|December 20, 2007
|March 13, 2013
|December 2007 (final data collection date for primary outcome measure)
- Toxicity of Celecoxib With Concurrent Weekly Chemotherapy and Radiotherapy in the Treatment of Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck. [ Time Frame: 2 years from radiation therapy ] [ Designated as safety issue: Yes ]
Particpants experiencing Acute Toxicities > Grade 3
- Response as Evaluated by Recurrence of Diseases [ Time Frame: 2 years from end of treatment (Radiation therapy) ] [ Designated as safety issue: Yes ]
Evaluate the response to concurrent celecoxib, carboplatin, paclitaxel, and radiotherapy in the treatment of locally advanced SSC of the head and neck. Response is determined by local control only, local and distant metastasis, distant metastasis only, second primary, and surgical salvage.
- The objective of the Phase IB study is to evaluate the toxicity of celecoxib with concurrent weekly chemotherapy and radiotherapy in the treatment of locally advanced or recurrent squamous cell carcinoma of the head and neck. [ Time Frame: 2 years from RT ] [ Designated as safety issue: Yes ]
- Phase II objective is to evaluate the response to concurrent celecoxib, carboplatin, paclitaxel, and radiotherapy in the treatment of locally advanced SSC of the head and neck. Disease-free survival and local control will be evaluated. [ Time Frame: 2 years from Radaition therapy ] [ Designated as safety issue: Yes ]
|Complete list of historical versions of study NCT00581971 on ClinicalTrials.gov Archive Site
|To evaluate the expression of Cox-2 in tumor and surrounding normal tissue before and after treatment, and correlate this with outcome. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Radiosensitization With Celecoxib and Chemoradiation for Head and Neck Cancer
|Radiosensitization With a COX-2 Inhibitor (Celecoxib), With Chemoradiation for Cancer of the Head and Neck
This is a single-institution, open-label, non-randomized phase IB/II trial of celecoxib administered concurrently with carboplatin, paclitaxel, and radiation therapy in patients with locally advanced or recurrent squamous cell carcinoma of the head and neck.
Treatment for this protocol consists of radiotherapy, 70.2Gy, at 1.8Gy qd, Monday through Friday.Celecoxib 400mg bid is taken during radiotherapy, starting 1 week before radiotherapy. Carboplatin IV, AUC 2.0, weekly for weeks 1 through 7,Paclitaxel 45 mg/m2, weekly for weeks 1 through 7, and Celecoxib 400mg bid, continuing after therapy for two years or until disease progression.
|Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
- Drug: celecoxib
400mg bid starting 1 week before radiotherapy and taken through radiotherapy.
Other Name: Celebrex
- Drug: Carboplatin
IV, AUC 2.0, weekly for weeks 1 through 7
Other Name: Paraplatin
- Drug: Paclitaxel
IV 30 mg/m2, weekly for weeks 1 through 7
Other Name: Taxol
- Radiation: Radiation Therapy
70.2Gy, at 1.8Gy qd, Monday through Friday
|Experimental: Celecoxib+Carboplatin/Paclitaxel+Radiation Therapy
- Drug: celecoxib
- Drug: Carboplatin
- Drug: Paclitaxel
- Radiation: Radiation Therapy
- Aisner J, Sinibaldi V, Eisenberger M. Carboplatin in the treatment of squamous cell head and neck cancers. Semin Oncol. 1992 Feb;19(1 Suppl 2):60-5. Review.
- Altorki, N. K., R. S. Keresztes, et al. (2002). "Celecoxib (Celebrex), a selective COX-2 inhibitor, enhances the response to preoperative paclitaxel/carboplatin in early stage non-small cell lung cancer." Proceedings of the American Society of Clinical Oncology Altorki, N. K., R. S. Keresztes, et al. (2002). "Celecoxib (Celebrex), a selective COX-2 inhibitor, enhances the response to preoperative paclitaxel/carboplatin in early stage non-small cell lung cancer." Proceedings of the American Society of Clinical Oncology Abstract 101
- Bourhis J, Calais G, Eschwège F. [Chemoradiotherapy of carcinomas of the upper aerodigestive tract]. Cancer Radiother. 1998 Dec;2(6):679-88. Review. French.
