Symptoms and General Pathology

All Conditions

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Blood and Lymph Conditions

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Recurrence

Esophageal Neoplasms

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Small Intestine Cancer

Antineoplastic Agents

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Oxaliplatin

Liver Extracts

Cola

oxaliplatin

management of therapy complications

Christine Rebischung

Mohamed Hebbar, MD

Gerard Lledo

Olivier Rosmorduc, MD, PhD

Jean-Baptiste Meric, MD

Thierry Andre, MD

Philippe Lechat

RATIONALE: Learning about the relationship between platinum levels in the blood and neurotoxicity in patients receiving oxaliplatin may help plan treatment and may help patients live more comfortably.

PURPOSE: This phase IV trial is studying the relationship between platinum levels in the blood and neurotoxicity in patients who are receiving oxaliplatin for gastrointestinal cancer.

OBJECTIVES:

Primary

* Determine the relationship between residual platinum levels in the blood and persistent neurotoxicity in patients receiving oxaliplatin for gastrointestinal cancer.

Secondary

* Determine the pharmacokinetics of oxaliplatin in these patients.

OUTLINE: This is an open-label, nonrandomized, multicenter study.

Patients receive oxaliplatin IV over 2 hours. Treatment repeats every 2-3 weeks in the absence of disease progression or unacceptable toxicity.

Neurological function and platinum levels in the blood are assessed at baseline, after each course of oxaliplatin, and at the end of study treatment.

PROJECTED ACCRUAL: A total of 58 patients will be accrued for this study.

Relationship Between Platinum Levels in the Blood and Neurotoxicity in Patients Who Are Receiving Oxaliplatin for Gastrointestinal Cancer

Study of the Relationship Between the Rate of Residual Platinum in the Blood and the Incidence of Persistent Neurotoxicity in Patients Treated for Gastrointestinal Cancer With Oxaliplatin

GERCOR - Multidisciplinary Oncology Cooperative Group

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma, Squamous Cell

Acquired Immunodeficiency Syndrome

HIV Infections

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Anus Diseases

Rectal Diseases

Fluorouracil

Cetuximab

Cisplatin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Immunological

All patients will receive combined modality therapy (CMT) with 2 cycles of cisplatin and 5-FU chemotherapy, given concurrently with radiation therapy. CMT consists of:

* Cetuximab 400 mg/m2 IV Day -7 (1 week before the cycle 1, Day 1 cisplatin/5-FU and RT), then 250 mg/m2 IV Days 1, 8, 15, 22, 29, 36 and 43 (a minimum of 6 and a maximum of 8 doses of cetuximab will be administered, including the loading dose).
* Cisplatin 75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2)
* 5-FU 1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2)

400 mg/m2 IV Day -7 (1 week before the cycle 1, Day 1 cisplatin/5-FU and RT), then 250 mg/m2 IV Days 1, 8, 15, 22, 29, 36 and 43 (a minimum of 6 and a maximum of 8 doses of cetuximab will be administered, including the loading dose)

cetuximab

75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2)

cisplatin

1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2)

fluorouracil

Irradiation to tumor site and inguinal nodes beginning on cycle 1, Day 1 cisplatin/5-FU (minimum 45.0 Gy \[5 weeks if given on schedule and without interruption\], maximum 54.0 Gy \[6 weeks if given on schedule and without interruption). IMRT may be used at the discretion of the treating physician.

radiation therapy

Joseph A. Sparano, MD

Lisa A. Kachnic, MD

David M. Aboulafia, MD

RATIONALE: Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cisplatin, fluorouracil, and cetuximab together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cisplatin, fluorouracil, and cetuximab together with radiation therapy works in treating patients with HIV and stage I, stage II, or stage III anal cancer.

OBJECTIVES:

Primary

* Determine the 2-year local failure rate in patients with HIV-associated stage I-IIIB anal carcinoma treated with cisplatin, fluorouracil, cetuximab, and radiotherapy.
* Determine the objective response rate (complete and partial), progression-free survival, relapse-free survival, colostomy-free survival, overall survival, quality of life, and overall toxicity in patients treated with this regimen.

