Oxaliplatin and Gemcitabine Followed by Radiation Therapy in the Management of Mixed Mullerian Tumors of the Uterus

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00476086
• Collaborator: Sanofi (Industry), Brigham and Women's Hospital (Other), Massachusetts General Hospital (Other)
• Enrollment: 20
• Locations: 2
• Arm: 1
• Duration (Months): 112
• Patients Per Site: 10
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine the feasibility and safety of giving the combination of oxaliplatin and gemcitabine followed by radiation therapy and to learn whether or not this drug combined with radiation therapy works in treating women with Mullerian tumors of the uterus.

Condition or Disease	Intervention/Treatment	Phase
Mixed Mullerian Tumors of the Uterus	Drug: Gemcitabine; Drug: Oxaliplatin; Radiation: Radiation	Phase 2

Detailed Description

OBJECTIVES:

Primary To determine the feasibility of dual modality therapy described as cytotoxic therapy followed by radiation therapy for the management of Malignant Mixed Mullerian Tumors (MMMTs).

Secondary

• To describe the response rate by Response Evaluation Criteria in Solid Tumors

STATISTICAL DESIGN:

This study used a two-stage design to evaluate feasibility of oxaliplatin and gemcitabine prior to radiation therapy defined as completing 3 cycles of chemotherapy. The null and alternative therapy completion rates were 25% and 50%. If 3 or more participants enrolled in the stage one cohort (n=9 participants) complete therapy than accrual would proceed to stage two (n=15 participants). If therapy was completed by at least 10 participants in the final set of 24 evaluable participants then this regimen would be deemed worthy of further study. This design had 80% power given one-sided type I error of 5% with the probability of stopping early 0.60.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Oxaliplatin and Gemcitabine Followed by Radiation Therapy in the Management of Mixed Mullerian Tumors of the Uterus
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oxaliplatin/ Gemcitabine Then Radiation Patients rcvd IV chemotherapy on days 1 and 15 of a 4-week cycle: gemcitabine 1000 mg/m2 and oxaliplatin 65 mg/m2 for up to 3 cycles. Two dose reductions per study drug were permitted. On study, chemotherapy was followed by radiation therapy (RT) within 4-6 weeks of last chemotherapy. RT regimen was tumor-volume directed.	Drug: Gemcitabine; Other Names: Gemzar ; Drug: Oxaliplatin; Other Names: Eloxatin ; Radiation: Radiation

Outcome Measures

Primary Outcome Measures

1. Chemotherapy Completion Rate [3 cycles of chemotherapy which approximates 3 months given the 28-day cycle]

   Feasibility in this study was based on the chemotherapy regimen. The chemotherapy completion rate is defined as the percentage of patients who complete 3 cycles of oxaliplatin and gemcitabine chemotherapy prior to radiation therapy.

Secondary Outcome Measures

1. Radiation Therapy Completion Rate [Radiation therapy was within 4-6 weeks of last chemotherapy dose. Participants received up to 5 weeks of radiation therapy.]

   Disease was evaluated radiologically at baseline and every X cycles on treatment; Treatment continued if radiological exam showed no progressive disease

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Surgically staged and histologically confirmed diagnosis of MMMT

• 18 years of age or older

• ECOG Performance Score of 0-2

• Adequate bone marrow function

• Adequate renal function

• Adequate hepatic function

• Patients must be recovered from both the acute and late effects of any prior surgery

Exclusion Criteria:

• Patients with an active infection

• Patients with CNS metastases

• History of prior malignancy within the past 5 years except curatively treated basal cell carcinoma of the skin, or cervical intraepithelial neoplasia

• Known hypersensitivity to any of the components of oxaliplatin or gemcitabine

• Prior radiation to the pelvis

• Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days

• Peripheral neuropathy greater or equal to Grade 2

• Stage IV visceral disease (lung and liver metastases at presentation)

• Any other medical condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent

• Known HIV or Hepatitis B or C (active, previously treated or both)

• Pregnant or breast feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Sanofi
• Brigham and Women's Hospital
• Massachusetts General Hospital

Investigators

• Principal Investigator: Susana Campos, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Susana M. Campos, MD, Medical Oncologist, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00476086
• Other Study ID Numbers: 06-063
• First Posted: May 21, 2007
• Last Update Posted: Aug 24, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Susana M. Campos, MD, Medical Oncologist, Dana-Farber Cancer Institute: oxaliplatin; gemcitabine; MMMT
• Additional relevant MeSH terms: Mixed Tumor, Mullerian; Carcinosarcoma; Uterine Neoplasms; Gemcitabine; Oxaliplatin

Study Results

Participant Flow

Recruitment Details	20 participants were enrolled between May 2007 and August 2011.

