (estimated)
- Study startNov 2012
- Primary completion16 Oct 2017
- Study completion16 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network, Boehringer Ingelheim
- Responsible party
- Sponsor
- Investigators
- David Pfister, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01721525
- Sponsor's protocol ID
- 12-150
- Status last verified
- Oct 2017
- First submitted
- 1 Nov 2012
- Last updated
- 25 Oct 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
- ClinicalTrials.gov ID
- NCT01721525
- Acronym / sponsor ID
- 12-150
- Conditions
- Head and Neck Cancer, Squamous Cell Cancer
- Keywords
- BIBW2992 (AFATINIB), CARBOPLATIN, RIBAVIRIN-ICN (VIRAZOLE), TAXOL (PACLITAXEL), OROPHARYNX, HPV associated, 12-150
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network, Boehringer Ingelheim
- Study start
- Nov 2012 (actual)
- Primary completion
- 16 Oct 2017 (actual)
- Study completion
- 16 Oct 2017 (actual)
- First posted
- 5 Nov 2012 (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 study seeks to develop a new induction chemotherapy regimen which is a combination of two pill drugs taken by mouth and two drugs given by vein. This is a phase I study, which means that the primary goal is to establish the recommended dose of an investigational drug when added to chemotherapy. The researchers wish to evaluate the effects, good and bad, of the investigational drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| afatinib, ribavirin, and weekly carboplatin/paclitaxel | Experimental | Drug: Afatinib, Ribavirin, and weekly carboplatin/paclitaxelThis will be a single institution phase I study with an expansion cohort. Up to 2 dose levels of daily afatinib will be studied: 30 mg/day and 40 mg/day. The doses of ribavirin, carboplatin, and paclitaxel are fixed. A standard 3 + 3 phase I dose escalation design will be used. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Department of Pathology at MSKCC confirmation of diagnosis of oropharynx squamous cell cancer, stage IVA/IVB, that is HPV associated.
- Evidence of HPV can be p16 immunohistochemistry and/or HPV in situ hybridization positive test result on tumor tissue, either at MSKCC or other CLIA-approved lab.
- Age ≥ 18 years of age
- Karnofsky Performance Status ≥ 80
- Adequate organ function, as follows:
Key exclusion criteria (12 listed)
- Prior chemotherapy or radiation for tonsillar or base of tongue squamous cell cancer
- History of hemolytic anemia or thalassemia
- Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment.
- Current therapeutic anticoagulation with Coumadin (warfarin)
- Current or prior treatment with ribavirin
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 |
|---|---|---|
| Afatinib, Ribavirin, and weekly carboplatin/paclitaxelAlso: During the Expansion Cohort (Part 2), there is a two week run in of afatinib +, ribavirin. The Expansion Cohort begins with a Run-In period of approximately, 14 days, in which patients receive only afatinib + ribavirin. On Day -14, (Start of the of the Run-In), patients begin afatinib once daily (at 40 mg/daily the dosePatients will receive oral daily afatinib (days 1 - 21, per dose escalation scheme) plus daily oral ribavirin (days 1- 21) and paclitaxel (80 mg/m2 intravenously, days 1 and 8) + carboplatin (AUC 1.5 intravenously, days 1 and 8) of a 21-day cycle. Ribavirin will be administered according to standard weight-based dosing for this drug (1). Subjects ≤75 kg receive Ribavirin 400 mg PO qAM and 600 mg PO qPM (= 1000 mg/day). Subjects > 75 kg receive Ribavirin 600 mg PO BID (=1200 mg/day). During the Dose Escalation portion of the study (Part 1), research bloodwork for pharmacokinetics is performed on days 1 and 8 of Cycle 1 only. | Drug | afatinib, ribavirin, and weekly carboplatin/paclitaxel |
Primary outcome
maximum tolerated dose (For Dose Escalation Portion of the study)
Time frame: 1 year
of daily oral afatinib administered with standard daily weight based ribavirin and intravenous carboplatin and paclitaxel, Up to 2 dose levels of daily afatinib will be studied: 30 mg/day and 40 mg/day. The doses of ribavirin, carboplatin, and paclitaxel are fixed. A standard 3 + 3 phase I dose escalation design will be used.
expression of PTPN13 (For Expansion Cohort only)
Time frame: 1 year
To determine if a two week run-in with afatinib and ribavirin results in increased expression of PTPN13, as determined by IHC in pre and post treatment biopsies.
3 secondary outcomes
safety and tolerability (toxicity)
Time frame: 1 year
objective response rate
Time frame: 1 year
pharmacokinetics
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2017.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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 Pfister, MD principal investigator
Memorial Sloan Kettering Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Afatinib, Ribavirin, and weekly carboplatin/paclitaxel in people with Head and Neck Cancer and Squamous Cell Cancer, run by Memorial Sloan Kettering Cancer Center at 2 sites 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 9 inclusion and 12 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 25 Oct 2017. 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 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?
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?
maximum tolerated dose (For Dose Escalation Portion of the study) (time frame: 1 year). The study lists 2 primary outcomes in all. 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 25 Oct 2017; AzTrials last refreshed its copy on 8 Nov 2026.