Secondary

* Characterize the effect of this regimen on the underlying HIV condition by describing changes in viral load, CD4 counts, and the incidence of opportunistic illnesses, including the development of AIDS during and in the first year after treatment.
* Evaluate the effect of this regimen on anogenital human papilloma virus (HPV) infection and anal cytology.

OUTLINE: This is an open-label, multicenter study.

Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 35\*, fluorouracil IV continuously on days 1-4 and 29-32, and cisplatin IV over 1 hour on days 1 and 29. Beginning on day 1, patients undergo concurrent radiotherapy to the primary tumor 5 days a week for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

NOTE: \*Patients receiving 7 weeks of radiotherapy also receive cetuximab on days 42 and 49.

Quality of life is assessed at baseline, at the completion of study treatment, and then at months 3, 6, 12, 24, and 36.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.

Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer

Phase II Trial of Combined Modality Therapy Plus Cetuximab in HIV-Associated Anal Carcinoma

Patients will be classified into two groups for purposes of primary endpoint analysis: failure or no failure at 3 years (in the primary analysis, patients lost to follow-up prior to 3 years will be considered failures). For the secondary endpoint of objective response, patients will be classified as responders

Progression-free survival at 1 year is the percentage of patients who are alive and have not experienced progressive disease, defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, or the appearance of one or more new lesions.

Percentage of participants who are alive and have not experienced progressive disease and have not relapsed

Percentage of participants who are alive and have not had a colostomy

Percentage of participants who are alive at one year

EORTC QLQ-C30 Global Score at 1 year. The EORTC QLQ-C30 is a validated questionnaire that evaluates quality of life. The global score is an overall score for quality of life that ranges from 0 to 100. Higher scores indicate between quality of life

Delayed toxicities are defined as toxicities that occur over 90 days following treatment completion

Change in absolute CD4 counts from start of treatment to 1 year after completion of study treatment

Incidence of opportunistic illnesses, including the development of AIDS during and for 1 year after completion of study treatment

Number of participants with complete and partial responses based on the RECIST criteria

National Cancer Institute (NCI)

The Emmes Company, LLC

AIDS Malignancy Consortium

cisplatin, 5-flourouruacil, and irradiation plus cetuximab

Combined Modality Therapy

cisplatin, 5-flourouruacil, and irradiation plus cetuximab.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Director, AMC Statistical Center

Local Failure Rate at 3 Years

Progression-free Survival

Relapse-free Survival

Colostomy-free Survival at 1 Year

Overall Survival

The number of participants analyzed is the number of participants for whom quality of life questionnaires were completed at one year.

Quality of Life

Toxicity

The number of participants analyzed is the number for whom absolute CD4 count data were available at baseline at at 1 year after study completion

Changes in CD4 Counts During and for 1 Year After Completion of Study Treatment

Incidence of Opportunistic Illnesses

Anogenital Human Papilloma Virus (HPV) Infection and Anal Cytology

Objective Response Rate (Complete and Partial)

Combined modality therapy consists of cisplatin, 5-flourouracil, and irradiation plus cetuximab

Overall Study

Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity.

Given once daily 5 days a week for 5 weeks

radiotherapy

Madhur K. Garg, MD

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cetuximab may help cisplatin and fluorouracil work better by making tumor cells more sensitive to the drugs. It may also make tumor cells more sensitive to radiation therapy. Giving cetuximab together with chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with cisplatin, fluorouracil, and radiation therapy works in treating immunocompetent patients with stage I (closed to accrual as of 11/3/2008), stage II, (some stage II closed to accrual as of 11/3/2008) or stage III anal cancer.

OBJECTIVES:

Primary Objective:

* Determine whether the addition of cetuximab to combined modality therapy (CMT) comprising cisplatin, fluorouracil, and radiotherapy reduces the local failure rate by ≥ 50% at 3 years (compared with historical data) in immunocompetent patients with stage I-III invasive anal carcinoma.