Arm/Group Title	Oxaliplatin/ Gemcitabine Then Radiation
Arm/Group Description	Patients received IV chemotherapy on days 1 and 15 of a 4-week cycle: gemcitabine 1000 mg/m2 and oxaliplatin 65 mg/m2 for up to 3 cycles. Two dose reductions per study drug were permitted. On study, chemotherapy was followed by radiation therapy (RT) within 4-6 weeks of last chemotherapy. RT regimen was tumor-volume directed.
Period Title: Overall Study
STARTED	20
Received Chemotherapy	19
Received Radiation	15
COMPLETED	15
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Oxaliplatin/ Gemcitabine Then Radiation
Arm/Group Description	Patients rcvd IV chemotherapy on days 1 and 15 of a 4-week cycle: gemcitabine 1000 mg/m2 and oxaliplatin 65 mg/m2 for up to 3 cycles. Two dose reductions per study drug were permitted. On study, chemotherapy was followed by radiation therapy (RT) within 4-6 weeks of last chemotherapy. RT regimen was tumor-volume directed. on
Overall Participants	20
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	20 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Chemotherapy Completion Rate
Description	Feasibility in this study was based on the chemotherapy regimen. The chemotherapy completion rate is defined as the percentage of patients who complete 3 cycles of oxaliplatin and gemcitabine chemotherapy prior to radiation therapy.
Time Frame	3 cycles of chemotherapy which approximates 3 months given the 28-day cycle

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all participants who started chemotherapy.

Arm/Group Title	Oxaliplatin/ Gemcitabine Then Radiation
Arm/Group Description	Patients rcvd IV chemotherapy on days 1 and 15 of a 4-week cycle: gemcitabine 1000 mg/m2 and oxaliplatin 65 mg/m2 for up to 3 cycles. Two dose reductions per study drug were permitted. On study, chemotherapy was followed by radiation therapy (RT) within 4-6 weeks of last chemotherapy. RT regimen was tumor-volume directed.
Measure Participants	19
Number (90% Confidence Interval) [percentage of participants]	100 500%

2. Secondary Outcome

Title	Radiation Therapy Completion Rate
Description	Disease was evaluated radiologically at baseline and every X cycles on treatment; Treatment continued if radiological exam showed no progressive disease
Time Frame	Radiation therapy was within 4-6 weeks of last chemotherapy dose. Participants received up to 5 weeks of radiation therapy.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all participants who started chemotherapy.

Arm/Group Title	Oxaliplatin/ Gemcitabine Then Radiation
Arm/Group Description	Patients received IV chemotherapy on days 1 and 15 of a 4-week cycle: gemcitabine 1000 mg/m2 and oxaliplatin 65 mg/m2 for up to 3 cycles. Two dose reductions per study drug were permitted. On study, chemotherapy was followed by radiation therapy (RT) within 4-6 weeks of last chemotherapy. RT regimen was tumor-volume directed.
Measure Participants	19
Number (90% Confidence Interval) [percentage of participants]	79 395%

