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Head and Neck Squamous Cell CarcinomaPhase 1/2NCT01711541

Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer

A Phase 1/2 study testing Carboplatin, Cisplatin and Fluorouracil in people with Head and Neck Squamous Cell Carcinoma and Stage IVA Oropharyngeal Carcinoma AJCC v7, run by National Cancer Institute (NCI) at 5 sites in United States.

Completed

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

Official record
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Trial summary

This partially randomized phase I/II trial studies the side effects and best dose of veliparib when given together with combination chemotherapy and to see how well they work in treating patients with stage IV head and neck cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carboplatin, Cisplatin and Fluorouracil
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
5 sitesUnited States
Study dates
22 Oct 2012to 15 May 2023
Phase
Phase 1/2
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

  • PHASE I:
  • Patients who are treatment naïve, high risk, stage IVa/IVb (all other sites) and histologically proven squamous cell carcinoma of the head and neck (SCCHN) with no definitive evidence of metastatic disease, excluding patients with oropharynx human papillomavirus (HPV)-positive tumors; in summary, those patients eligible are newly diagnosed and treatment naive:
  • Stage IVa-b squamous cell carcinoma other than oropharyngeal cancer (OPC), or
  • Oropharyngeal cancer (OPC) HPV-negative, stage IVa-b
  • PHASE II:
  • Patients who are treatment naïve, high risk, stage IVa/IVb (all other sites) histologically proven SCCHN with no definitive evidence of metastatic disease; in summary, those patients eligible are:
Show all 31Show fewer
  • Stage IVa-b SCCHN other than OPC, or
  • OPC, HPV-negative, IVa-b, or
  • OPC, HPV positive, with greater than 10 pack-year smoking history and N2b-N3 disease
  • PHASE I AND II:
  • Patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria; i.e., patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan magnetic resonance imaging (MRI), or calipers by clinical exam
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients must be able to swallow the drug
  • Ability to understand and the willingness to sign a written informed consent document
  • Leukocytes >= 3,000/mm^3
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Total bilirubin =< 1.5 institutional upper limit of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x institutional ULN as calculated by Cockcroft-Gault
  • Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above ULN as calculated by Cockcroft-Gault
  • Patients who are receiving any other investigational agents are not eligible
  • Patients with active seizure or a history of seizure are not eligible
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or other agents used in study, including Cremophor, carboplatin, paclitaxel, cisplatin, 5-fluorouracil, hydroxyurea, or any compounds of similar chemical or biologic composition are not eligible
  • Patients with impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of ABT-888 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) are not eligible to participate in this study
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible to participate in the study
  • Pregnant women are not eligible to participate in this study; NOTE: women of child bearing potential must have a negative serum or urine pregnancy test within 7 days prior to treatment
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately;
  • Breastfeeding should be discontinued if the mother is treated with ABT-888
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are not eligible
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent are not eligible to participate in this study; topical or inhaled corticosteroids are allowed
  • Patients with other malignancies within the past 2 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin or surgically treated early stage solid tumors are ineligible to participate in this study

Who cannot join

None listed.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Carboplatin-Paclitaxel Induction Chemotherapy and ABT-888 (Veliparib) - a Phase 1/Randomized Phase 2 Study in Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

This partially randomized phase I/II trial studies the side effects and best dose of veliparib when given together with combination chemotherapy and to see how well they work in treating patients with stage IV head and neck cancer. Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective when given with or without veliparib in treating head and neck cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose (MTD), recommended phase II dose, dose limiting toxicity (DLT), and safety of ABT-888 (veliparib) with carboplatin and paclitaxel induction chemotherapy in locoregionally advanced head and neck (LAHNC) patients. (Phase I) II. Compare magnitude of tumor shrinkage (response) following 2 cycles of induction chemotherapy with and without ABT-888 in LAHNC. (Phase II)

SECONDARY OBJECTIVES:

  1. Compare progression-free (PFS), disease-specific (DSS), and overall survival (OS) in subjects treated with or without ABT-888. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a phase II study.

PHASE I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7, paclitaxel intravenously (IV) over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive veliparib, paclitaxel, and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.

ARM II: Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.

CONCOMITANT CHEMORADIOTHERAPY: Patients are assigned to 1 of 2 regimens of concomitant chemoradiotherapy based on the guidelines of the institution where they are being treated.

OPTION I (CONCOMITANT CHEMORADIATION WITH CISPLATIN): Patients receive cisplatin IV on days 1 and 22 and undergo radiation therapy 5 days per week for 6 weeks. Treatment repeats every 2 weeks for 5 courses.