Secondary Objectives:

* Determine objective response rate (complete and partial), progression-free survival, colostomy-free survival, and overall survival.
* Determine the overall toxicity of concurrent cisplatin, fluorouracil, and radiation therapy combined with cetuximab.

Exploratory Objectives:

* Evaluate the effect of cetuximab and CMT on anogenital herpes papilloma virus (HPV) infection and anal cytology.
* Evaluate whether moderate to strong expression of epidermal growth factor receptor, Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and P-Akt (as determined by immunohistochemistry) is associated with an increased risk of local failure.

OUTLINE: This is a multicenter study with two sequential arms. Arm I was closed to accrual as of 11/3/2008, and arm II opened to accrual on 8/18/2009. Patients are assigned to 1 of the 2 treatment arms.

* Arm I (closed to accrual as of 11/3/2008): Patients receive cisplatin intravenously (IV) over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57.
* Arm II (open to accrual on 8/18/2009): Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 8 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study.

Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer

Phase II Trial of Cetuximab Plus Cisplatin, 5- Fluorouracil and Radiation in Immunocompetent Patients With Anal Carcinoma

Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Local failure was defined as progression/relapse of disease in the anal canal and/or regional organs and/or regional lymph nodes after completion of protocol therapy, or progression during protocol therapy. Lost to follow-up and death (regardless of cause of death) prior to 3 years were also considered as local failures. For the calculation of local failure rate at 3 years, patients were classified into two groups (ie, coded as binary variable): failure (patients with local failure events prior to 3 years) vs. no failure (patients who still alive and had no local failure at 3 years). The binomial proportion and its exact two-sided 80% confidence interval (CI) were used to estimate it.

Overall survival (OS) is defined as time from registration to death from any cause. Patients alive are censored at the last contact date. Kaplan-Meier method was used to estimate the 3-year OS rate.

Progression-free survival (PFS) was defined as time from registration to disease progression, relapse or death (whichever occurred first), censoring cases without PFS events at the date of last disease assessment documenting the patient was free of progression/relapse. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the 3-year PFS rate.

Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible and treated patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).

Colostomy-free survival was defined as time from registration until time of colostomy or death without colostomy, censoring cases without colostomy at the data of last disease assessment documenting the patient was free of colostomy. Kaplan-Meier method was used to estimate the 3-year colostomy-free survival rate.

ECOG-ACRIN Cancer Research Group

Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity.

cetuximab: Given IV

cisplatin: Given IV

fluorouracil: Given IV

radiation therapy: Given once daily 5 days a week for 5 weeks

Arm I (Closed to Accrual as of 11/3/2008)

Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity.

cetuximab: Given IV

cisplatin: Given IV

fluorouracil: Given IV

radiation therapy: Given once daily 5 days a week for 5 weeks

Arm II (Open to Accrual on 8/18/2009)

Total

ECOG-ACRIN statistician

Null hypothesis is that the local failure rate at 3 years is no more than 35%.

The null hypothesis is that the local failure rate at 3 years is no more than 35%.

3-year Overall Survival Rate

3-year Progression-free Survival Rate

Objective Response Rate

eligible and treated patients who did not have permanent colostomy at study entry

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Relationship Between Platinum Levels in the Blood and Neurotoxicity in Patients Who Are Receiving Oxaliplatin for Gastrointestinal Cancer	NCT00274885	Cancer	oxaliplatin management of t...	18 Years -	National Cancer Institute (NCI)
Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer	NCT00324415	Anal Cancer	cetuximab cisplatin fluorouracil radiation thera...	18 Years - 120 Years	AIDS Malignancy Consortium
Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer	NCT00324415	Anal Cancer	cetuximab cisplatin fluorouracil radiation thera...	18 Years - 120 Years	AIDS Malignancy Consortium
Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer	NCT00316888	Anal Cancer	cetuximab cisplatin fluorouracil radiotherapy	18 Years -	Eastern Cooperative Oncology Group

Spots Global Cancer Trial Database for stage i anal cancer