Mitotane +/- Cisplatin and Etoposide for Adrenal Cancer
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: M.D. Anderson Cancer Center
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This phase III trial studies how well mitotane alone works compared to mitotane with cisplatin and etoposide when given after surgery in treating patients with adrenocortical cancer that has a high risk of coming back (recurrence). Cortisol can cause the growth of adrenocortical tumor cells. Antihormone therapy, such as mitotane, may lessen the amount of cortisol made by the body. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether mitotane alone or mitotane with cisplatin and etoposide after surgery works better in treating patients with adrenocortical carcinoma.
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, since the trial involves chemotherapy drugs, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators or your doctor for specific guidance.
What data supports the idea that Mitotane +/- Cisplatin and Etoposide for Adrenal Cancer is an effective drug?
The available research does not provide specific data on the effectiveness of Mitotane +/- Cisplatin and Etoposide for Adrenal Cancer. The studies mentioned focus on other conditions, such as non-Hodgkin lymphoma, ovarian cancer, and Ewing sarcoma, using similar drugs. For example, one study showed a 55% response rate in non-Hodgkin lymphoma patients using a combination that included etoposide. Another study reported responses in ovarian cancer patients who had not responded to previous treatments. However, these results cannot be directly applied to adrenal cancer without specific research on that condition.12345
What safety data is available for Mitotane, Cisplatin, and Etoposide treatment?
The safety data for the combination of Cisplatin and Etoposide, sometimes with Mitotane, shows significant toxicities. In a study with advanced non-small-cell lung cancer patients, high-dose Cisplatin and Etoposide caused major myelosuppression, with 26% developing neutropenic fever, and one patient died due to toxicity. Nonhematologic toxicities included azotemia, peripheral neuropathy, nausea, vomiting, and hearing loss, which were transient and modest. Another study in Hodgkin's disease patients reported significant leukopenia, thrombocytopenia, and severe nausea and vomiting with the Cisplatin and Etoposide combination. These findings suggest that while the combination can be active, it is associated with considerable toxicity.34678
Is the drug Mitotane a promising treatment for adrenal cancer?
The information provided does not directly address the effectiveness of Mitotane for adrenal cancer. The articles focus on other drugs and treatments for different types of cancer. Therefore, based on the given information, we cannot determine if Mitotane is a promising treatment for adrenal cancer.2891011
Eligibility Criteria
This trial is for adults with Stage I-III adrenocortical cancer who've had surgery to remove the tumor. They should be at high risk of the cancer returning, have a good performance status (able to carry out daily activities), and no recent other cancers or severe health issues. Pregnant or breastfeeding individuals can't join, nor those with kidney failure, heart failure, liver problems, bone marrow suppression, neuropathy, or prior ACC treatments.Inclusion Criteria
I had adrenal cancer surgery recently and my cancer is at a high risk of coming back.
Be able to comply with the protocol procedures
Provide written informed consent
See 3 more
Exclusion Criteria
My platelet count is below 100,000/mm^3.
There is a strong chance that the cancer has spread to other parts of the body based on imaging tests.
Pregnancy or breast feeding
See 13 more
Treatment Details
Interventions
- Cisplatin (Alkylating agents)
- Etoposide (Anti-tumor antibiotic)
- Mitotane (Corticosteroid)
Trial OverviewThe study compares two approaches after surgery: one group receives only mitotane (a drug that reduces cortisol production by the body) while another group gets mitotane combined with chemotherapy drugs cisplatin and etoposide. The goal is to see which method is more effective in preventing cancer recurrence.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm B (mitotane, etoposide, cisplatin)Experimental Treatment4 Interventions
Patients receive mitotane as in Arm A. Patients also receive cisplatin IV over 2 hours on day 1 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Group II: Arm A (mitotane)Experimental Treatment2 Interventions
Patients receive mitotane PO daily on days 1-21. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.
