A Phase II Study of Pertuzumab and Erlotinib for Metastatic or Unresectable Neuroendocrine Tumors

• Sponsor: Pamela L. Kunz (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00947167
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 4
• Location: 1
• Arm: 1
• Duration (Months): 14
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To determine objective response rates (RR) by RECIST guideline version 1.1 for all patients treated with this strategy consisting of initial therapy with pertuzumab as a single agent and then addition of erlotinib for those who have stable disease or progressive disease at three months (Simon design).

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Tumors; Carcinoid Tumors; Adrenal Gland Tumors; Neuroblastoma; Pancreatic Neuroendocrine Tumors; Multiple Endocrine Neoplasia	Drug: pertuzumab; Drug: erlotinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Pertuzumab and Erlotinib for Metastatic or Unresectable Neuroendocrine Tumors
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pertuzumab and Erlotinib	Drug: pertuzumab; 840 mg, 420 mg, iv; Other Names: 2C4 Omnitarg Genentech ; Drug: erlotinib; 150 mg, PO; Other Names: Tarceva Erlotinib hydrochloride

Outcome Measures

Primary Outcome Measures

1. Response Rate (RR) for All Patients Treated With This Strategy (Simon Design) [CT scans are done every 4 cycles (every 12 wks)]

   RECIST v1.1 used

Secondary Outcome Measures

1. Toxicities Assessed by CTCAE Grading Criteria and Assigned Attributions Accordingly [AEs are assessed every cycle (every 3 wks)]

   by CTCAE

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subjects must be treated at Stanford University Medical Center for the entire length of study participation.

1. Patients must have histologically or cytologically confirmed well-differentiated neuroendocrine tumor. Patients must be deemed unresectable due to involvement of critical vasculature or adjacent organ invasion or have metastatic disease.

2. Patients with prior surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of > 5 years has elapsed between the primary surgery and the development of metastatic disease. Clinicians should consider biopsy of lesions to establish diagnosis of metastatic disease if there is substantial clinical ambiguity regarding the nature or source of apparent metastases.

3. Prior chemotherapy will be permitted.

4. Prior or concurrent somatostatin analogue use will be permitted.

5. Patients must have a primary or metastatic lesion measurable in at least one dimension by Modified RECIST criteria (v1.1) within 4 weeks prior to entry of study.

6. Patients must have ECOG performance status of 0-2.

7. Patients must be >= 18 years of age.

8. Laboratory values <= 2 weeks prior to randomization:

• Absolute Neutrophil Count (ANC) >= 1.5 x 109/L (>= 1500/mm3)

• Platelets (PLT) >= 50 x 109/L (>= 100,000/mm3) (or >= 25 x 109/L (>= 100,000/mm3) if thrombocytopenia is secondary to a non-myelosuppressive cause such as splenic sequestration).

• Hemoglobin (Hgb) >= 9 g/dL

• Serum creatinine <= 1.5 x ULN

• Serum bilirubin <= 1.5 x ULN (<= 3.0 x ULN if liver metastases present)

• Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) <= 3.0 x ULN (<= 5.0 x ULN if liver metastases present). Note: ERCP or percutaneous stenting may be used to normalize the liver function tests.

• Albumin >= 1.5

1. LVEF by TTE or MUGA >= 50%

2. Life expectancy >= 12 weeks

3. Ability to give written informed consent according to local guidelines

Exclusion Criteria:

1. Disease-Specific Exclusions

2. Prior full field radiotherapy <= 4 weeks or limited field radiotherapy <= 2 weeks prior to enrollment. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease.

3. Prior biologic or immunotherapy <= 2 weeks prior to registration. Patients must have recovered from all therapy-related toxicities

4. If history of other primary cancer, subject will be eligible only if she or he has:

• Curatively resected non-melanomatous skin cancer

• Curatively treated cervical carcinoma in situ

• Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 3 years

1. Concurrent use of other investigational agents and patients who have received investigational drugs <= 4 weeks prior to enrollment.

2. General Medical Exclusions

3. Subjects known to have chronic or active hepatitis B or C infection with impaired hepatic function (ineligible if AST and ALT > 3.0 x ULN).

