Triciribine and Carboplatin in Ovarian Cancer - Full Text View

Purpose

The main purpose of this study is to see if we can select patients based on their cancer characteristics, to determine if Triciribine (TCN) and carboplatin are safe and tolerable when given together, and to determine if this combination of drugs can help people with recurrent ovarian cancer.

Condition	Intervention	Phase
Ovarian Cancer	Drug: Triciribine Drug: Carboplatin Drug: Ondansetron Drug: Dexamethasone Drug: Granisetron	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Leveraging a Clinico-Genomic Database to Match Patients to a Trial of Triciribine and Carboplatin: Changing Paradigms in Ovarian Cancer Clinical Research

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Dexamethasone Dexamethasone sodium phosphate Carboplatin Dexamethasone acetate Ondansetron hydrochloride Ondansetron Granisetron hydrochloride Granisetron

Genetic and Rare Diseases Information Center resources: Ovarian Cancer

U.S. FDA Resources

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
To determine the maximum tolerated dose of TCN-PM when combined with carboplatin in a Phase I clinical trial of biomarker-selected women with platinum-resistant, recurrent or persistent epithelial ovarian, fallopian tube and primary peritoneal cancer (OVCA).

Secondary Outcome Measures:

Overall Response Rate (ORR) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
The best overall response is the best time point response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest sum recorded since baseline).

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm.

Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Response and progression will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST version 1-1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
Progression Free Survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Progression-Free Survival (PFS) is defined as the duration of time from study entry to time of progression or death, whichever occurs first.

Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

Response and progression will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST version 1-1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
Duration of Stable Disease (SD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Stable Disease (SD): Neither sufficient shrinkage to qualify for Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum diameters while on study.

Response and progression will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST version 1-1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.


Estimated Enrollment:	45
Study Start Date:	September 2014
Estimated Study Completion Date:	October 2015
Estimated Primary Completion Date:	October 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Triciribine and Carboplatin Treatment (TCN) Phase I/II Clinical Trial Doses: The starting dose for this phase I study (dose level 1) will be TCN 15 mg/m^2 on days 1, 8 and 15, and Carboplatin Area Under the Curve (AUC) 5. TCN will be escalated to 25, 30, 35, then 45 mg/m^2 if dose limiting toxicities (DLTs) are not encountered. Phase II: Treat 18 additional patients at the recommended Phase II dose of triciribine + carboplatin to confirm safety and tolerability and assess Response Rate and Progression Free Survival (PFS). Ondansetron and dexamethasone - OR - granisetron and dexamethasone will be administered prior to chemotherapy.	Drug: Triciribine Triciribine (15, 25, 30, 35, or 45 mg/m^2) on days 1, 8, 15 every 21 days. To be given as a 60 minute IV infusion. Other Names: triciribine phosphate monohydrate TCN TCN-PM AKT inhibitor Drug: Carboplatin Carboplatin will be administered on day 1 every 21 days, as a 30 minute IV infusion after completion of TCN. Other Names: Paraplatin® NSC #241240 Drug: Ondansetron Ondansetron 8-16 mg IV or by mouth (PO) 30 minutes prior to administration of chemotherapy. Other Name: Zofran Drug: Dexamethasone Dexamethasone 10-20 mg IV or PO 30 minutes prior to drug administration. Other Name: Decadron Drug: Granisetron Granisetron 10 mcg/kg IV (or 2 mg PO) 30 minutes prior to chemotherapy. Other Name: Kytril

Arms

Assigned Interventions

Experimental: Triciribine and Carboplatin Treatment (TCN)

Phase I/II Clinical Trial Doses: The starting dose for this phase I study (dose level 1) will be TCN 15 mg/m^2 on days 1, 8 and 15, and Carboplatin Area Under the Curve (AUC) 5. TCN will be escalated to 25, 30, 35, then 45 mg/m^2 if dose limiting toxicities (DLTs) are not encountered.

