Genasense, Carboplatin, Paclitaxel (GCP) Combination in Uveal Melanoma

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01200342
• Collaborator: Genta Incorporated (Industry)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 33
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The goal of this clinical research is to learn if the combination of Genasense (oblimersen), carboplatin, and paclitaxel (GCP) can help to control metastatic uveal melanoma. The safety of this combination will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: Genasense; Drug: Paclitaxel; Drug: Carboplatin	Phase 2

Detailed Description

Study Drugs:

Oblimersen is designed to stop the body from making a protein that makes melanoma cells resistant to chemotherapy drugs. This may make carboplatin and/or paclitaxel more effective.

Carboplatin is designed to interfere with the growth of cancer cells by stopping cell division, which may cause the cells to die.

Paclitaxel is designed to block cancer cells from dividing, which may cause them to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive oblimersen by vein over about 1 hour (+/- 5 minutes) on Days 1, 3, and 5 of each 21-day study "cycle." You will receive dexamethasone by vein over about 30 minutes before you receive oblimersen to help prevent side effects. You will take ibuprofen by mouth about 30 minutes before you receive oblimersen.

You will receive paclitaxel by vein over about 3 hours (+/- 5 minutes) on Day 3 of each cycle.

You will receive carboplatin by vein over about 30 minutes (+/- 5 minutes) on Day 3 of each cycle.

Before you receive each of these drugs, you may receive other drugs to help prevent side effects (such as nausea, vomiting, fever, and/or body aches). You may need to receive some of these drugs for some time after you receive the study drugs. Your doctor will tell you more about each of these drugs, about how they are given, and about any possible risks of receiving them.

Study Visits:

Within 3 days before each cycle, blood (about 1 tablespoon) will be drawn for routine tests.

On Day 1 of each cycle:

• You will have a physical exam, including measurement of your weight and vital signs.

• Your performance status will be recorded.

• You will be asked about any side effects you may be having.

• Women who are able to become pregnant will have a routine urine pregnancy test done.

Each week while you are on study, blood (about 1 teaspoon) will be drawn for routine tests.

Every 6 weeks, you will have the same imaging (CT and/or MRI) scans that you had at screening to check the status of the disease. If the doctor thinks it is needed, you will have a bone scan.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.

Your participation on the study will be over once you have completed the end-of-treatment visit and follow-up.

End-of-Treatment Visit:

After you stop receiving the study drugs, the following tests and procedures will be performed:

• You will have a physical exam, including measurement of your weight and vital signs.

• Your performance status will be recorded.

• Blood (about 1 tablespoon) will be drawn for routine tests.

• You will be asked about any side effects you may have had.

• You will have the same imaging (CTand /or MRI) scans that you had at screening to check the status of the disease.

• Women who are able to become pregnant will have a routine urine pregnancy test done.

Follow-up:

Every 3 months for up to 2 years after you stop receiving the study drugs, you will be called and asked about how you are doing and about any other drugs you may be receiving. Each call will last about 3 minutes.

This is an investigational study. Carboplatin and paclitaxel are FDA approved and commercially available for the treatment of a variety of cancers including breast, lung, and ovarian cancers. Oblimersen is not FDA approved or commercially available. It is currently being used for research purposes only.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Genasense-Carboplatin-Paclitaxel-Combination in Uveal Melanoma
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Genasense + Paclitaxel + Carboplatin Genasense 900 mg intravenous (IV) on a fixed-dose as a 1-hour infusion on Days 1, 3, and 5 of a 21 day cycle; Paclitaxel 175 mg/m^2 IV over 3 hours Day 3 after Genasense; Carboplatin dose in mg (target area under the concentration [AUC)]=6) administered over 30 minutes IV Piggyback (IVPB) on Day 3 after Paclitaxel.

