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Cisplatin and Fluorouracil Compared with Carboplatin and Paclitaxel in Treating Patients with Inoperable Locally Recurrent or Metastatic Anal Cancer

Trial Status: Closed to Accrual

This randomized phase II trial studies how well cisplatin and fluorouracil work compared with carboplatin and paclitaxel in treating patients with anal cancer that cannot be removed by surgery, has come back at or near the same place as the primary tumor, or spread to other places in the body. Drugs used in chemotherapy, such as cisplatin, fluorouracil, carboplatin, and paclitaxel, 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. It is not yet known whether cisplatin and fluorouracil are more effective than carboplatin and paclitaxel in treating anal cancer.

Inclusion Criteria

  • Inoperable, locally recurrent or metastatic disease (tumor resectability should be assessed by a local surgeon or multidisciplinary team)
  • Histological or cytological confirmation of epidermoid anal carcinoma (includes squamous, basaloid and cloacogenic lesions) from the primary tumor or a newly diagnosed recurrent/metastatic lesion
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
  • Previous definitive chemotherapy (chemo)-radiation is permitted for early stage tumors (cisplatin-based chemo-radiation is permitted but only if tumor progression/relapse occurs after 6 months from treatment completion)
  • Previous systemic chemotherapy is permitted if administered as induction treatment (=< 2 cycles) before definitive chemoradiotherapy for early stage disease and there is no evidence of tumor progression during or after treatment completion
  • Human immunodeficiency virus positive (HIV+) patients will be considered eligible if they are on highly active anti-retroviral therapy (HAART) and have a cluster of differentiation (CD)4 count of >= 200/ul (HIV+ patients who are on HAART and have a CD4 count < 200/ul are eligible if the plasma viral load is below the level of detection according to the local assay)
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/l
  • Platelets >= 100 x 10^9/l
  • Hemoglobin (Hb) >= 9 g/dl for males and >= 8 g/dl for females
  • Creatinine clearance >= 60 ml/minute
  • Serum bilirubin =< 1.5 x upper limit of normal (ULN)
  • Alanine transaminase (ALT) or aspartate transaminase (AST) =< 3 x ULN (if liver metastases are present, serum transaminases =< 5 x ULN are permitted)
  • Fertile men and women must agree to take adequate contraceptive precautions during, and for at least six months after therapy
  • Life expectancy of at least 3 months

Exclusion Criteria

  • Tumors of adenocarcinoma, melanoma, small cell and basal cell histology are excluded
  • Newly diagnosed locally advanced tumour which requires upfront systemic chemotherapy but is still amenable to curative treatment (i.e. chemotherapy followed by definitive chemoradiotherapy)
  • Locally recurrent tumor which is amenable to curative resection (as deemed by a local surgeon or multidisciplinary team)
  • Tumor relapse/progression within 6 months of completion of a cisplatin-based chemoradiotherapy regimen for the treatment of early stage tumors
  • Previous administration of > 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease
  • Tumor progression during or immediately after completion of =< 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease
  • Previous use of systemic chemotherapy or other investigational drugs for the treatment of inoperable locally recurrent or metastatic tumors (previous use of radiotherapy or chemotherapy in this setting is not an exclusion criterion if: 1) non-irradiated target tumor lesions are present at randomization for the purpose of tumor response assessment or 2) in the absence of non-irradiated target tumor lesions, progression of the irradiated tumor lesions according to the RECIST criteria version 1.1 is documented)
  • Current or recent (within 30 days of first study dosing) treatment with another investigational drug or participation in another investigational study
  • Documented or symptomatic brain metastases and/or central nervous system metastases or leptomeningeal disease
  • Major surgery performed < 28 days from treatment start
  • Palliative radiotherapy completed =< 7 days from treatment start
  • Clinically significant (i.e. active) cardiac disease (e.g. symptomatic coronary artery disease, uncontrolled cardiac arrhythmia, or myocardial infarction within the last 6 months); any history of clinically significant cardiac failure
  • History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
  • HIV+ patients who are not on HAART or have a CD4 count of < 200/ul in the presence of detectable plasma viral load according to the local assay
  • Known history of active hepatitis B or hepatitis C infection
  • Serious active infection requiring intravenous (i.v.) antibiotics at enrollment
  • Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer
  • Other clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this trial
  • Known hypersensitivity to any of the study drugs or excipients
  • Known peripheral neuropathy > grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)
  • Pre-existing hearing impairment
  • Patients planning for a live vaccine
  • Pregnant or lactating females