- Bourhis J, Eschwege F. Radiotherapy-chemotherapy combinations in head and neck squamous cell carcinoma: overview of randomized trials. Anticancer Res. 1996 Jul-Aug;16(4C):2397-402. Review.
- Brizel DM, Albers ME, Fisher SR, Scher RL, Richtsmeier WJ, Hars V, George SL, Huang AT, Prosnitz LR. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med. 1998 Jun 18;338(25):1798-804.
- Chan G, Boyle JO, Yang EK, Zhang F, Sacks PG, Shah JP, Edelstein D, Soslow RA, Koki AT, Woerner BM, Masferrer JL, Dannenberg AJ. Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res. 1999 Mar 1;59(5):991-4.
- Choy H, Devore RF 3rd, Hande KR, Porter LL, Rosenblatt P, Yunus F, Schlabach L, Smith C, Shyr Y, Johnson DH. A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (a Vanderbilt Cancer Center Affiliate Network Study). Int J Radiat Oncol Biol Phys. 2000 Jul 1;47(4):931-7.
- Choy H, DeVore RF 3rd, Hande KR, Porter LL, Rosenblatt P, Yunus F, Schlabach L, Smith C, Shyr Y, LaPorte K, Johnson DH. Preliminary analysis of a phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small cell lung cancer. Semin Oncol. 1997 Aug;24(4 Suppl 12):S12-21-S12-26.
- Eisbruch A, Lyden T, Bradford CR, Dawson LA, Haxer MJ, Miller AE, Teknos TN, Chepeha DB, Hogikyan ND, Terrell JE, Wolf GT. Objective assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2002 May 1;53(1):23-8.
- Eisenberger M, Hornedo J, Silva H, Donehower R, Spaulding M, Van Echo D. Carboplatin (NSC-241-240): an active platinum analog for the treatment of squamous-cell carcinoma of the head and neck. J Clin Oncol. 1986 Oct;4(10):1506-9.
- Eisenberger M, Jacobs M. Simultaneous treatment with single-agent chemotherapy and radiation for locally advanced cancer of the head and neck. Semin Oncol. 1992 Aug;19(4 Suppl 11):41-6. Review.
- Forastiere AA. Paclitaxel (Taxol) for the treatment of head and neck cancer. Semin Oncol. 1994 Oct;21(5 Suppl 8):49-52. Review.
- Forastiere AA. Taxoids in head and neck cancer: the American approach. Acta Otorhinolaryngol Belg. 1999;53(3):253-7. Review.
- Frost AR, Sparks D, Grizzle WE. Methods of antigen recovery vary in their usefulness in unmasking specific antigens in immunohistochemistry. Appl Immunohistochem Mol Morphol. 2000 Sep;8(3):236-43.
- Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, Garden AS, Ridge JA, Cooper JS, Ang KK. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys. 2000 Aug 1;48(1):7-16.
- Gaffney DK, Holden J, Zempolich K, Murphy KJ, Dicker AP, Dodson M. Elevated COX-2 expression in cervical carcinoma: reduced cause-specific survival and pelvic control. Am J Clin Oncol. 2001 Oct;24(5):443-6.
- Gately S. The contributions of cyclooxygenase-2 to tumor angiogenesis. Cancer Metastasis Rev. 2000;19(1-2):19-27. Review.
