Erlotinib Plus Carboplatin and Paclitaxel in Ovarian Carcinoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00059787
• Collaborator: (none)
• Enrollment: 56
• Location: 1
• Arm: 1
• Duration (Months): 85
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This phase II trial is studying the side effects of giving erlotinib together with carboplatin and paclitaxel and to see how well it works in treating patients with stage III or stage IV ovarian, fallopian tube, or primary peritoneal cancer. Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Drugs used in chemotherapy such as carboplatin and paclitaxel use different ways to stop tumor cells from dividing so they stop growing or die.

Condition or Disease	Intervention/Treatment	Phase
Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer	Drug: paclitaxel; Drug: carboplatin; Drug: erlotinib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To establish whether the addition of OSI-774 (Tarceva) to the combination of paclitaxel and carboplatin encourages pathologic complete response (pCR) rates in patients with Stage III optimally cytoreduced (stratum 1) and Stage III suboptimally cytoreduced or Stage IV (stratum 2) ovarian, primary peritoneal or fallopian tube carcinomas when used as front line therapy.

2. To determine the degree and type of toxicity associated with this combined regimen.

SECONDARY OBJECTIVES:

1. To establish baseline epidermal growth factor receptor (EGFR), truncated EGFR (EGFRvIII), phosphorylated EGFR (pEGFR) and related signal transduction pathway protein expression levels (such as the mitogen activated protein kinase p-ERK, AKT phosphorylation and Her2/neu) in tumor samples obtained pretreatment, and to correlate these with achieving pCR.

2. To describe changes in EGFR, EGFRvIII, pEGFR expression levels and other related signal transduction pathway expression occurring during treatment with OSI-774 in combination with chemotherapy.

3. To determine the effect of the addition of OSI-774 (Tarceva) to the combination of paclitaxel and carboplatin on progression-free interval in patients with Stage III optimally cytoreduced (stratum 1) and Stage III suboptimally cytoreduced or Stage IV (stratum 2) ovarian or primary peritoneal carcinomas when used as front line therapy.

4. To determine the tolerability of twelve months of maintenance treatment with OSI-774 for patients achieving pCR, and to measure the progression-free interval for this population.

5. To document cutaneous effects of OSI 774 prospectively, and to correlate the degree of skin rash with clinical and translational endpoints.

OUTLINE: This is a non-randomized study. Patients are stratified according to disease stage (stage III with optimal residual disease vs stage III with suboptimal residual disease or stage IV).

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive oral erlotinib daily. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a pathologic complete response, those initially suboptimally debulked with a response, and patients who elect not to undergo surgical reassessment but who achieve a complete clinical response receive maintenance erlotinib for an additional 12 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Erlotinib Plus Carboplatin and Paclitaxel in Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
• Study Start Date: Apr 1, 2003
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paclitaxel, carboplatin, erlotinib Carboplatin and paclitaxel IV every 21 days x 6 cycles plus oral erlotinib	Drug: paclitaxel; Given IV; Other Names: Anzatax Asotax TAX Taxol ; Drug: carboplatin; Given IV; Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin ; Drug: erlotinib; Given PO; Other Names: CP-358,774 OSI-774

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response Rates [Up to 7 years]

   Pathologic complete response was defined as having no pathologic or cytologic evidence of disease following surgical reassessment.

2. The Percentage of Participants Experiencing Toxicty (Grade 2 and Grade 3/4) Associated With the Combined Regimen [For the duration of the study up to 7 years]

   Adverse event assessment

Secondary Outcome Measures

1. To Measure EGFR Gene Amplification in Tumor Specimens [The duration of the study for up to 7 years]

2. To Determine Progession Free Survival With the Addition of OSI-774 (Tarceva) to the Combination of Paclitaxel and Carboplatin [The duration of the study]

3. To Determine the Tolerability of Twelve Months of Maintenance Treatment [Twelve months of maintenance]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with a histologic diagnosis of primary peritoneal carcinoma, fallopian tube epithelial ovarian carcinoma, Stage III with either greater than 1 cm (suboptimal) residual disease following initial surgery, or Stage IV; all patients must either have had appropriate surgery for ovarian, fallopian tube or peritoneal carcinoma with appropriate tissue available for histologic evaluation to confirm diagnosis and stage or must be unresectable at time of diagnosis (to be determined by gynecological oncologist); cytology alone is not adequate