Drug: Genasense; 900 mg by vein over 1 hour on Days 1, 3, and 5 of a 21 day cycle.; Other Names: G3139 Oblimersen ; Drug: Paclitaxel; 175 mg/m^2 by vein over 3 hours on Day 3 of a 21 day cycle following Genasense.; Other Names: Taxol ; Drug: Carboplatin; Carboplatin starting dose in mg (AUC= 6) is administered over 30 minutes IV Piggyback (IVPB). Carboplatin will be dosed after Paclitaxel dose on Day 3 every 3 weeks. The total dose of Carboplatin is calculated using a formula based upon a participant's glomerular filtration rate (GFR in mL/min) and Carboplatin target area under the concentration (AUC).; Other Names: Paraplatin

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (Percentage Subjects With Confirmed Complete or Partial Response) [Following two 3-week cycles]

   Tumor response by Response Evaluation Criteria in Solid Tumors for participants with measurable disease defined by presence of at least 1 measurable lesion at baseline: Complete Response (CR): disappearance all target lesions determined by 2 consecutive observations not less than 4 weeks apart. Partial Response (PR): >30% decrease in sum of LD of target lesions (LD) of target lesions taking as reference baseline sum LD determined by two consecutive observations not less than four weeks apart. Progression (PD): >20% increase in sum of LD of target lesions references smallest sum LD recorded since treatment started or appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking references smallest sum LD since treatment started. Measurable: lesions accurately measured in at least 1 dimension (longest diameter to be recorded) as 20 mm with conventional techniques or as 10 mm with spiral CT s

2. Number of Participants With Response [Following two 3-week cycles]

   Tumor response by Response Evaluation Criteria in Solid Tumors for participants with measurable disease defined by presence of at least 1 measurable lesion at baseline: Complete Response (CR): disappearance all target lesions determined by 2 consecutive observations not less than 4 weeks apart. Partial Response (PR): >30% decrease in sum of LD of target lesions (LD) of target lesions taking as reference baseline sum LD determined by two consecutive observations not less than four weeks apart. Progression (PD): >20% increase in sum of LD of target lesions references smallest sum LD recorded since treatment started or appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking references smallest sum LD since treatment started. Measurable: lesions accurately measured in at least 1 dimension (longest diameter to be recorded) as 20 mm with conventional techniques or as 10 mm with spiral CT s

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patients must have a history of uveal melanoma and documented metastatic disease

2. Patients must have at least one measurable lesion as per revised RECIST Criteria. A measurable lesion is defined as a non-nodal lesions that is >/= 10 mm provided the CT slice is </=5 mm in thickness or a pathologic lymph node that is >/= 15 mm on the short axis provided the CT slice is </= 5 mm in thickness or Superficial skin lesion that is >/= 10 mm in diameter as assessed using calipers. Bone lesions are not considered measurable.

3. Patients may be previously untreated or may have received prior systemic therapy but no more than one systemic cytotoxic chemotherapy regimen and one targeted therapy for metastatic disease.

4. At least 6 weeks (42 days) since any prior immunotherapy, cytokine, biologic, vaccine or other therapy unless patients have progressed during therapy. If progression occurred during therapy, patient must have recovered from any side effects before starting GCP therapy.

5. At least 4 weeks (28 days) since prior radiotherapy to > 20% of the bone marrow.

6. Lesions being used to assess disease status may not have been radiated or if so, must have progressed during or after radiation therapy.

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

8. Patients should be 18 years of age or older.

9. Patients must have adequate liver and renal function as defined by total bilirubin </=1.5 mg/dl, serum Lactate Dehydrogenase level no higher than 2.0 x UNL of the institution, transaminase (i.e., ALT and AST) levels no higher than 5 x UNL and serum creatinine </=1.5 mg/dl or estimated Creatinine Clearance >/=60 ml/min

10. Patients must have adequate bone marrow function as defined by an absolute neutrophil count of greater or equal to 1,500/mm3, and platelet count of greater or equal to 100,000/mm3.

11. Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study and in keeping with the policies of the institution.