- Grizzle, W. E., R. B. Myers, et al. (1998). Immunohistochemical evaluation of biomarkers in prostatic and colorectal neoplasia. John Walker's Methods in Molecular Medicine - Tumor Marker Protocols. M. Hanausek and Z. Walaszek. Totowa, NJ, Humana Press, Inc.: 143-160
- Grizzle, W. E., R. B. Myers, et al. (1998). Factors affecting immunohistochemical evaluation of biomarker expression in neoplasia. John Walker's Methods in Molecular Medicine - Tumor Marker Protocols. M. Hanausek and Z. Walaszek. Totowa, NJ, Humana Press, Inc.: 161-180.
- Gupta S, Srivastava M, Ahmad N, Bostwick DG, Mukhtar H. Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma. Prostate. 2000 Jan;42(1):73-8.
- Hanson WR, Houseman KA, Collins PW. Radiation protection in vivo by prostaglandins and related compounds of the arachidonic acid cascade. Pharmacol Ther. 1988;39(1-3):347-56. Review.
- Hanson WR, Thomas C. 16, 16-dimethyl prostaglandin E2 increases survival of murine intestinal stem cells when given before photon radiation. Radiat Res. 1983 Nov;96(2):393-8.
- Hida T, Kozaki K, Muramatsu H, Masuda A, Shimizu S, Mitsudomi T, Sugiura T, Ogawa M, Takahashi T. Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines. Clin Cancer Res. 2000 May;6(5):2006-11.
- Horiot JC, Le Fur R, N'Guyen T, Chenal C, Schraub S, Alfonsi S, Gardani G, Van Den Bogaert W, Danczak S, Bolla M, et al. Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol. 1992 Dec;25(4):231-41.
- Houchen CW, Stenson WF, Cohn SM. Disruption of cyclooxygenase-1 gene results in an impaired response to radiation injury. Am J Physiol Gastrointest Liver Physiol. 2000 Nov;279(5):G858-65.
- Hsu AL, Ching TT, Wang DS, Song X, Rangnekar VM, Chen CS. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem. 2000 Apr 14;275(15):11397-403.
- Jeremic B, Shibamoto Y, Milicic B, Nikolic N, Dagovic A, Aleksandrovic J, Vaskovic Z, Tadic L. Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol. 2000 Apr;18(7):1458-64.
- Kawamori T, Rao CV, Seibert K, Reddy BS. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res. 1998 Feb 1;58(3):409-12.
- Kishi K, Petersen S, Petersen C, Hunter N, Mason K, Masferrer JL, Tofilon PJ, Milas L. Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res. 2000 Mar 1;60(5):1326-31.
- Kokawa A, Kondo H, Gotoda T, Ono H, Saito D, Nakadaira S, Kosuge T, Yoshida S. Increased expression of cyclooxygenase-2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors. Cancer. 2001 Jan 15;91(2):333-8.
- Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ, Seibert K. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res. 2000 Mar 1;60(5):1306-11.
- Munro AJ. An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer. Br J Cancer. 1995 Jan;71(1):83-91.
- Nishimura G, Yanoma S, Mizuno H, Kawakami K, Tsukuda M. A selective cyclooxygenase-2 inhibitor suppresses tumor growth in nude mouse xenografted with human head and neck squamous carcinoma cells. Jpn J Cancer Res. 1999 Oct;90(10):1152-62.
- Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF, Taketo MM. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell. 1996 Nov 29;87(5):803-9.
- Pentland AP, Schoggins JW, Scott GA, Khan KN, Han R. Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis. 1999 Oct;20(10):1939-44.
- Petersen C, Petersen S, Milas L, Lang FF, Tofilon PJ. Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor. Clin Cancer Res. 2000 Jun;6(6):2513-20.
- Peterson HI. Tumor angiogenesis inhibition by prostaglandin synthetase inhibitors. Anticancer Res. 1986 Mar-Apr;6(2):251-3.
- Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000 Mar 18;355(9208):949-55.
- Pillsbury HC 3rd, Webster WP, Rosenman J. Prostaglandin inhibitor and radiotherapy in advanced head and neck cancers. Arch Otolaryngol Head Neck Surg. 1986 May;112(5):552-3.