Mitotane is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Lysodren for:
- Adrenocortical carcinoma
🇪🇺 Approved in European Union as Lysodren for:
- Adrenocortical carcinoma
- Cushing's syndrome
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
Siteman Cancer Center at Washington UniversitySaint Louis, MO
University of Michigan Comprehensive Cancer CenterAnn Arbor, MI
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
Assistance Publique - Hôpitaux de ParisCollaborator
References
Mitoxantrone, etoposide, cytarabine and prednisone as salvage therapy for refractory non-Hodgkin lymphoma (NHL) and alternated with CHOP in previously untreated patients with NHL. [2019]The treatment of relapsing or refractory high-grade malignant non-Hodgkin lymphoma (NHL) following CHOP chemotherapy remains a challenge for the clinician. In this study, 29 patients with relapsing or refractory high- or refractory low-grade malignant NHL received a combination of mitoxantrone 12 mg/m2 i.v. on days 1-2, cytarabine 100 mg/m2 i.v., b.d. d 1-2, etoposide 100 mg/m2 i.v. d 1-3 and prednisone 100 mg/m2 orally d 1-3 (ENAP). An overall response rate of 55% encouraged us to use ENAP alternated with conventional CHOP chemotherapy in 45 previously untreated NHL patients (35 with high-grade and 10 with "aggressive" low-grade malignant NHL). All patients responded with a complete remission rate (CR) of (27%) and a partial remission rate (PR) of 73% after only one course of ENAP. After a median number of 3.5 ENAP/CHOP courses, the CR and PR rate was 69 and 22%, respectively. Myelosuppression was pronounced and fever of unidentified origin and documented infections followed 59% of all cases given ENAP courses. In the last 19 previously untreated patients mitoxantrone was given at a dose of 10 mg/m2 on d 1 and cytarabine 100 mg i.v., b.d. during d 1-2. Nonhematologic toxicity was mild. We conclude that this novel chemotherapy program is effective both as first-line and salvage treatment in patients with high-grade malignant NHL. Furthermore, ENAP appears clinically to be partly non-cross resistant with CHOP chemotherapy. The dose-limiting toxicity is myelosuppression. The combination should be explored as primary therapy in combination with other chemotherapy or radiotherapy programs.
Phase II trial of intraperitoneal mitoxantrone in the management of refractory ovarian cancer. [2017]To define both the toxicity and efficacy of intraperitoneal mitoxantrone in the treatment of refractory ovarian carcinoma, 31 patients were entered onto a phase II trial of this agent delivered in a 2 L treatment volume on a monthly basis. Due to excessive local pain at the initial dose level (30 mg/m2), the amount of drug delivered with each treatment course was reduced to 20 mg/m2. Despite this reduction, 74% of patients required narcotic analgesia during treatment. In addition, there were four episodes of bowel obstruction (one requiring surgical intervention) during therapy, and two patients developed bowel obstruction and intraabdominal abscesses following the completion of treatment. Six of 18 evaluable patients (33%) whose largest tumor diameter was less than or equal to 1 cm at protocol initiation experienced surgically documented responses, compared with one of 11 patients (9%) whose largest tumor was greater than 1 cm in diameter. If the two patients exhibiting what we called a mixed response to treatment are included, seven of 21 patients previously treated with intraperitoneal cisplatin responded to this treatment program, including four patients who had failed to respond to intraperitoneal cisplatin. No responding patient has demonstrated clinical evidence of relapse with a median follow-up of 7 months (range, 3+ to 13+ months) from response laparotomy. Intraperitoneal mitoxantrone is an active treatment program in patients with small-volume refractory ovarian carcinoma, but local toxicity can be severe. Due to the toxicity encountered with this specific program, its use cannot be recommended for standard clinical practice. However, in view of the activity observed in refractory ovarian carcinoma, including responses in patients who had previously failed intraperitoneal cisplatin, it is important to continue to explore alternative therapeutic regimens using intraperitoneal mitoxantrone to reduce local toxicity while maintaining or improving efficacy.
Oral etoposide in relapsed or refractory Ewing sarcoma: a monoinstitutional experience in children and adolescents. [2017]To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ewing sarcoma.
Etoposide and carbo-or cisplatin combination therapy in refractory or relapsed Ewing sarcoma: a large retrospective study. [2022]Patients with Ewing sarcoma (EWS) who develop refractory or relapsed disease have limited treatment options. In some sarcoma centres in Europe the combination of etoposide with carbo- or cisplatin is being used for these patients, however, there are no published data available yet. Here we investigated the outcome of the combination treatment for patients with advanced Ewing sarcoma in progression after standard treatment.
Treatment for recurrent ovarian cancer. A report of 2 cases. [2014]Two cases of recurrent ovarian adenocarcinoma were resistant to standard combination chemotherapy regimens. Complete response was achieved with salvage therapy comprising cis-platinum 120 mg/m2 intravenously every 3 weeks and VP-16 (etoposide; Bristol-Myers) 200 mg per os weekly.
Phase II study of combination therapy with high-dose cisplatin, etoposide, and mitomycin in patients with advanced non-small-cell lung cancer. [2019]Forty-six patients with metastatic non-small-cell lung cancer (NSCLC) were treated with a combination of high-dose cisplatin, etoposide, and mitomycin. Thirty-four patients (74%) had a performance status of 1, and 39 patients (85%) had adenocarcinoma. Of the 42 patients evaluable for response and toxicity, four achieved a partial response (10%); no patient achieved a complete response. Seven patients who had received prior chemotherapy showed no major response. The median survival of all 42 patients was 23 weeks. Myelosuppression was the major dose-limiting toxicity for this regimen, and 12 of 46 patients (26%) developed neutropenic fever requiring hospitalization and parenteral antibiotics. Of the 12 patients with severe neutropenic fever, one patient died because of toxicity. Nonhematologic toxicities, including azotemia, peripheral neuropathy, nausea, vomiting, and hearing loss were transient and modest. We conclude that high-dose cisplatin combined with etoposide and mitomycin is a relatively toxic regimen with a low response rate. Further evaluation of the combination as given in this trial is not warranted.