California

Auburn
Sutter Auburn Faith Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Berkeley
Alta Bates Summit Medical Center-Herrick Campus
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Burlingame
Mills-Peninsula Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Davis
Sutter Davis Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Los Angeles
USC / Norris Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Syma Iqbal
Phone: 323-865-0451
Modesto
Memorial Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Mountain View
Palo Alto Medical Foundation-Camino Division
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Palo Alto
Palo Alto Medical Foundation Health Care
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Roseville
Sutter Roseville Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Sacramento
Sutter Medical Center Sacramento
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
San Francisco
California Pacific Medical Center-Pacific Campus
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Santa Cruz
Palo Alto Medical Foundation-Santa Cruz
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Santa Rosa
Sutter Pacific Medical Foundation
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Sunnyvale
Palo Alto Medical Foundation-Sunnyvale
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686
Vallejo
Sutter Solano Medical Center / Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Ari David Baron
Phone: 415-209-2686

Delaware

Newark
Helen F Graham Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Gregory Andrew Masters
Phone: 302-733-6227
Medical Oncology Hematology Consultants PA
Status: CLOSED_TO_ACCRUAL
Contact: Gregory Andrew Masters
Phone: 302-733-6227
Rehoboth Beach
Beebe Health Campus
Status: CLOSED_TO_ACCRUAL
Contact: Gregory Andrew Masters
Phone: 302-733-6227
Seaford
TidalHealth Nanticoke / Allen Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Gregory Andrew Masters
Phone: 302-733-6227

Idaho

Boise
Saint Alphonsus Cancer Care Center-Boise
Status: CLOSED_TO_ACCRUAL
Contact: Tareq Al Baghdadi
Phone: 208-367-7954

Illinois

Bloomington
Illinois CancerCare-Bloomington
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Canton
Illinois CancerCare-Canton
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Carthage
Illinois CancerCare-Carthage
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Chicago
John H Stroger Jr Hospital of Cook County
Status: CLOSED_TO_ACCRUAL
Contact: Michael Russell Mullane
Phone: 312-864-6000
Northwestern University
Status: CLOSED_TO_ACCRUAL
Contact: Al Bowen Benson
Phone: 312-695-1301
University of Chicago Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Blase Nicholas Polite
Phone: 773-834-7424
Eureka
Illinois CancerCare-Eureka
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Galesburg
Illinois CancerCare-Galesburg
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Kewanee
Illinois CancerCare-Kewanee Clinic
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Macomb
Illinois CancerCare-Macomb
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
New Lenox
UC Comprehensive Cancer Center at Silver Cross
Status: CLOSED_TO_ACCRUAL
Contact: Blase Nicholas Polite
Phone: 773-834-7424
Ottawa
Illinois CancerCare-Ottawa Clinic
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Pekin
Illinois CancerCare-Pekin
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Peoria
Illinois CancerCare-Peoria
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Peru
Illinois CancerCare-Peru
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Princeton
Illinois CancerCare-Princeton
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605

Kansas

Chanute
Cancer Center of Kansas - Chanute
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Dodge City
Cancer Center of Kansas - Dodge City
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
El Dorado
Cancer Center of Kansas - El Dorado
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Fort Scott
Cancer Center of Kansas - Fort Scott
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Independence
Cancer Center of Kansas-Independence
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Kansas City
University of Kansas Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Anup K. Kasi Loknath Kumar
Phone: 913-945-7552
University of Kansas Cancer Center-West
Status: CLOSED_TO_ACCRUAL
Contact: Anup K. Kasi Loknath Kumar
Phone: 913-945-7552
Kingman
Cancer Center of Kansas-Kingman
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Lawrence
Lawrence Memorial Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Liberal
Cancer Center of Kansas-Liberal
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Manhattan
Cancer Center of Kansas-Manhattan
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
McPherson
Cancer Center of Kansas - McPherson
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Newton
Cancer Center of Kansas - Newton
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Overland Park
University of Kansas Cancer Center-Overland Park
Status: CLOSED_TO_ACCRUAL
Contact: Anup K. Kasi Loknath Kumar
Phone: 913-945-7552
Parsons
Cancer Center of Kansas - Parsons
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Pratt
Cancer Center of Kansas - Pratt
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Salina
Cancer Center of Kansas - Salina
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Wellington
Cancer Center of Kansas - Wellington
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Wichita
Ascension Via Christi Hospitals Wichita
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Cancer Center of Kansas - Wichita
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Cancer Center of Kansas-Wichita Medical Arts Tower
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374
Winfield
Cancer Center of Kansas - Winfield
Status: CLOSED_TO_ACCRUAL
Contact: Shaker R. Dakhil
Phone: 316-268-5374