- Pinto LH, Canary PC, Araújo CM, Bacelar SC, Souhami L. Prospective randomized trial comparing hyperfractionated versus conventional radiotherapy in stages III and IV oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 1991 Aug;21(3):557-62.
- Reddy BS, Rao CV, Seibert K. Evaluation of cyclooxygenase-2 inhibitor for potential chemopreventive properties in colon carcinogenesis. Cancer Res. 1996 Oct 15;56(20):4566-9.
- Rosenthal DI, Carbone DP. Taxol plus radiation for head and neck cancer. J Infus Chemother. 1995 Spring;5(2):46-54. Review.
- Ryu HS, Chang KH, Yang HW, Kim MS, Kwon HC, Oh KS. High cyclooxygenase-2 expression in stage IB cervical cancer with lymph node metastasis or parametrial invasion. Gynecol Oncol. 2000 Mar;76(3):320-5.
- Sanchíz F, Millá A, Torner J, Bonet F, Artola N, Carreño L, Moya LM, Riera D, Ripol S, Cirera L. Single fraction per day versus two fractions per day versus radiochemotherapy in the treatment of head and neck cancer. Int J Radiat Oncol Biol Phys. 1990 Dec;19(6):1347-50.
- Sawaoka H, Tsuji S, Tsujii M, Gunawan ES, Sasaki Y, Kawano S, Hori M. Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab Invest. 1999 Dec;79(12):1469-77.
- Schatz, S. P., L. B. Harrison, et al. (1997). Tumors of the nasal cavity and paranasal sinuses, nasopharynx, oral cavity, and oropharynx. Cancer: 741-801.
- Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN. Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res. 1998 Jan 15;58(2):362-6.
- Socinski MA, Marks LB, Garst J, Sibley GS, Blackstock W, Turrisi A, Herndon J, Zhou S, Anscher M, Crawford J, Shafman T, Rosenman J. Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: a preliminary report of a phase I dose escalation trial from the Carolina Conformal Therapy Consortium. Oncologist. 2001;6 Suppl 1:20-4.
- Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Khan KN, Masferrer J, Koki AT. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer. 2000 Dec 15;89(12):2637-45.
- Staar S, Rudat V, Stuetzer H, Dietz A, Volling P, Schroeder M, Flentje M, Eckel HE, Mueller RP. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1161-71. Erratum in: Int J Radiat Oncol Biol Phys 2001 Oct 1;51(2):569.
- Steinauer KK, Gibbs I, Ning S, French JN, Armstrong J, Knox SJ. Radiation induces upregulation of cyclooxygenase-2 (COX-2) protein in PC-3 cells. Int J Radiat Oncol Biol Phys. 2000 Sep 1;48(2):325-8.
- Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B, Godio L, Patterson S, Rodriguez-Bigas MA, Jester SL, King KL, Schumacher M, Abbruzzese J, DuBois RN, Hittelman WN, Zimmerman S, Sherman JW, Kelloff G. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 2000 Jun 29;342(26):1946-52.
- Suntharalingam M, Haas ML, Conley BA, Egorin MJ, Levy S, Sivasailam S, Herman JM, Jacobs MC, Gray WC, Ord RA, Aisner JA, Van Echo DA. The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys. 2000 Apr 1;47(1):49-56.
- Suntharalingam M, Haas ML, Van Echo DA, Haddad R, Jacobs MC, Levy S, Gray WC, Ord RA, Conley BA. Predictors of response and survival after concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck. Cancer. 2001 Feb 1;91(3):548-54.
- Sunwoo JB, Herscher LL, Kroog GS, Thomas GR, Ondrey FG, Duffey DC, Solomon BI, Boss C, Albert PS, McCullugh L, Rudy S, Muir C, Zhai S, Figg WD, Cook JA, Mitchell JB, Van Waes C. Concurrent paclitaxel and radiation in the treatment of locally advanced head and neck cancer. J Clin Oncol. 2001 Feb 1;19(3):800-11.
