Clinical Trial: NCT01711541 - My Cancer Genome

NCT01711541

Description:

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.

Related Conditions:

Head and Neck Squamous Cell Carcinoma
Oropharyngeal Carcinoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT01711541

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: NCI-2012-02009
SECONDARY ID: NCI-2012-02009
SECONDARY ID: A091101
SECONDARY ID: A091101
SECONDARY ID: A091101
SECONDARY ID: N01CM62201
SECONDARY ID: U10CA180821
SECONDARY ID: U10CA031946
NCT ID: NCT01711541

Conditions

Head and Neck Squamous Cell Carcinoma
Stage IVA Oropharyngeal Carcinoma AJCC v7
Stage IVB Oropharyngeal Carcinoma AJCC v7

Interventions

Drug	Synonyms	Arms
Carboplatin	Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo	Arm I (veliparib, combination chemotherapy)
Cisplatin	Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone''s Chloride, Peyrone''s Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin	Arm I (veliparib, combination chemotherapy)
Fluorouracil	5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757	Arm I (veliparib, combination chemotherapy)
Hydroxyurea	Droxia, Hydrea, Hydroxycarbamide, Litalir, Onco-Carbide, Oncocarbide, Oxeron, SQ 1089, SQ-1089, Syrea, WR 83799	Arm I (veliparib, combination chemotherapy)
Paclitaxel	Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat	Arm I (veliparib, combination chemotherapy)
Veliparib	ABT-888, PARP-1 inhibitor ABT-888	Arm I (veliparib, combination chemotherapy)

Purpose

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

      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, 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.

Trial Arms

Name	Type	Description	Interventions
Arm I (veliparib, combination chemotherapy)	Experimental	Patients 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.	Carboplatin Cisplatin Fluorouracil Hydroxyurea Paclitaxel Veliparib
Arm II (placebo, combination chemotherapy)	Experimental	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.	Carboplatin Cisplatin Fluorouracil Hydroxyurea Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  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:

               -  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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Dose Limiting Toxicity (Phase I)
Time Frame:	Up to 3 weeks
Safety Issue:
Description:	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.

Secondary Outcome Measures

Measure:	Toxicity (Phase I and Phase II)
Time Frame:	upt to 5 years
Safety Issue:
Description:	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.

Measure:	PFS (Phase II)
Time Frame:	Up to 5 years
Safety Issue:
Description:	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.

Measure:	Disease-free Survival (Phase II)
Time Frame:	Up to 5 years
Safety Issue:
Description:	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.

Measure:	Time to Local or Distant Progression (Phase II)
Time Frame:	Up to 5 years
Safety Issue:
Description:	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.

Measure:	DSS (Phase II)
Time Frame:	Up to 5 years
Safety Issue:
Description:	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.

Measure:	OS (Phase II)
Time Frame:	Up to 5 years
Safety Issue:
Description:	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.

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	National Cancer Institute (NCI)

Last Updated

July 20, 2021

Clinical Trials /

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