Phase I/II Trial of Rhenium 188-P2045 in Small Cell Lung Cancer and Other Advanced Neuroendocrine Carcinomas
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|ClinicalTrials.gov Identifier: NCT02030184|
Recruitment Status : Withdrawn (PI has left the study institution.)
First Posted : January 8, 2014
Last Update Posted : June 6, 2017
There are two parts to this trial. The first study will evaluate increasing doses of Re188 P2045 in patients with advanced small cell lung cancer that has recurred after initial therapy or in patients with other advanced neuroendocrine cancers that have progressed after therapy.
Re188 P2045 is designed to attach to type 2 somatostatin receptors that are frequently expressed in those cancers and then the radioactivity from Re188 will kill the cancer cell. Only patients who have cancers that can be seen when Tc99 P2045 is administered (also seeks out the SSTR2, but Tc99 images, but does not treat the cells) will be treated.
Therefore, this approach maximizes the possibility that patients will benefit from treatment in that only those who have cancers that have the target will undergo treatment. The primary purpose of this study will be to determine the highest dose of Re188 P2045 that can be safely administered.
The second study will open after the conclusion of the first. Patients will first undergo the scan with Tc99 P2045 and then be treated with topotecan for three days. Topotecan is a standard chemotherapy drug that is approved for second line therapy for small cell and frequently used for other neuroendocrine cancers. Following that, patients will then be re-evaluated with the Tc99 P2045 scan and if it demonstrates that the tumor is positive for SSTR2, then patients will receive Re188 P2045. The goal of this study is to determine the highest dose of Re188 P2045 that can be safely administered after topotecan as well as to determine if topotecan will increase the chance that the tumor will express SSTR2.
|Condition or disease||Intervention/treatment||Phase|
|Small Cell Lung Cancer (SCLC) Neuroendocrine (NE) Tumors Large Cell Neuroendocrine (NE) Tumors||Drug: Rhenium Re 188-P2045||Phase 1 Phase 2|
This trial will be conducted patients with small cell lung cancer and other neuroendocrine cancers. These include extrapulmonary small cell, gastrointestinal carcinoid tumors that arise from pulmonary lesions, and large cell neuroendocrine (NE) tumors.
First, the dose-limiting toxicity (DLT) and maximally tolerated dose (MTD) for Rhenium Re188-P2045 alone will be determined when it is administered as a single dose, at 80, 90, 130, 170, 210 or (up to) 250 mCi/m2.
Subsequently, in the second study Rhenium Re 188-P2045 will be administered at 40, 50, 75, 85 and up to 100 per cent of the MTD determined in the first study, as a single agent or following 3 daily topotecan treatments (at 1.0 or 1.5 mg/m2) in patients with advanced neuroendocrine tumors and SSTR2 expression as determined by Technicium (Tc) Tc99m P2045 scanning.
The overall response and survival rates of patient treated with Rhenium Re188 P2045 when administered as a single dose or following topotecan will be measured.
The change (if any) in SSTR2 expression, as determined by Tc99m P2045 scanning after topotecan administration will also be determined . The correlation of pre-therapy SSTR2 expression (as determined by Tc99m P2045 scan) with overall response and survival rates will be calculated.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Dose Escalation Trial of Rhenium 188-P2045 in Small Cell Lung Cancer and Other Advanced Neuroendocrine Carcinomas as a Single Agent and in Combination With Topotecan|
|Estimated Study Start Date :||June 2017|
|Estimated Primary Completion Date :||June 2019|
|Estimated Study Completion Date :||June 2021|
Experimental: Topotecan and Rhenium Re 188 P2045
In the phase II portion of this study, patients will be screened using Technicium Tc99m. Eligible, consented patients will receive Topotecan treatment for three days, at doses of either 1.0 mg/m2 or 1.5 mg/m2. They will then receive a single dose of Rhenium Re 188-P2045, at one of the following dosage levels based on the Phase I Maximum Tolerated Dose (MTD): 40% of MTD; 50% of MTD; 75% of MTD; 85% of MTD or 100% of MTD.
Drug: Rhenium Re 188-P2045
Topotecan at 1.0 mg/m2 or 1.5 mg/m2 for 3 days, followed by single dose of Rhenium Re 188-P2045, at one of the following dosage levels based on the Phase I Maximum Tolerated Dose (MTD): 40% of MTD; 50% of MTD; 75% of MTD; 85% of MTD or 100% of MTD.
Other Name: Study B
- Determine Maximum Tolerated Dose (MTD) [ Time Frame: 28 days ]To determine, via dose-limiting toxicity (DLT), the maximally tolerated dose (MTD) for Rhenium Re188-P2045 when administered as a single dose in patients with advanced neuroendocrine tumors and SSTR2 expression as determined by Tc99m P2045 scanning.
- Overall Response Rate (ORR) [ Time Frame: 5 Years ]To describe the overall response rate (ORR) after treatment with Re188 P2045 when administered either as a single dose (Phase I) or following topotecan (Phase II) in patients with advanced neuroendocrine tumors and SSTR2 expression as determined by Tc99m P2045 scanning.
- Progression Free Survival (PFS) Rate [ Time Frame: 5 years ]To describe the progression free survival rate (PFS) of survival after treatment with Re188 P2045 when administered as a single dose or following topotecan in patients with advanced neuroendocrine tumors and SSTR2 expression as determined by Tc99m P2045 scanning
- Change in SSTR2 Expression [ Time Frame: 3 Days ]To describe the change (if any) in SSTR2 expression, as determined by Tc99m P2045 scanning after topotecan administration.
- Correlation: Pre-therapy SSTR2 Expression vs. ORR and PFS [ Time Frame: 5 years ]Calculate potential correlation between pre-therapy SSTR2 expression, as determined by Tc99m P2045 imaging, and patient Overall Response Rate (ORR) up to 5 years post treatment. Calculate potential correlation between pre-therapy SSTR2 expression, as determined by Tc99m P2045 imaging, and patient Progression Free Survival (PFS) up to 5 years post treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02030184
|United States, Maryland|
|University of Maryland Marlene & Stewart Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|