- Tsujii M, Kawano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3336-40.
- Tucker ON, Dannenberg AJ, Yang EK, Zhang F, Teng L, Daly JM, Soslow RA, Masferrer JL, Woerner BM, Koki AT, Fahey TJ 3rd. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res. 1999 Mar 1;59(5):987-90.
- Vokes EE, Weichselbaum RR, Mick R, McEvilly JM, Haraf DJ, Panje WR. Favorable long-term survival following induction chemotherapy with cisplatin, fluorouracil, and leucovorin and concomitant chemoradiotherapy for locally advanced head and neck cancer. J Natl Cancer Inst. 1992 Jun 3;84(11):877-82.
- Yoshimura R, Sano H, Masuda C, Kawamura M, Tsubouchi Y, Chargui J, Yoshimura N, Hla T, Wada S. Expression of cyclooxygenase-2 in prostate carcinoma. Cancer. 2000 Aug 1;89(3):589-96.
|December 2007 (final data collection date for primary outcome measure)
- Histologically proven primary squamous cell carcinoma arising in the oropharynx, oral cavity, hypopharynx, or larynx. Patients with recurrences after primary surgery (with no history of radiotherapy or chemotherapy) are also eligible.
- The patient has stage III or IV disease, T3 or higher, or N2 or higher, nonmetastatic. Recurrent need not satisfy these staging requirements on restating, but patients must be nonmetastatic, and either be unresectable, medically inoperable, or refuse further surgery.
- Performance status < 2 (ECOG scale) with a life expectancy of > 12 months.
- Age > 19 years.
- The patient is medically fit to tolerate a course of definitive radiation therapy.
The patient has:
- adequate hepatic function with bilirubin < 1.5 x upper limit of normal (ULN),
- transaminases (SGOT and SGPT) may be up to 2.5 x ULN if alkaline phosphatase is < ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are < ULN,
- adequate renal function with serum creatinine < 1.5 mg/dl (or estimated creatinine clearance of > 50 mL/min),
- normal serum calcium,
- adequate hematologic function as: defined by an absolute neutrophil count > 1500/ml, hematocrit > 24 %, and platelet count > 100,000/ml. Patients with hematocrit between 24 % and 30 % should undergo transfusion or treatment with epoetin, and may be enrolled.
- The patient may have had a prior malignancy but must be disease-free for 5 years prior to study entry. A history of superficial non-melanoma skin cancer or in situ carcinoma of the cervix less than three years will be allowed.
- The patient must agree to use effective contraception if procreative potential exists, and continue contraception for at least 3 months following completion of the study.
- Patient must be informed of the investigational nature of the study and sign an informed consent form.
- The patient has received radiation therapy previously to the head and neck. Previous radiotherapy for skin cancers of the head and neck are permitted if the fields do not overlap.
- The patient has received prior chemotherapy for head and neck cancer.
- The patient is pregnant or lactating.
- Squamous cell carcinoma arising in the nasopharynx, sinuses, salivary glands, or the primary is unknown.
- Non-squamous histologies (such as adenoid cystic or mucoepidermoid)
- Peripheral neuropathy > Grade 2.
- Serious non-malignant disease (e.g. congestive heart failure, uncontrolled atrial fibrillation, active hepatitis, renal failure or renal transplant).
- Scleroderma or active connective disorder (Lupus)
- Allergy to celecoxib, sulfonamides, or other NSAIDS
- Any underlying psychological condition that would prohibit the understanding and rendering of informed consent.
- Major surgery < 3 weeks prior to study entry
|19 Years and older
|Contact information is only displayed when the study is recruiting subjects
|F020703003, Link No: 000276825
|Sharon Spencer, MD,, University of Alabama at Birmingham
|University of Alabama at Birmingham
- Bristol-Myers Squibb
||Sharon Spencer, M.D.
||University of Alabama at Birmingham
|University of Alabama at Birmingham