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Philip Agop Philip
Phone: 313-576-9363
Flint
Genesys Hurley Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Tareq Al Baghdadi
Phone: 208-367-7954
Lansing
Sparrow Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Tareq Al Baghdadi
Phone: 208-367-7954

Missouri

Bonne Terre
Parkland Health Center-Bonne Terre
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Creve Coeur
Siteman Cancer Center at West County Hospital
Status: WITHDRAWN
Contact: Manik A Amin
Phone: 800-600-3606
Kansas City
The University of Kansas Cancer Center-South
Status: CLOSED_TO_ACCRUAL
Contact: Anup K. Kasi Loknath Kumar
Phone: 913-945-7552
University of Kansas Cancer Center - North
Status: CLOSED_TO_ACCRUAL
Contact: Anup K. Kasi Loknath Kumar
Phone: 913-945-7552
Lee's Summit
University of Kansas Cancer Center - Lee's Summit
Status: CLOSED_TO_ACCRUAL
Contact: Anup K. Kasi Loknath Kumar
Phone: 913-945-7552
Saint Louis
Missouri Baptist Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Washington University School of Medicine
Status: WITHDRAWN
Contact: Manik A Amin
Phone: 800-600-3606
Saint Peters
Siteman Cancer Center at Saint Peters Hospital
Status: WITHDRAWN
Contact: Manik A Amin
Phone: 800-600-3606
Sainte Genevieve
Sainte Genevieve County Memorial Hospital
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Sullivan
Missouri Baptist Sullivan Hospital
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605
Sunset Hills
Missouri Baptist Outpatient Center-Sunset Hills
Status: CLOSED_TO_ACCRUAL
Contact: James Lloyd Wade
Phone: 309-243-3605

North Carolina

Kinston
Vidant Oncology-Kinston
Status: CLOSED_TO_ACCRUAL
Contact: Peter Robins Watson
Phone: 252-559-2200

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: CLOSED_TO_ACCRUAL
Contact: Hassan Hatoum
Phone: 405-271-8777

Pennsylvania

Hershey
Penn State Milton S Hershey Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Nelson Shu-Sang Yee
Phone: 717-531-3779
State College
Mount Nittany Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Nelson Shu-Sang Yee
Phone: 717-531-3779

South Carolina

Charleston
Medical University of South Carolina
Status: CLOSED_TO_ACCRUAL
Contact: Paul Edward O'Brien
Phone: 843-792-9321

Texas

Dallas
Parkland Memorial Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Muhammad Shaalan Beg
Phone: 214-590-5582
UT Southwestern / Simmons Cancer Center-Dallas
Status: CLOSED_TO_ACCRUAL
Contact: Muhammad Shaalan Beg
Phone: 214-590-5582
Fort Worth
UT Southwestern / Simmons Cancer Center-Fort Worth
Status: CLOSED_TO_ACCRUAL
Contact: Muhammad Shaalan Beg
Phone: 214-590-5582
Houston
M D Anderson Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Cathy Eng
Phone: 713-792-3245

PRIMARY OBJECTIVES:

I. To evaluate best overall response rate (ORR).

SECONDARY OBJECTIVES:

I. Overall survival (OS).

II. Progression free survival (PFS).

III. Disease control rate (DCR) (stable disease [SD] or better) at 12 and 24 weeks.

IV. Best ORR of non-irradiated lesions.

V. Anti-tumor activity and magnitude of response as captured by waterfall plot analyses.

VI. Toxicity.

VII. Quality of life (QOL).

VIII. Feasibility of conducting a multicenter international study on squamous cell carcinoma of the anus (SCCA) and recruit within a reasonable time frame.

TERTIARY OBJECTIVES:

I. Explorative biomarker analysis.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive cisplatin intravenously (IV) over 1-4 hours on day 1 and fluorouracil IV continuously over 24 hours on days 1-4. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients with complications associated with the central venous access which prevent further infusion of fluorouracil and only after discussion with the Chief Investigator may receive capecitabine twice daily (BID) on days 1-4.

ARM B: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
ECOG-ACRIN Cancer Research Group

Principal Investigator
Cathy Eng

  • Primary ID EA2133
  • Secondary IDs NCI-2015-00771, NCT02051868, 13/LO/1463, 2013-001949-13, 3847, CCR 3847, InterAACT CCR 3847
  • Clinicaltrials.gov ID NCT02560298