Know Cancer

or
forgot password

TPF 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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Human Papilloma Virus Infection, Salivary Gland Squamous Cell Carcinoma, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Salivary Gland Cancer, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Salivary Gland Cancer, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Tongue Cancer

Thank you

Trial Information

TPF 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


PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD), recommended phase II dose, dose limiting
toxicity (DLT), and safety of ABT-888 (veliparib) with cisplatin, 5FU (fluorouracil), and a
taxane (TPF) 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 consisting of TPF with and without ABT-888 in LAHNC. (Phase II)

SECONDARY OBJECTIVES:

I. 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, docetaxel
intravenously (IV) over 60 minutes on day 2, cisplatin IV over 60 minutes on day 2, and
fluorouracil IV continuously over 120 hours on days 2-6. 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, docetaxel, cisplatin, and fluorouracil as in Phase I.
Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or
unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.

ARM II: Patients receive placebo PO BID on days 1-7. Patients also receive docetaxel,
cisplatin, and fluorouracil as in Phase I. Treatment repeats every 3 weeks for 2 courses in
the absence of disease progression or unacceptable toxicity. Patients then continue on to
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.

CONCOMITANT CHEMORADIATION WITH CISPLATIN: Patients receive cisplatin IV on days 1 and 22 or
2 and 23 and undergo radiation therapy five days a week for 6 weeks.

CONCOMITANT CHEMORADIATION WITH TFHX: Patients receive hydroxyurea PO every 12 hours on days
1-6 (11 doses), fluorouracil IV over 120 hours on days 2-6, paclitaxel IV on day 2, and
undergo radiation therapy BID on days 2-6. Treatment repeats every 2 weeks for 5 courses.

After completion of study treatment, patients are followed up at 2 weeks, 1 and 3 months,
every 3 months for 2 years, every 6 months for 1 year, and then annually for 2 years.


Inclusion Criteria:



- PHASE I:

- Patients who are treatment naive, high risk, stage III (hypopharynx) or patients who
are treatment naive, 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 papilloma
virus (HPV)-positive tumors; in summary, those patients eligible are newly diagnosed
and treatment naive:

- Stage III (hypopharynx), OR

- Stage IVa-b squamous cell carcinoma other than oropharyngeal cancer (OPC), OR

- OPC HPV-negative, stage IVa-b

- PHASE II:

- Patients who are treatment naive, high risk, stage III (hypopharynx) or patients who
are treatment naive, high risk, stage IVa/IVb (all other sites) and histologically
proven SCCHN with no definitive evidence of metastatic disease; in summary, those
patients eligible are:

- Stage III (hypopharynx), OR

- Stage IVa-b SCCHN other than oropharyngeal cancer (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 =< 2

- 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 =< institutional upper limit of normal (ULN)

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 X
institutional ULN

- Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above
ULN

- 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, docetaxel, 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 registration; ABT-888 is a poly adenosine diphosphate ribose (ADP) ribose
polymerase (PARP) inhibitor with the potential for teratogenic or abortifacient
effects;

- 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;

- Because there is an unknown but potential risk for adverse events in nursing
infants secondary to treatment of the mother with ABT-888, breastfeeding should
be discontinued if the mother is treated with ABT-888; these potential risks may
also apply to other agents used in this study

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are not eligible because of the potential for pharmacokinetic interactions
with ABT-888

- 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

MTD of veliparib, graded according to the Common Terminology Criteria for Adverse Events (NCI CTCAE) (Phase I)

Outcome Time Frame:

Up to 3 weeks

Safety Issue:

Yes

Principal Investigator

Jonas De Souza

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02009

NCT ID:

NCT01711541

Start Date:

October 2012

Completion Date:

Related Keywords:

  • Human Papilloma Virus Infection
  • Salivary Gland Squamous Cell Carcinoma
  • Stage III Squamous Cell Carcinoma of the Hypopharynx
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • Stage IVA Salivary Gland Cancer
  • Stage IVA Squamous Cell Carcinoma of the Larynx
  • Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVA Squamous Cell Carcinoma of the Oropharynx
  • Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVA Verrucous Carcinoma of the Larynx
  • Stage IVA Verrucous Carcinoma of the Oral Cavity
  • Stage IVB Salivary Gland Cancer
  • Stage IVB Squamous Cell Carcinoma of the Larynx
  • Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVB Squamous Cell Carcinoma of the Oropharynx
  • Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVB Verrucous Carcinoma of the Larynx
  • Stage IVB Verrucous Carcinoma of the Oral Cavity
  • Tongue Cancer
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms
  • Laryngeal Diseases
  • Papilloma
  • Virus Diseases
  • Tongue Neoplasms
  • Carcinoma, Verrucous
  • Salivary Gland Neoplasms
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Warts
  • Paranasal Sinus Neoplasms
  • Papillomavirus Infections
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Cancer and Leukemia Group BChicago, Illinois  60606