12. Females of childbearing potential (non childbearing is defined as greater than one year post-menopausal or surgically sterilized) must use acceptable contraceptive methods (abstinence, intrauterine device, oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 7 days prior to beginning treatment on this trial. Sexually active men must also use acceptable contraceptive methods for the duration of time on study.

Exclusion Criteria:

1. Patients who have received prior therapy with Genasense, any taxane or any of cisplatin analogues for systemic disease.

2. Patients whose site of primary melanoma is not in the choroid.

3. Patients who have a current history of neoplasm other than the entry diagnosis, except for curatively treated non-melanoma skin cancer or carcinoma in situ of the prostate or cervix or other cancers treated for cure and with a disease-free survival longer than 2 years.

4. Patients with brain metastasis or history of brain metastasis (es).

5. Patients who are pregnant or breastfeeding.

6. Patients with current active infections requiring anti-infectious treatment (e.g., antibiotics, antivirals, or antifungals).

7. Patients with current peripheral neuropathy of any etiology that is greater than grade one (1).

8. Patients with unstable or serious concurrent medical conditions are excluded. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. PI or his designee shall make the final determination regarding appropriateness of enrollment.

9. Patients with a known hypersensitivity to cremophor containing anti-cancer agents.

10. Patients with one or more of the following as the only manifestations of disease are ineligible: Osteoblastic bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, carcinomatous lymphangitis, CNS metastases, lesions in a previously irradiated area that have not shown definite progression, or disease only inferred from laboratory tests or markers.

11. Patients with Gilbert's Syndrome.

12. Patients must not have had major surgery within the past 14 days.

13. Patients must not receive any concurrent chemotherapy, radiotherapy, or immunotherapy while on study.

14. Known HIV disease or infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Genta Incorporated

Investigators

• Principal Investigator: Sapna P. Patel, MD, UT MD Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Center website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01200342
• Other Study ID Numbers: 2010-0188
• First Posted: Sep 13, 2010
• Last Update Posted: Feb 11, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by M.D. Anderson Cancer Center: Uveal melanoma; Carboplatin; Genasense; Paclitaxel; oblimersen; GCP
• Additional relevant MeSH terms: Melanoma; Paclitaxel; Carboplatin; Oblimersen

Study Results

Participant Flow

Recruitment Details	Recruitment Period: December 6, 2010 to November 05, 2012. All recruitment done at The University of Texas MD Anderson Cancer Center.
Pre-assignment Detail	Study was terminated early due to decision by drug sponsor to no longer manufacture investigational drug.

Arm/Group Title	Genasense + Paclitaxel + Carboplatin
Arm/Group Description	Genasense 900 mg intravenous (IV) on a fixed-dose as a 1-hour infusion on Days 1, 3, and 5 of a 21 day cycle; Paclitaxel 175 mg/m^2 IV over 3 hours Day 3 after Genasense; Carboplatin dose in mg (target area under the concentration [AUC)]=6) administered over 30 minutes IV Piggyback (IVPB) on Day 3 after Paclitaxel.
Period Title: Overall Study
STARTED	7
COMPLETED	6
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Genasense + Paclitaxel + Carboplatin
Arm/Group Description	Genasense 900 mg intravenous (IV) on a fixed-dose as a 1-hour infusion on Days 1, 3, and 5 of a 21 day cycle; Paclitaxel 175 mg/m^2 IV over 3 hours Day 3 after Genasense; Carboplatin dose in mg (target area under the concentration [AUC)]=6) administered over 30 minutes IV Piggyback (IVPB) on Day 3 after Paclitaxel.
Overall Participants	7
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	3 42.9%
Male	4 57.1%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (Percentage Subjects With Confirmed Complete or Partial Response)
Description	Tumor response by Response Evaluation Criteria in Solid Tumors for participants with measurable disease defined by presence of at least 1 measurable lesion at baseline: Complete Response (CR): disappearance all target lesions determined by 2 consecutive observations not less than 4 weeks apart. Partial Response (PR): >30% decrease in sum of LD of target lesions (LD) of target lesions taking as reference baseline sum LD determined by two consecutive observations not less than four weeks apart. Progression (PD): >20% increase in sum of LD of target lesions references smallest sum LD recorded since treatment started or appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking references smallest sum LD since treatment started. Measurable: lesions accurately measured in at least 1 dimension (longest diameter to be recorded) as 20 mm with conventional techniques or as 10 mm with spiral CT s
Time Frame	Following two 3-week cycles