• Patients with the following histologic epithelial cell types are eligible: Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (NOS)

• Patients must begin chemotherapy on this study no more than twelve weeks postoperatively

• Patients must not have received chemotherapy within five years prior to enrollment

• ECOG performance status =< 2 (Karnofsky >= 60%)

• Absolute neutrophil count >= 1,500/uL

• Platelets >= 100,000/uL

• Total bilirubin =< 1.5 x institutional upper limit of normal

• AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal

• Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• Neuropathy (sensory and motor) =< CTC grade 1

• No medical contraindications to planned regimen

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had courses of chemotherapy within the five years prior to entering the study

• Patients may not be receiving any other investigational agents

• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

• History of allergic reactions attributed to compounds of similar chemical or biologic composition OSI-774 or other agents used in the study

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study because OSI-774 has the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OSI-774, breastfeeding should be discontinued if the mother is treated with OSI-774; these potential risks may also apply to other agents used in this study

• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with OSI-774 or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Montefiore Medical Center	Bronx	New York	United States	10467-2490

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Stephanie Blank, Montefiore Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00059787
• Other Study ID Numbers: NCI-2013-00026; NYU 02-30; N01CM62204
• First Posted: May 7, 2003
• Last Update Posted: Dec 1, 2015
• Last Verified: May 1, 2013

• Additional relevant MeSH terms: Adenocarcinoma; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Carcinoma, Endometrioid; Cystadenocarcinoma; Cystadenocarcinoma, Serous; Cystadenocarcinoma, Mucinous; Brenner Tumor; Paclitaxel; Carboplatin; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	A total of 56 patients were enrolled between June 2003 and December 2006.

Arm/Group Title	Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive oral erlotinib daily. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a pathologic complete response, those initially suboptimally debulked with a response, and patients who elect not to undergo surgical reassessment but who achieve a complete clinical response receive maintenance erlotinib for an additional 12 months. paclitaxel: Given IV carboplatin: Given IV erlotinib hydrochloride: Given PO laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	56
COMPLETED	36
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive oral erlotinib daily. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a pathologic complete response, those initially suboptimally debulked with a response, and patients who elect not to undergo surgical reassessment but who achieve a complete clinical response receive maintenance erlotinib for an additional 12 months. paclitaxel: Given IV carboplatin: Given IV erlotinib hydrochloride: Given PO laboratory biomarker analysis: Correlative studies
Overall Participants	56
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55.5
Sex: Female, Male (Count of Participants)
Female	56 100%
Male	0 0%
Race/Ethnicity, Customized (participants) [Number]
Black	2 3.6%
Asian	5 8.9%
White	42 75%
Other	7 12.5%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response Rates
Description	Pathologic complete response was defined as having no pathologic or cytologic evidence of disease following surgical reassessment.
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

Patients who had optimally debulking surgery

Arm/Group Title	Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive oral erlotinib daily. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a pathologic complete response, those initially suboptimally debulked with a response, and patients who elect not to undergo surgical reassessment but who achieve a complete clinical response receive maintenance erlotinib for an additional 12 months. paclitaxel: Given IV carboplatin: Given IV erlotinib hydrochloride: Given PO laboratory biomarker analysis: Correlative studies
Measure Participants	28
Number [participants]	8 14.3%

2. Primary Outcome

Title	The Percentage of Participants Experiencing Toxicty (Grade 2 and Grade 3/4) Associated With the Combined Regimen
Description	Adverse event assessment
Time Frame	For the duration of the study up to 7 years

Outcome Measure Data

Analysis Population Description

Patients enrolled on all stratums included

Arm/Group Title	Paclitaxel, Carboplatin, Erlotinib
Arm/Group Description	Carboplatin and paclitaxel IV every 21 days x 6 cycles plus oral erlotinib paclitaxel: Given IV carboplatin: Given IV erlotinib: Given PO
Measure Participants	56
Grade 3-4 neutropenia	18 32.1%
Grade 3-4 skin rash	17 30.4%
Grade 3-4 thrombocytopenia	7 12.5%
Grade 3-4 infection	7 12.5%
Grade 3-4 fatigue	5 8.9%
Grade 3 diarrhea	4 7.1%
Grade 2 skin rash	21 37.5%
Grade 2 diarrhea	7 12.5%

