PanGem: Panitumumab and Gemcitabine in Relapsed Ovarian Cancer

• Sponsor: Women and Infants Hospital of Rhode Island (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01296035
• Collaborator: Amgen (Industry)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 33
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a study to find out if the study drug, panitumumab, when given with gemcitabine works in treating ovarian cancer and to find out what side effects occur when they are given together.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer	Biological: Panitumumab	Phase 2

Detailed Description

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality in women, with more than 22,000 deaths per year in the United States alone. Due to the lack of effective screening strategies and subtle early symptoms, eighty percent of newly diagnosed patients have disease that is advanced. Despite cytoreductive surgery and adjuvant paclitaxel-based and platinum-based chemotherapy, 5-year survival rates continue to be less than 40%. For patients who become resistant to the platinum compounds (defined as progressive disease while on a platinum-based chemotherapy regimen (refractory) or within 6 months of completing a platinum-based chemotherapy regimen (resistant)),the outlook is particularly poor, and often heralds multi-drug resistant disease.

At the present time, the management of ovarian cancer in the platinum refractory disease state is limited to palliative intent. Patients with advanced, bulky tumors, poor performance status and nutritional compromise are unlikely to respond to therapy and may be best served by supportive care. The clinical management of refractory disease requires both patience and persistence. A patient with platinum refractory disease is begun on one of the agents with activity and an evaluation of response is made every 6-8 weeks of therapy. As long as the patient shows no signs of disease progression, the therapy can be continued unless there is unacceptable toxicity. When progressive disease is observed, another of the list of available agents can be used. It is likely that patients will receive multiple single agents during the chronic phase of their illness. Every effort should be made to balance disease response with toxicity and quality of life.

Based on this rational, this trial will be conducted to evaluate the safety and efficacy of panitumumab, a human antibody targeted to the EGF-R, and Gemcitabine, in treating women with recurrent platinum-refractory/resistant EOC. Our aim is to determine the safety and feasibility of gemcitabine and panitumumab therapy in this population and once completed, to proceed with an efficacy study using an expanded cohort.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Panitumumab and Gemcitabine as Treatment for Women With Recurrent Epithelial Ovarian Cancer.
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panitumumab and Gemcitabine Panitumumab and Gemcitabine	Biological: Panitumumab; Panitumumab 2.5 mg/kg on D1, D8, D15, and D22 and Gemcitabine 800 mg/m2 on D1, D8, and D15 of each 28 day cycle.

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate, Measured by RECIST Criteria [Every 8 weeks while on-study]

   Documentation of known measurable or evaluable disease parameters after every 2 cycles of treatment. If any patient is withdrawn for the study prior to completion of therapy a repeat evaluation will be done at that time.

Secondary Outcome Measures

1. Adverse Events, Measured by Active Version of the NCI Common Toxicity Criteria [Every 4 weeks while on-study, up to 24 weeks]

   Adverse events (AEs) will be recorded during the duration of the trial, whether or not the events are considered related to medication. All AEs considered to be related to trial therapy will be followed for resolution, including into the post-treatment period.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of metastatic, advanced, or recurrent platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancer.

• Prior first line therapy with a platinum and taxane based combination as adjuvant therapy

• Measurable disease defined by RECIST criteria

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.

• age > 18

• Karnofsky performance status > 70

• Up to three prior lines of cytotoxic therapy in the setting of recurrent disease.

• Estimated life expectancy of at least 3 months

• Women of child-bearing potential must have a negative pregnancy test

• Adequate hematopoietic function defined as:

• ANC ≥ 1500/mm3

• Platelets ≥ 100,000/mm3

• Hemoglobin ≥ 9 g/dL

• Magnesium ≥ lower limit of normal

• Calcium ≥ lower limit of normal

• Adequate renal and hepatic function defined as:

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

• SGOT ≤ 3 times ULN

• Alanine aminotransferase (ALT) ≤3xULN (if liver metastases ≤5xULN)

• Alkaline phosphatase ≤ 3 times ULN

• Creatinine ≤ 1.5 mg/dL times ULN

• Creatinine clearance ≤ 50 mL/min

Exclusion Criteria:

• Prior anti-EGFr antibody therapy (e.g., cetuximab) or treatment with small molecule EGFr inhibitors (e.g., gefitinib, erlotinib, lapatinib)

• Prior treatment with gemcitabine

• Radiotherapy ≤ 14 days prior to enrollment.

• More than three lines of systemic chemotherapy for recurrent or advanced disease. Prior hormonal therapy is allowed.

• Prior immunotherapy, or experimental or approved proteins/antibodies

• Female subject is pregnant or breast-feeding.

• Patient has received other investigational drugs within 28 days before enrollment

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

• Prior treatment with panitumumab

• Concurrent uncontrolled illness

• Ongoing or active infection

• History or active secondary cancer within the last 5 years, except for superficial basal cell skin cancers, curatively resected non-melanoma skin cancer

• Psychiatric illness or social situation that would preclude study compliance.