Outcome Measure Data

Analysis Population Description

The efficacy-evaluable population defined as all subjects who completed at least two cycles of therapy and had at least one post-screening assessment of target and non-target lesions. Due to inadequate enrollment of study participants, no statistical analyses were able to be performed.

Arm/Group Title	Genasense + Paclitaxel + Carboplatin
Arm/Group Description	Genasense 900 mg intravenous (IV) on a fixed-dose as a 1-hour infusion on Days 1, 3, and 5 of a 21 day cycle; Paclitaxel 175 mg/m^2 IV over 3 hours Day 3 after Genasense; Carboplatin dose in mg (target area under the concentration [AUC)]=6) administered over 30 minutes IV Piggyback (IVPB) on Day 3 after Paclitaxel.
Measure Participants	7
Number [Percentage of Participants]	0 0%

2. Primary Outcome

Title	Number of Participants With Response
Description	Tumor response by Response Evaluation Criteria in Solid Tumors for participants with measurable disease defined by presence of at least 1 measurable lesion at baseline: Complete Response (CR): disappearance all target lesions determined by 2 consecutive observations not less than 4 weeks apart. Partial Response (PR): >30% decrease in sum of LD of target lesions (LD) of target lesions taking as reference baseline sum LD determined by two consecutive observations not less than four weeks apart. Progression (PD): >20% increase in sum of LD of target lesions references smallest sum LD recorded since treatment started or appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking references smallest sum LD since treatment started. Measurable: lesions accurately measured in at least 1 dimension (longest diameter to be recorded) as 20 mm with conventional techniques or as 10 mm with spiral CT s
Time Frame	Following two 3-week cycles

Outcome Measure Data

Analysis Population Description

The efficacy-evaluable population defined as all subjects who completed at least two cycles of therapy and had at least one post-screening assessment of target and non-target lesions.

Arm/Group Title	Genasense + Paclitaxel + Carboplatin
Arm/Group Description	Genasense 900 mg intravenous (IV) on a fixed-dose as a 1-hour infusion on Days 1, 3, and 5 of a 21 day cycle; Paclitaxel 175 mg/m^2 IV over 3 hours Day 3 after Genasense; Carboplatin dose in mg (target area under the concentration [AUC)]=6) administered over 30 minutes IV Piggyback (IVPB) on Day 3 after Paclitaxel.
Measure Participants	7
Complete Response (CR)	0 0%
Partial Response (PR)	0 0%
Progressive Disease (PD)	1 14.3%
Stable Disease (SD)	6 85.7%