Targeting the DNA repair pathway in Ewing sarcoma. [2022]Ewing sarcoma (EWS) is a tumor of the bone and soft tissue that primarily affects adolescents and young adults. With current therapies, 70% of patients with localized disease survive, but patients with metastatic or recurrent disease have a poor outcome. We found that EWS cell lines are defective in DNA break repair and are sensitive to PARP inhibitors (PARPis). PARPi-induced cytotoxicity in EWS cells was 10- to 1,000-fold higher after administration of the DNA-damaging agents irinotecan or temozolomide. We developed an orthotopic EWS mouse model and performed pharmacokinetic and pharmacodynamic studies using three different PARPis that are in clinical development for pediatric cancer. Irinotecan administered on a low-dose, protracted schedule previously optimized for pediatric patients was an effective DNA-damaging agent when combined with PARPis; it was also better tolerated than combinations with temozolomide. Combining PARPis with irinotecan and temozolomide gave complete and durable responses in more than 80% of the mice.
Phase II trial of etoposide and cis-diaminodichloro-platinum in patients with refractory and relapsed Hodgkin's disease: Cancer and Leukemia Group B (CALGB) Study 8353. [2019]A phase II study was conducted by the Cancer and Leukemia Group B (CALGB) in patients with refractory and relapsed Hodgkin's disease (HD) to assess the activity of the combination of etoposide and cis-platin. Twenty-seven patients were entered; 22 were evaluated for this report. Treatment consisted of etoposide (VP-16), 80 mg/m2 IV over 1 hour and cis-platin, 20 mg/m2 IV over 1/2-1 hour; both agents were given daily for 5 days and repeated every 21 days. All patients had received at least 2 prior chemotherapy regimens, had measurable disease, and most (86%) had a performance status of 0-1. In the 22 evaluable patients, there were 4 complete responses (18%) and 4 partial responses, for an overall response rate of 36% (95% Cl: 17.2%, 59.3%). Response duration was from 2.1 to 31 months. Significant toxicity was observed with this regimen. Ten patients (45%) had leukopenia less than 1,000/microliters, and 11 patients (50%) had thrombocytopenia less than 25,000/microliters. Serum creatinine levels reached greater than 2.0 in 14% of patients. Seven patients (32%) had severe nausea and vomiting. VP-16, cis-platin appears to be an active combination in HD; however, their combined activity is only marginally better than reported single-agent activity for VP-16 in the doses and schedule used. Further studies of related combinations in HD are currently under evaluation by the CALGB.
Phase II study of intraperitoneal cisplatin plus systemic etoposide as second-line treatment in patients with small volume residual ovarian cancer. [2019]The efficacy and toxicity of intraperitoneal (i.p.) cisplatin plus systemic etoposide were studied in 36 patients with small (
First-line cisplatin plus etoposide in high-grade metastatic neuroendocrine tumors of colon and rectum (MCRC NET): review of 8 cases. [2016]The combination of cisplatin and etoposide is effective in the treatment of small cell lung carcinomas and other high-grade neuroendocrine tumors (NET). This combination has been considered as a default treatment for patients with high-grade NET of the colon and rectum (CRC). No formal series has yet described the activity of this regimen in this patient population. A retrospective study assessing the efficacy of cisplatin plus etoposide in metastatic CRC (MCRC) NET is reported.
The role of mitozantrone in the treatment of acute leukaemia. [2018]Mitozantrone (MTZ; Novantrone), 1,4-dihydroxy-5,8-bis-[(2-[(2-hydroxyethyl)amino]ethyl]amino)-9,10- anthracenedione dihydrochloride (NSC 302739), is a synthetic anthracenedione with intercalating properties. Activity has been shown in preclinical studies in mice bearing intraperitoneal P388 and L1210 leukaemias and a variety of solid tumours. Three sequential studies to examine the activity, toxicity and scheduling of MTZ in acute leukaemia or chronic granulocytic leukaemia in myeloid transformation were undertaken in relapsed and/or refractory disease in patients up to the age of 70. Single-dose treatment up to 32 mg/m2 showed little activity but in a 5-day schedule (10 mg/m2/day) MTZ gave a 24% complete remission rate in relapsed and/or resistant acute leukaemia. In a phase III study in which MTZ was given in a similar schedule combined with a 7-day infusion of cytosine arabinoside (Ara-C; 100 mg/m2/day), 68% of patients were rendered leukaemia-free. In studies from other centres, similar very encouraging results have been obtained where MTZ has been combined with high-dose Ara-C or VP16/213.