Sorafenib in Treating Patients With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer in at Least the Second Remission

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00522301
• Collaborator: National Cancer Institute (NCI) (NIH), Bayer (Industry)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 8
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer in at least the second remission.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cavity Cancer	Drug: sorafenib tosylate; Other: immunoenzyme technique; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: pharmacological study	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine the 12-month progression-free survival (PFS) rate of women with ovarian epithelial, fallopian tube, or peritoneal cancer in second or greater remission treated with oral sorafenib tosylate.

Secondary

• To determine the safety and tolerability of prolonged treatment with oral sorafenib tosylate in women with a history of recurrent ovarian cancer.

• To correlate serum markers of angiogenesis (i.e., VEGF and bFGF) and tumor markers pAKT, HIF-1 α , and VEGF with 12-month PFS.

OUTLINE: Patients receive oral sorafenib twice a day on days 1-28. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection at baseline, every 12 weeks during study, and after completion of study therapy for pharmacokinetic studies. Samples are analyzed for soluble markers of angiogenesis (i.e., VEGF and bFGF) via ELISA and HIF-1 α, VEGF, and pAKT via IHC staining.

After completion of study treatment, patients are followed at 4 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Oral Sorafenib (Bay43-9006) In Women With Epithelial Ovarian, Fallopian Tube Or Peritoneal Carcinoma In Second Or Greater Remission
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Oral Sorafenib (BAY43-9006) Sorafenib is supplied as 200-mg tablets. Sorafenib will be administered as 400 mg orally daily x 28 days (continuous). One cycle = 28 days. There is no planned treatment interruption between cycles. Sorafenib should be taken without food (at least 1 hour before or 2 hours after eating). In the absence of intolerable toxicity, a patient may continue to receive treatment with sorafenib until disease progression, or until 24 months have elapsed.

Drug: sorafenib tosylate; Other: immunoenzyme technique; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: pharmacological study

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) Rate at 12 Months [1 year]

   All 5 patients experienced a rash. As a result, all 5 were either advised to withdraw from the protocol, or withdrew themselves from the protocol. The outcome was not met.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum

• Any stage and grade at diagnosis

• Must have received initial cytoreductive surgery and chemotherapy with ≥ 1 platinum-based chemotherapy regimen

• Persistent or recurrent disease after initial therapy

• In complete clinical remission after chemotherapy for recurrent disease, meeting all of the following criteria:

• CA125 ≤ 35 units/L

• Normal physical examination

• No definite evidence of disease by CT scan of the abdomen and pelvis

• Lymph nodes and/or soft tissue abnormalities ≤ 1.0 cm are not considered definite evidence of disease

• No known brain metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status 70-100%

• Life expectancy > 3 months

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 9.0 g/dL

• INR < 1.5 OR PT/PTT within normal limits

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Urinalysis negative for protein

• If urinalysis shows 1+ protein by dipstick or protein ≥ 30-100 mg/dL by semi-quantitative assay, a 24-hour urine collection is required

• Eligible patients must have a total urinary protein ≤ 500 mg AND measured creatinine clearance ≥ 50 mL/min from a 24-hour urine collection

• Bilirubin ≤ 1.5 times ULN

• AST and ALT ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Stable blood pressure (BP) measurement required on 3 separate days prior to the start of treatment

• No peripheral neuropathy > grade 1

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

Exclusion criteria:

• Other invasive malignancies within the past 5 years, except nonmelanoma skin cancer

• Uncontrolled concurrent illness or medical condition including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Uncontrolled diabetes

• Psychiatric illness or social situation that would preclude study compliance

• Uncontrolled hypertension defined as a persistent BP > 150/100 mm Hg (or a persistent BP > 180/90 mm Hg if the patient has a history of isolated systolic hypertension) despite ≥ 2 attempts at antihypertensive medication dosage adjustment ≥ 2 weeks apart

• Thrombolic or embolic events such as cerebrovascular accident, including transient ischemic attack, within the past 6 months