OPTION II (CONCOMITANT CHEMORADIATION WITH TFHX): Patients receive hydroxyurea PO every 12 hours on days 1-5 for up to 11 doses, fluorouracil IV over 120 hours on days 1-5, paclitaxel IV on day 1, and undergo radiation therapy BID on days 1-5. Treatment repeats every 2 weeks for 5 courses.

After completion of study treatment, patients are followed up at 2 weeks, 1, 3, 6, 12, 18, 24, 30, 36, 48, and 60 months. Patients who progress will be followed up every 6 months through year 5.

Being tested
Carboplatin, Cisplatin, Fluorouracil, Hydroxyurea, Laboratory Biomarker Analysis
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Oropharyngeal Neoplasms

What participants receive

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

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • HydroxyureaDrug

    Also called Droxia, Hydrea, Hydroxycarbamide, Litalir

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Placebo AdministrationOther

    Given PO

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo radiation therapy

  • VeliparibDrug

    Also called ABT-888, PARP-1 inhibitor ABT-888

    Given PO

Study groups in NCT01711541
Study groupRoleWhat they receive
Arm I (veliparib, combination chemotherapy)ExperimentalPatients receive veliparib PO BID on days 1-7, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.
Receives: Drug: Carboplatin; Drug: Cisplatin; Drug: Fluorouracil; Drug: Hydroxyurea; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Radiation: Radiation Therapy; Drug: Veliparib
Arm II (placebo, combination chemotherapy)ExperimentalPatients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.
Receives: Drug: Carboplatin; Drug: Cisplatin; Drug: Fluorouracil; Drug: Hydroxyurea; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Placebo Administration; Radiation: Radiation Therapy

What is being measured

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

  1. Dose Limiting Toxicity (Phase I)

    Dose Limiting Toxicity (DLTs) will be assessed during the first cycle of induction chemotherapy.

    The following events are considered DLTs: Grade 4 neutropenia (ANC < 500) lasting more than 14 days, Febrile neutropenia, Grade 4 thrombocytopenia, dose delay of greater than 3 weeks due to failure to recover counts, treatment-related grade 3 or grade 4 non-hematological toxicity (excluding alopecia, fatigue, hypersensitivity reaction, nausea, vomiting, constipation, diarrhea, hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, and grade 3 hypertension), a dose delay of greater than 3 weeks for non-hematological toxicity despite replacement of electrolytes, maximum treatment for diarrhea, nausea, vomiting, and hypertension, any drug-related death.

    The number of patients reporting a DLT are reported below. The maximum tolerated dose (MTD) will be determined as the highest dose where 1 or fewer out of 6 patients reports a DLT.

    Measured: Up to 3 weeks

  2. Relative Change in Tumor Size as Measured by RECIST (Phase II)

    Treatment arms will be compared using the nonparametric Wilcoxon rank-sum test.

    Measured: From baseline to 6 weeks

Secondary outcomes (6)

  1. Toxicity (Phase I and Phase II)

    Adverse Events were collected each cycle during treatment and follow-up according to the CTCAE v4.0 guidelines. The worst graded adverse event was determined for each patient. Below is a table of the number of patients that reported a Grade 3 or Grade 4 or Grade 5 as their worst reported event.

    Measured: upt to 5 years

  2. PFS (Phase II)

    Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.

    Measured: Up to 5 years

  3. Disease-free Survival (Phase II)

    Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.

    Measured: Up to 5 years

  4. Time to Local or Distant Progression (Phase II)

    Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.

    Measured: Up to 5 years

  5. DSS (Phase II)

    Summarized using cumulative incidence, and will be compared between groups using Gray's test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.

    Measured: Up to 5 years

  6. OS (Phase II)

    Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.

    Measured: Up to 5 years

Timeline

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

  1. First posted22 Oct 2012 (estimated)
  2. Study start22 Oct 2012
  3. Primary completion15 Feb 2018
  4. Study completion15 May 2023

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01711541
Sponsor's protocol ID
NCI-2012-02009
Other IDs
NCI-2012-02009, A091101, A091101, A091101, N01CM62201, U10CA180821, U10CA031946
Status last verified
Jun 2023
First submitted
18 Oct 2012
Last updated
7 Jun 2023
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carboplatin, Cisplatin and Fluorouracil in people with Head and Neck Squamous Cell Carcinoma and Stage IVA Oropharyngeal Carcinoma AJCC v7, run by National Cancer Institute (NCI) at 5 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 31 inclusion and 0 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 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 combined 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.

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?

Yes. Results are posted in the registry (first posted 5 Jun 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?

Dose Limiting Toxicity (Phase I) (time frame: Up to 3 weeks). 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?

On the ClinicalTrials.gov record for NCT01711541.

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 Jun 2023.

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