Phase II: Treat 18 additional patients at the recommended Phase II dose of triciribine + carboplatin to confirm safety and tolerability and assess Response Rate and Progression Free Survival (PFS).

Ondansetron and dexamethasone - OR - granisetron and dexamethasone will be administered prior to chemotherapy.

Drug: Triciribine

Triciribine (15, 25, 30, 35, or 45 mg/m^2) on days 1, 8, 15 every 21 days. To be given as a 60 minute IV infusion.

Other Names:

triciribine phosphate monohydrate
TCN
TCN-PM
AKT inhibitor

Drug: Carboplatin

Carboplatin will be administered on day 1 every 21 days, as a 30 minute IV infusion after completion of TCN.

Other Names:

Paraplatin®
NSC #241240

Drug: Ondansetron

Ondansetron 8-16 mg IV or by mouth (PO) 30 minutes prior to administration of chemotherapy.

Other Name: Zofran

Drug: Dexamethasone

Dexamethasone 10-20 mg IV or PO 30 minutes prior to drug administration.

Other Name: Decadron

Drug: Granisetron

Granisetron 10 mcg/kg IV (or 2 mg PO) 30 minutes prior to chemotherapy.

Other Name: Kytril

Detailed Description:

A portion of the patient's cancer tissue, previously removed, will be analyzed for a specific protein (phosphorylated BCL-2 antagonist of cell death). If the patient is found to have high levels of this protein in their tumor, they may qualify to be in the study.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

At least 18 years of age
Histologically confirmed, measurable or non-measurable, recurrent or persistent, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma. By standard Gynecologic Oncology Group (GOG) criteria, platinum-resistant disease is defined by a disease-free interval of less than 6 months following treatment with a platinum-based regimen, or the progression of disease during platinum-based therapy.
At least one prior regimen of chemotherapy, with no maximum number of chemotherapy cycles
A serum creatinine ≤ 1.5 mg% obtained ≤ 2 weeks prior to entry
Adequate hematologic reserve obtained ≤ 2 weeks prior to entry: leukocytes ≥ 3,000 mm^3; absolute neutrophil count ≥ 1500 mm^3; platelets ≥ 100,000 mm^3
Adequate hepatocellular function: aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 3x upper limit of normal within institutional limits; bilirubin ≤ 1.5 mg/dl
Gynecologic Oncology Group (GOG) Performance Status of 0, 1, or 2
Life expectancy of at least 90 days
The patient should be off chemotherapy, biologic therapy and radiation for 28 days.
Neuropathy (sensory and motor) less than or equal to grade 1 per Common Toxicity Criteria (CTC) version 4

Exclusion Criteria:

Prior TCN-PM therapy
History of allergic reactions attributed to compounds of similar chemical or biologic composition to TCN-PM
Patients must be disease-free of prior invasive malignancies for >2 years with the exception of basal cell or squamous cell carcinoma of the skin.
Inability to give informed consent
Pregnancy
Corrected QT interval (QTc) prolongation > 450 milliseconds (msec)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01690468

Locations


United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Department of Defense

Virax Pty. Ltd,

Investigators


Principal Investigator:	Patricia L. Judson, M.D.	H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Moffitt Cancer Center Clinical Trials website This link exits the ClinicalTrials.gov site

No publications provided


Responsible Party:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT01690468 History of Changes
Other Study ID Numbers:	MCC-17035
Study First Received:	September 19, 2012
Last Updated:	December 22, 2014
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Ovarian Neoplasms Adnexal Diseases Endocrine Gland Neoplasms Endocrine System Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Neoplasms Neoplasms by Site Ovarian Diseases Urogenital Neoplasms Carboplatin Dexamethasone Granisetron Ondansetron	Anti-Anxiety Agents Anti-Inflammatory Agents Antiemetics Antineoplastic Agents Antineoplastic Agents, Hormonal Antipruritics Antipsychotic Agents Autonomic Agents Central Nervous System Agents Central Nervous System Depressants Dermatologic Agents Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on March 03, 2015