Adult Central Nervous System Germ Cell Tumor, Adult Teratoma, Extragonadal Seminoma, Malignant Extragonadal Germ Cell Tumor, Malignant Extragonadal Non-Seminomatous Germ Cell Tumor, Recurrent Malignant Testicular Germ Cell Tumor, Recurrent Ovarian Germ Cell Tumor, Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor, Stage IV Extragonadal Seminoma, Stage IV Ovarian Germ Cell Tumor
Conditions
Brief summary
This phase II trial studies how well palifosfamide works in treating patients with recurrent germ cell tumors. Drugs used in chemotherapy, such as palifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing
Detailed description
PRIMARY OBJECTIVES: I. To determine the response rate (complete response \[CR\]+partial response \[PR\]) of single agent palifosfamide in patients with refractory germ cell tumors. SECONDARY OBJECTIVES: I. To determine the duration of remission. II. To determine progression free and overall survival. III. To assess toxicity and tolerability of palifosfamide in patients with germ cell tumors. OUTLINE: Patients receive palifosfamide intravenously (IV) over 30 minutes on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.
Interventions
DRUGpalifosfamide
Given IV
Sponsors
Alaunos Therapeutics
Indiana University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histological or serological proof of metastatic germ cell neoplasm (gonadal or extragonadal primary) with disease not amenable to cure with either surgery or chemotherapy; patients with seminoma and nonseminoma are eligible, as are women with ovarian germ cell tumors * Patients must have evidence of recurrent or metastatic carcinoma by one or more of the criteria specified in the protocol * Patients must have received initial cisplatin based combination therapy (such as bleomycin, etoposide and cisplatin \[BEP\], etoposide and cisplatin \[EP\], VP-16 plus ifosfamide plus cisplatin \[VIP\] or similar regimens) AND demonstrated progression following the administration of at least one 'salvage' regimen for advanced germ cell neoplasm (such as high dose chemotherapy, paclitaxel/ifosfamide/cisplatin \[TIP\] or vinblastine, ifosfamide and cisplatin \[VeIP\]) * Patients must have documented failure of prior therapy as defined in the protocol * Patients are eligible after first line platinum based chemotherapy if their disease has relapsed and they have primary mediastinal non seminomatous germ cell tumor (PMNSGCT) or late relapse (\> 2 years) not amenable to surgical resection * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Laboratory test results must be within ranges established in the protocol * Potential subject must have the ability to understand (as judged by the treating physician) and willingness to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information; * Females of childbearing potential must not be pregnant or breast-feeding; male and female patients of reproductive potential must agree to use a highly reliable method of birth control from the screening visit through 28 days after the last dose of study drug
Exclusion criteria
* No active clinically serious infections as judged by the treating investigator (\> CTCAE grade 2) including known human immunodeficiency virus (HIV) infection or chronic active hepatitis B or active hepatitis C * No presence of, or history of any illness or injury to the urinary tract which may make the patient more susceptible to acute renal insufficiency in the case of potential renal adverse events * Patients must not have any cardiac disorders as defined in the protocol * No history of psychiatric illness/social situations that would limit compliance with study requirements * Patients must be at least 4 weeks post major surgery or significant traumatic injury at time of study registration * Patients must be at least 7 days post any minor surgical procedure, excluding placement of a vascular access device at the time of study registration * Patients must not have a known sensitivity to any component of palifosfamide or its known excipients * Patients with active central nervous system (CNS) metastases are excluded * Patients must not have previously been exposed to palifosfamide * Patients must have at least 3 weeks after previous radiotherapy or chemotherapy and have recovered from all major toxicities (except alopecia or grade 1 or 2 neuropathy) at the time of registration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (Defined as Partial Response or Complete Response) | Up to 2 years | The percent of patients who were shown as having a partial remission or better based on definitions of response in RECIST 1.1. At least a 30% decrease in the sum of the diameters of target lesions, in reference to baseline sum diameters, needs to be confirmed to be considered as partial response or better. Note: There were no patients with a partial or complete response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Remission in Patients Who Achieve a Partial or Complete Response | Up to 2 years | The duration of remission is from the time of confirmed partial or complete response until progression or death. Patients continuing in remission at the end of the study will be treated as censored. Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Note: There were no patients who achieved partial or complete response. |
| Progression Free Survival (PFS) | Up to 2 years | Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Time until progression, death or last evaluation will be calculated. If a patient did not progress or die, they will be censored at their last evaluation in the analysis. |
| Overall Survival | Up to 2 years | Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Time until death or last evaluation will be calculated. If a patient did not die, they will be censored in the analysis at their last known alive date. |
| Treatment Related Adverse Events Grade 3 or Higher | Up to 2 years | Number of unique patients who had a treatment related (possible, probable or definite) adverse event that was graded 3 or greater according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. |
Countries
United States
Participant flow
Recruitment details
This protocol was based on a two stage design, getting 12 patients at the first stage and 8 more if at least one CR or PR was observed in the first 12. Due to low accrual, the study was stopped at 5 patients for this study.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Palifosfamide) Patients receive palifosfamide IV over 30 minutes on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 3 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Treatment (Palifosfamide) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 36.6 years STANDARD_DEVIATION 13.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 5 |
| serious Total, serious adverse events | 2 / 5 |
Outcome results
Primary
Overall Response Rate (Defined as Partial Response or Complete Response)
The percent of patients who were shown as having a partial remission or better based on definitions of response in RECIST 1.1. At least a 30% decrease in the sum of the diameters of target lesions, in reference to baseline sum diameters, needs to be confirmed to be considered as partial response or better. Note: There were no patients with a partial or complete response.
Time frame: Up to 2 years
Population: All patients who enrolled and received treatment with at least one post baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Palifosfamide) | Overall Response Rate (Defined as Partial Response or Complete Response) | 0 percentage of participants |
Secondary
Duration of Remission in Patients Who Achieve a Partial or Complete Response
The duration of remission is from the time of confirmed partial or complete response until progression or death. Patients continuing in remission at the end of the study will be treated as censored. Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Note: There were no patients who achieved partial or complete response.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Palifosfamide) | Duration of Remission in Patients Who Achieve a Partial or Complete Response | 0 months |
Secondary
Overall Survival
Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Time until death or last evaluation will be calculated. If a patient did not die, they will be censored in the analysis at their last known alive date.
Time frame: Up to 2 years
Population: All patients who enrolled and received treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Palifosfamide) | Overall Survival | 0.95 months |
Secondary
Progression Free Survival (PFS)
Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Time until progression, death or last evaluation will be calculated. If a patient did not progress or die, they will be censored at their last evaluation in the analysis.
Time frame: Up to 2 years
Population: All patients who enrolled and received treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Palifosfamide) | Progression Free Survival (PFS) | 0.69 months |
Secondary
Treatment Related Adverse Events Grade 3 or Higher
Number of unique patients who had a treatment related (possible, probable or definite) adverse event that was graded 3 or greater according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
Time frame: Up to 2 years
Population: All patients who enrolled and received treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Palifosfamide) | Treatment Related Adverse Events Grade 3 or Higher | 1 participants |