Adverse Events

Time Frame	Assessed each cycle of chemotherapy and week of radiation therapy from time of first dose and up to day 30 post-treatment. Participants received a median of 3 cycles (1 cycle = 4 weeks) of chemotherapy and 5 weeks of radiation therapy.
Adverse Event Reporting Description	Maximum grade toxicity by type was first calculated within two subsets reflecting either adverse events with treatment-attribution of possibly, probably or definitely.related to chemotherapy or radiation therapy Serious and Other AEs were defined as grades 3-5 and grades 1-2, respectively, per CTCAEv3. (Evaluation excludes untreated participants.)
Arm/Group Title	Oxaliplatin/ Gemcitabine		Radiation
Arm/Group Description	Patients rcvd IV chemotherapy on days 1 and 15 of a 4-week cycle: gemcitabine 1000 mg/m2 and oxaliplatin 65 mg/m2 for up to 3 cycles. Two dose reductions per study drug were permitted.		On study, chemotherapy was followed by radiation therapy (RT) within 4-6 weeks of last chemotherapy. RT regimen was tumor-volume directed.
All Cause Mortality
	Oxaliplatin/ Gemcitabine		Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Oxaliplatin/ Gemcitabine		Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/19 (10.5%)		2/15 (13.3%)
Infections and infestations
Infection Gr0-2 neut, colon	1/19 (5.3%)		0/15 (0%)
Investigations
ALT, SGPT	1/19 (5.3%)		0/15 (0%)
Metabolism and nutrition disorders
Anorexia	0/19 (0%)		1/15 (6.7%)
Hyperglycemia	0/19 (0%)		1/15 (6.7%)
Other (Not Including Serious) Adverse Events
	Oxaliplatin/ Gemcitabine		Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/19 (78.9%)		14/15 (93.3%)
Blood and lymphatic system disorders
Hemoglobin	1/19 (5.3%)		0/15 (0%)
Gastrointestinal disorders
Abdomen, pain	0/19 (0%)		3/15 (20%)
Constipation	8/19 (42.1%)		3/15 (20%)
Diarrhea w/o prior colostomy	2/19 (10.5%)		11/15 (73.3%)
Dry mouth	1/19 (5.3%)		0/15 (0%)
Dyspepsia	3/19 (15.8%)		0/15 (0%)
Dysphagia	1/19 (5.3%)		0/15 (0%)
GI-other	2/19 (10.5%)		1/15 (6.7%)
Hemorrhoids	0/19 (0%)		3/15 (20%)
Nausea	10/19 (52.6%)		6/15 (40%)
Rectum, pain	0/19 (0%)		1/15 (6.7%)
Vomiting	4/19 (21.1%)		1/15 (6.7%)
General disorders
Constitutional, other	2/19 (10.5%)		0/15 (0%)
Edema limb	0/19 (0%)		1/15 (6.7%)
Fatigue	14/19 (73.7%)		9/15 (60%)
Fever w/o neutropenia	1/19 (5.3%)		0/15 (0%)
Injection site reaction	3/19 (15.8%)		0/15 (0%)
Pain NOS	1/19 (5.3%)		0/15 (0%)
Pain-other	1/19 (5.3%)		1/15 (6.7%)
Rigors/chills	1/19 (5.3%)		0/15 (0%)
Immune system disorders
Allergic reaction	0/19 (0%)		1/15 (6.7%)
Infections and infestations
Infection w/ gr3-4 neut, anal/perianal	1/19 (5.3%)		0/15 (0%)
Infection-other	0/19 (0%)		1/15 (6.7%)
Injury, poisoning and procedural complications
Radiation dermatitis	0/19 (0%)		5/15 (33.3%)
Investigations
ALT, SGPT	1/19 (5.3%)		0/15 (0%)
AST, SGOT	1/19 (5.3%)		0/15 (0%)
Leukocytes	2/19 (10.5%)		1/15 (6.7%)
Neutrophils	0/19 (0%)		2/15 (13.3%)
Platelets	2/19 (10.5%)		0/15 (0%)
Metabolism and nutrition disorders
Anorexia	1/19 (5.3%)		2/15 (13.3%)
Dehydration	0/19 (0%)		1/15 (6.7%)
Hypokalemia	1/19 (5.3%)		0/15 (0%)
Hypomagnesemia	1/19 (5.3%)		0/15 (0%)
Musculoskeletal and connective tissue disorders
Back, pain	1/19 (5.3%)		0/15 (0%)
Extremity-limb, pain	1/19 (5.3%)		0/15 (0%)
Joint, pain	0/19 (0%)		1/15 (6.7%)
Muscle, pain	3/19 (15.8%)		0/15 (0%)
Musculoskeletal/soft tissue-other	1/19 (5.3%)		0/15 (0%)
Nervous system disorders
Dizziness	1/19 (5.3%)		0/15 (0%)
Head/headache	1/19 (5.3%)		0/15 (0%)
Neurologic-other	12/19 (63.2%)		5/15 (33.3%)
Neuropathy-sensory	9/19 (47.4%)		1/15 (6.7%)
Taste disturbance	2/19 (10.5%)		0/15 (0%)
Psychiatric disorders
Anxiety	1/19 (5.3%)		0/15 (0%)
Depression	1/19 (5.3%)		0/15 (0%)
Renal and urinary disorders
Urinary frequency/urgency	0/19 (0%)		1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/19 (5.3%)		0/15 (0%)
Skin and subcutaneous tissue disorders
Alopecia	2/19 (10.5%)		0/15 (0%)
Dry skin	0/19 (0%)		1/15 (6.7%)
Hyperpigmentation	0/19 (0%)		1/15 (6.7%)
Pruritus/itching	1/19 (5.3%)		0/15 (0%)
Rash/desquamation	1/19 (5.3%)		2/15 (13.3%)
Rash: acne/acneiform	2/19 (10.5%)		0/15 (0%)
Skin, pain	1/19 (5.3%)		2/15 (13.3%)
Skin-other	2/19 (10.5%)		0/15 (0%)
Vascular disorders
Flushing	1/19 (5.3%)		1/15 (6.7%)
Hot flashes	1/19 (5.3%)		1/15 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.