• Pulmonary hemorrhage or bleeding event ≥ grade 2 within 4 weeks of the first dose of study drug

• Other hemorrhage or bleeding event ≥ grade 3 within 4 weeks of the first dose of study drug

• Serious nonhealing wound, ulcer, or bone fracture

• Evidence or history of bleeding diathesis or coagulopathy

• Inability to take oral medications or gastrointestinal condition that compromises absorption

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib tosylate

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics

• No prior sorafenib tosylate or other inhibitors of MAPK signaling intermediates or angiogenesis inhibitors

• No prior cancer treatment that would contraindicate protocol therapy

• More than 4 weeks since prior radiotherapy

• More than 3 weeks since prior chemotherapy, biological therapy, or immunotherapy

• More than 1 week since prior hormonal therapy for cancer treatment

Exclusion criteria:

• Major surgery (i.e., laparotomy) within the past 4 weeks or minor surgery within the past 2 weeks

• Placement of a vascular access device is not considered minor surgery

• Concurrent combination antiretroviral therapy for HIV-positive patients

• Concurrent St. John wort, rifampin, or enzyme-inducing anticonvulsants (e.g., carbamazepine, phenytoin, or phenobarbital)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan - Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)
• Bayer

Investigators

• Principal Investigator: William P. Tew, MD, Memorial Sloan Kettering Cancer Center
• Principal Investigator: Paul Sabbatini, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00522301
• Other Study ID Numbers: 07-080; P30CA008748; MSKCC-07080; BAYER-MSKCC-07-080
• First Posted: Aug 29, 2007
• Last Update Posted: Feb 29, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: recurrent ovarian epithelial cancer; fallopian tube cancer; primary peritoneal cavity cancer; stage I ovarian epithelial cancer; stage II ovarian epithelial cancer; stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer
• Additional relevant MeSH terms: Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Sorafenib

Study Results

Participant Flow

Arm/Group Title	Oral Sorafenib (BAY43-9006)
Arm/Group Description	Sorafenib will be administered as 400 mg orally daily x 28 days (continuous).
Period Title: Overall Study
STARTED	6
COMPLETED	0
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Oral Sorafenib (BAY43-9006)
Arm/Group Description	Sorafenib will be administered as 400 mg orally daily x 28 days (continuous).
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 66.7%
>=65 years	2 33.3%
Sex: Female, Male (Count of Participants)
Female	6 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) Rate at 12 Months
Description	All 5 patients experienced a rash. As a result, all 5 were either advised to withdraw from the protocol, or withdrew themselves from the protocol. The outcome was not met.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Protocol terminated prior to primary outcome evaluation. All 5 patient were evaluable for toxicity only.

Arm/Group Title	Oral Sorafenib (BAY43-9006)
Arm/Group Description	Sorafenib will be administered as 400 mg orally daily x 28 days (continuous).
Measure Participants	0

Adverse Events

Arm/Group Title	Oral Sorafenib (BAY43-9006)
Arm/Group Description	Sorafenib will be administered as 400 mg orally daily x 28 days (continuous).
All Cause Mortality
	Oral Sorafenib (BAY43-9006)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Oral Sorafenib (BAY43-9006)
	Affected / at Risk (%)	# Events
Total	1/5 (20%)
Skin and subcutaneous tissue disorders
Rash: hand-foot skin reaction	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Oral Sorafenib (BAY43-9006)
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
General disorders
Pain	2/5 (40%)	2
Fatigue	5/5 (100%)	5
Metabolism and nutrition disorders
Glucose, high (hyperglycemia)	5/5 (100%)	5
Alkaline Phosphatase	5/5 (100%)	5
Nervous system disorders
Dizziness	5/5 (100%)	5
Skin and subcutaneous tissue disorders
Rash	5/5 (100%)	5

Limitations/Caveats

Early termination as it would not meet it's primary endpoint of improved survival. None of the patients completed the study.

More Information

Certain Agreements

All Principal Investigators ARE 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.