• History or known presence of central nervous system (CNS) metastasis

• Subjects requiring chronic use of immunosuppressive agents (e.g., methotrexate, cyclosporine)

• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) < 1 year before randomization

• History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan

• Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection

• Major surgery within 28 days or minor surgery within 14 days of study enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Women & Infants' Hospital	Providence	Rhode Island	United States	02905

Sponsors and Collaborators

• Women and Infants Hospital of Rhode Island
• Amgen

Investigators

• Principal Investigator: Carolyn McCourt, MD, Women & Infants' Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Carolyn McCourt, Dr. Carolyn McCourt, Women and Infants Hospital of Rhode Island
• ClinicalTrials.gov Identifier: NCT01296035
• Other Study ID Numbers: WIH 20050782
• First Posted: Feb 15, 2011
• Last Update Posted: Aug 25, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Carolyn McCourt, Dr. Carolyn McCourt, Women and Infants Hospital of Rhode Island: recurrent ovarian cancer; platinum-refractory ovarian cancer
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Panitumumab

Study Results

Participant Flow

Arm/Group Title	Panitumuab and Gemcitabine
Arm/Group Description	Panitumumab: Panitumumab 2.5 mg/kg on D1, D8, D15, and D22 and Gemcitabine 800 mg/m2 on D1, D8, and D15 of each 28 day cycle.
Period Title: Overall Study
STARTED	8
COMPLETED	7
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Panitumuab and Gemcitabine
Arm/Group Description	Panitumumab: Panitumumab 2.5 mg/kg on D1, D8, D15, and D22 and Gemcitabine 800 mg/m2 on D1, D8, and D15 of each 28 day cycle.
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 87.5%
>=65 years	1 12.5%
Sex: Female, Male (Count of Participants)
Female	8 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate, Measured by RECIST Criteria
Description	Documentation of known measurable or evaluable disease parameters after every 2 cycles of treatment. If any patient is withdrawn for the study prior to completion of therapy a repeat evaluation will be done at that time.
Time Frame	Every 8 weeks while on-study

Outcome Measure Data

Analysis Population Description

Due to the small number of participants, data were not collected as planned

Arm/Group Title	Panitumuab and Gemcitabine
Arm/Group Description	Panitumumab: Panitumumab 2.5 mg/kg on D1, D8, D15, and D22 and Gemcitabine 800 mg/m2 on D1, D8, and D15 of each 28 day cycle.
Measure Participants	0

2. Secondary Outcome

Title	Adverse Events, Measured by Active Version of the NCI Common Toxicity Criteria
Description	Adverse events (AEs) will be recorded during the duration of the trial, whether or not the events are considered related to medication. All AEs considered to be related to trial therapy will be followed for resolution, including into the post-treatment period.
Time Frame	Every 4 weeks while on-study, up to 24 weeks

Outcome Measure Data

Analysis Population Description

Please see results section. In short, there were 3 serious adverse events (1 thromboembolic, 1 hypomagnesemia, 1 bowel obstruction). Additional adverse events included (in decreasing order) rash, fatigue, anemia, edema, thrombocytopenia, abdominal pain, epistaxis, hypocalcemia, and calciphylaxis

Arm/Group Title	Panitumuab and Gemcitabine
Arm/Group Description	Panitumumab: Panitumumab 2.5 mg/kg on D1, D8, D15, and D22 and Gemcitabine 800 mg/m2 on D1, D8, and D15 of each 28 day cycle.
Measure Participants	8
Measure events	33
Number [participants]	8 100%

Adverse Events

Arm/Group Title	Panitumuab and Gemcitabine
Arm/Group Description	Panitumumab: Panitumumab 2.5 mg/kg on D1, D8, D15, and D22 and Gemcitabine 800 mg/m2 on D1, D8, and D15 of each 28 day cycle.
All Cause Mortality
	Panitumuab and Gemcitabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Panitumuab and Gemcitabine
	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)
Gastrointestinal disorders
Bowel obstruction	1/8 (12.5%)	3
Investigations
Hypomagnesemia	1/8 (12.5%)	2
Vascular disorders
Thromboembolic event	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Panitumuab and Gemcitabine
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
General disorders
Fatigue	6/8 (75%)	6
Abdominal pain	2/8 (25%)	2
Epistaxis	2/8 (25%)	2
Investigations
Platelet count decreased	3/8 (37.5%)	4
Anemia	5/8 (62.5%)	5
Hypocalcemia	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Rash	6/8 (75%)	6
Edema-limbs	3/8 (37.5%)	3
Calciphylaxis	1/8 (12.5%)	1

Limitations/Caveats

This study was terminated prematurely due to poor accrual. The outcome measures could not be analyzed due to the small number or participants.

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.