3. Secondary Outcome

Title	To Measure EGFR Gene Amplification in Tumor Specimens
Time Frame	The duration of the study for up to 7 years

Outcome Measure Data

Analysis Population Description

Tumor specimens were evaluated for EGFR gene amplification in 20 patients

Arm/Group Title	Paclitaxel, Carboplatin, Erlotinib
Arm/Group Description	Carboplatin and paclitaxel IV every 21 days x 6 cycles plus oral erlotinib paclitaxel: Given IV carboplatin: Given IV erlotinib: Given PO
Measure Participants	20
No amplification	11
Low-level amplification	6
moderate high amplification	3

4. Secondary Outcome

Title	To Determine Progession Free Survival With the Addition of OSI-774 (Tarceva) to the Combination of Paclitaxel and Carboplatin
Time Frame	The duration of the study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive oral erlotinib daily. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a pathologic complete response, those initially suboptimally debulked with a response, and patients who elect not to undergo surgical reassessment but who achieve a complete clinical response receive maintenance erlotinib for an additional 12 months. paclitaxel: Given IV carboplatin: Given IV erlotinib hydrochloride: Given PO laboratory biomarker analysis: Correlative studies
Measure Participants	51
Median (95% Confidence Interval) [months]	34.3

5. Secondary Outcome

Title	To Determine the Tolerability of Twelve Months of Maintenance Treatment
Time Frame	Twelve months of maintenance

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive oral erlotinib daily. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a pathologic complete response, those initially suboptimally debulked with a response, and patients who elect not to undergo surgical reassessment but who achieve a complete clinical response receive maintenance erlotinib for an additional 12 months. paclitaxel: Given IV carboplatin: Given IV erlotinib hydrochloride: Given PO laboratory biomarker analysis: Correlative studies
Measure Participants	16
No recurrence	12 21.4%
Recurrence	4 7.1%

Adverse Events

Arm/Group Title	Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive oral erlotinib daily. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a pathologic complete response, those initially suboptimally debulked with a response, and patients who elect not to undergo surgical reassessment but who achieve a complete clinical response receive maintenance erlotinib for an additional 12 months. paclitaxel: Given IV carboplatin: Given IV erlotinib hydrochloride: Given PO laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)
	Affected / at Risk (%)	# Events
Total	20/56 (35.7%)
Blood and lymphatic system disorders
Neutropenia	10/56 (17.9%)
Thrombocytopenia	4/56 (7.1%)
Gastrointestinal disorders
Constipation	1/56 (1.8%)
Diarrhea	2/56 (3.6%)
General disorders
Fatigue	3/56 (5.4%)
Hepatobiliary disorders
Alanine transaminase	1/56 (1.8%)
Aspartate transaminase	1/56 (1.8%)
Infections and infestations
Infection	4/56 (7.1%)
Skin and subcutaneous tissue disorders
Rash: desquamation	9/56 (16.1%)
Other (Not Including Serious) Adverse Events
	Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)
	Affected / at Risk (%)	# Events
Total	17/56 (30.4%)
Blood and lymphatic system disorders
Neutropenia	4/56 (7.1%)
Thrombocytopenia	9/56 (16.1%)
Anemia	9/56 (16.1%)
Gastrointestinal disorders
Constipation	10/56 (17.9%)
Diarrhea	12/56 (21.4%)
Mucositis: oral	6/56 (10.7%)
General disorders
Fatigue	13/56 (23.2%)
Nausea	10/56 (17.9%)
Pain: abdomen	5/56 (8.9%)
Metabolism and nutrition disorders
Anorexia	6/56 (10.7%)
Nervous system disorders
Neuropathy	12/56 (21.4%)
Skin and subcutaneous tissue disorders
Rash: desquamation	17/56 (30.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.