4. History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results

5. Male subject who is not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of second-line treatment

6. Female subject (of childbearing potential, post-menopausal for less than 6 months, not surgically sterilized, or not abstinent) who is not willing to use an oral, patch or implanted contraceptive, double-barrier birth control, or an IUD during the course of the study and for 6 months following the last dose of second-line treatment

7. Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization

8. Pleural effusion or ascites that causes respiratory compromise (>= CTCAE grade 2 dyspnea)

9. Any of the following concurrent severe and/or uncontrolled medical conditions within 24 weeks of enrollment which could compromise participation in the study:

• Unstable angina pectoris

• Symptomatic congestive heart failure

• Myocardial infarction <= 6 months prior to registration and/or randomization

• Serious uncontrolled cardiac arrhythmia

• Uncontrolled diabetes

• Active or uncontrolled infection

• Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung

• Chronic renal disease

1. Patients unwilling to or unable to comply with the protocol

2. Life expectancy of less than 12 weeks

3. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored cancer study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Pamela L. Kunz
• Genentech, Inc.

Investigators

• Principal Investigator: Pamela Kunz, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pamela L. Kunz, Assistant Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT00947167
• Other Study ID Numbers: NET0008; SU-03272009-2039; 16186; END0008
• First Posted: Jul 27, 2009
• Last Update Posted: Mar 3, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Neoplasms; Neuroblastoma; Neuroendocrine Tumors; Carcinoid Tumor; Endocrine Gland Neoplasms; Multiple Endocrine Neoplasia; Erlotinib Hydrochloride; Pertuzumab

Study Results

Participant Flow

Arm/Group Title	Pertuzumab and Erlotinib
Arm/Group Description	pertuzumab: 840 mg, 420 mg, iv erlotinib: 150 mg, PO
Period Title: Pertuzumab Alone
STARTED	4
COMPLETED	4
NOT COMPLETED	0
Period Title: Pertuzumab Alone
STARTED	3
COMPLETED	3
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Pertuzumab and Erlotinib
Arm/Group Description	pertuzumab: 840 mg, 420 mg, iv erlotinib: 150 mg, PO
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	46.5
Gender (Count of Participants)
Female	2 50%
Male	2 50%

Outcome Measures

1. Primary Outcome

Title	Response Rate (RR) for All Patients Treated With This Strategy (Simon Design)
Description	RECIST v1.1 used
Time Frame	CT scans are done every 4 cycles (every 12 wks)

Outcome Measure Data

Analysis Population Description

whole cohort

Arm/Group Title	Pertuzumab and Erlotinib
Arm/Group Description	pertuzumab: 840 mg, 420 mg, iv erlotinib: 150 mg, PO
Measure Participants	4
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Toxicities Assessed by CTCAE Grading Criteria and Assigned Attributions Accordingly
Description	by CTCAE
Time Frame	AEs are assessed every cycle (every 3 wks)

Outcome Measure Data

Analysis Population Description

whole cohort

Arm/Group Title	Pertuzumab and Erlotinib
Arm/Group Description	pertuzumab: 840 mg, 420 mg, iv erlotinib: 150 mg, PO
Measure Participants	4
Count of Participants [Participants]	4 100%

Adverse Events

Time Frame	4 years
Adverse Event Reporting Description	We followed patients until death
Arm/Group Title	Pertuzumab and Erlotinib
Arm/Group Description	pertuzumab: 840 mg, 420 mg, iv erlotinib: 150 mg, PO
All Cause Mortality
	Pertuzumab and Erlotinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pertuzumab and Erlotinib
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Pertuzumab and Erlotinib
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Blood and lymphatic system disorders
Hemoglobin	3/4 (75%)	3
Leukocytes	1/4 (25%)	1
Platelets	1/4 (25%)	1
Gastrointestinal disorders
Anorexia	2/4 (50%)	2
Diarrhea	4/4 (100%)	4
Mucositis	1/4 (25%)
Nausea	2/4 (50%)	2
Taste	1/4 (25%)	1
Vomiting	3/4 (75%)	3
Hemorrhage	1/4 (25%)	1
General disorders
Fatigue	4/4 (100%)	4
Sweating	1/4 (25%)	1
Metabolism and nutrition disorders
Albumin low	1/4 (25%)	1
Alkaline Phosphatase elevation	1/4 (25%)	1
ALT elevation	3/4 (75%)	3
AST elevation	2/4 (50%)	2
Calcium low	1/4 (25%)	1
Potassium low	1/4 (25%)	1
Skin and subcutaneous tissue disorders
Hair loss	1/4 (25%)	1
Rash	4/4 (100%)	4

Limitations/Caveats

Early termination due to toxicity, thus small number of patients analyzed and limited statistical power.

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.