Adverse Events

Time Frame	Adverse events were collected from the day of initial treatment with study drug until thirty (30) days after the last treatment.
Adverse Event Reporting Description	Collection Period: April 01, 2011 to September 06, 2013.
Arm/Group Title	Genasense + Paclitaxel + Carboplatin
Arm/Group Description	Genasense 900 mg intravenous (IV) on a fixed-dose as a 1-hour infusion on Days 1, 3, and 5 of a 21 day cycle; Paclitaxel 175 mg/m^2 IV over 3 hours Day 3 after Genasense; Carboplatin dose in mg (target area under the concentration [AUC)]=6) administered over 30 minutes IV Piggyback (IVPB) on Day 3 after Paclitaxel.
All Cause Mortality
	Genasense + Paclitaxel + Carboplatin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Genasense + Paclitaxel + Carboplatin
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Genasense + Paclitaxel + Carboplatin
	Affected / at Risk (%)	# Events
Total	7/7 (100%)
Blood and lymphatic system disorders
Alanine aminotransferase increased	2/7 (28.6%)	2
Alkaline phosphatase increased	4/7 (57.1%)	4
Anemia	5/7 (71.4%)	10
Aspartate aminotransferase increased	3/7 (42.9%)	3
Blood bilirubin increased	2/7 (28.6%)	2
Hyperkalemia	1/7 (14.3%)	1
Hypoalbuminemia	1/7 (14.3%)	2
Hypokalemia	1/7 (14.3%)	1
Hypomagnesemia	1/7 (14.3%)	1
Hyponatremia	3/7 (42.9%)	6
Platelet count decreased	6/7 (85.7%)	12
Cardiac disorders
Hypotension	1/7 (14.3%)	1
Syncope	1/7 (14.3%)	1
Ear and labyrinth disorders
Dizziness	4/7 (57.1%)	6
Endocrine disorders
Hyperglycemia	4/7 (57.1%)	6
Eye disorders
Blurred vision	2/7 (28.6%)	2
Eye disorders	1/7 (14.3%)	3
Gastrointestinal disorders
Abdominal pain	1/7 (14.3%)	1
Constipation	5/7 (71.4%)	6
Diarrhea	5/7 (71.4%)	10
Gastrointestinal disorders	1/7 (14.3%)	1
General disorders
Alopecia	2/7 (28.6%)	2
Chills	4/7 (57.1%)	4
Cough	2/7 (28.6%)	3
Dry mouth	1/7 (14.3%)	1
Fatigue	6/7 (85.7%)	12
Hot flashes	1/7 (14.3%)	1
Nausea	6/7 (85.7%)	13
Pain	1/7 (14.3%)	1
Pain	1/7 (14.3%)	1
Pain	1/7 (14.3%)	1
Pain	1/7 (14.3%)	1
Pain	1/7 (14.3%)	2
Pain	2/7 (28.6%)	4
Pain	1/7 (14.3%)	1
Pain	1/7 (14.3%)	1
Vomiting	6/7 (85.7%)	10
Weight loss	2/7 (28.6%)	3
Immune system disorders
Lymphocyte count decreased	5/7 (71.4%)	8
Neutrophil count decreased	4/7 (57.1%)	12
White blood cell decreased	4/7 (57.1%)	8
Infections and infestations
Febrile neutropenia	1/7 (14.3%)	1
Fever	2/7 (28.6%)	2
Infections and infestations	1/7 (14.3%)	1
Mucositis oral	2/7 (28.6%)	5
Pruritus	3/7 (42.9%)	3
Skin infection	1/7 (14.3%)	1
Urinary tract infection	2/7 (28.6%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/7 (14.3%)	1
Edema limbs	1/7 (14.3%)	2
Generalized muscle weakness	2/7 (28.6%)	3
Musculoskeletal and connective tissue disorder	1/7 (14.3%)	1
Pain in extremity	1/7 (14.3%)	1
Peripheral sensory neuropathy	7/7 (100%)	9
Nervous system disorders
Gait disturbance	1/7 (14.3%)	1
Hallucinations	1/7 (14.3%)	1
Headache	3/7 (42.9%)	3
Psychiatric disorders
Anorexia	4/7 (57.1%)	4
Confusion	1/7 (14.3%)	1
Depression	1/7 (14.3%)	1
Renal and urinary disorders
Creatinine increased	3/7 (42.9%)	3
Hyperuricemia	1/7 (14.3%)	1
Urinary incontinence	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/7 (28.6%)	3
Skin and subcutaneous tissue disorders
Dry skin	1/7 (14.3%)	2
Pain of skin	1/7 (14.3%)	1
Rash maculo-papular	3/7 (42.9%)	5
Skin and subcutaneous tissue disorders	3/7 (42.9%)	3
Vascular disorders
Thromboembolic event	1/7 (14.3%)	2
Vascular disorders	1/7 (14.3%)	1

Limitations/Caveats

[Not Specified]

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.