CLINICAL TRIALS PROFILE FOR MITOTANE

All Clinical Trials for mitotane

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001339 ↗	A Study of Combination Chemotherapy and Surgical Resection in the Treatment of Adrenocortical Carcinoma: Continuous Infusion Doxorubicin, Vincristine and Etoposide With Daily Mitotane Before and After Surgical Resection	Completed	National Cancer Institute (NCI)	Phase 2	1993-08-01	Patients who have no response to preoperative chemotherapy and no residual disease following surgery on Regimen A are treated on Regimen B postoperatively. The following acronyms are used: DDD Mitotane, NSC-38721 DOX Doxorubicin, NSC-123127 VCR Vincristine, NSC-67574 VP-16 Etoposide, NSC-141540 Regimen A: 4-Drug Combination Chemotherapy followed by Surgery followed by 4-Drug Combination Chemotherapy. DDD/DOX/VCR/VP-16; followed by surgical debulking; followed by DDD/DOX/VCR/VP-16. Regimen B: Single-Agent Chemotherapy. DDD.
NCT00002921 ↗	S9427, Suramin in Treating Patients With Stage III or Stage IV Adrenocortical Cancer Incurable by Surgery	Terminated	National Cancer Institute (NCI)	Phase 2	1997-03-01	RATIONALE: Some tumors need growth factors produced by the body to keep growing. Suramin may interfere with the growth factor and stop the tumor from growing. PURPOSE: Phase II trial to study the effectiveness of suramin in treating patients with stage III or stage IV adrenocortical cancer.
NCT00002921 ↗	S9427, Suramin in Treating Patients With Stage III or Stage IV Adrenocortical Cancer Incurable by Surgery	Terminated	Southwest Oncology Group	Phase 2	1997-03-01	RATIONALE: Some tumors need growth factors produced by the body to keep growing. Suramin may interfere with the growth factor and stop the tumor from growing. PURPOSE: Phase II trial to study the effectiveness of suramin in treating patients with stage III or stage IV adrenocortical cancer.
NCT00071058 ↗	Surgery Plus Chemotherapy (Doxorubicin, Vincristine and Etoposide), Mitotane, and Tariquidar to Treat Adrenocortical Cancer	Completed	National Cancer Institute (NCI)	Phase 2	2003-10-01	This study will examine the safety and effectiveness of treating adrenocortical cancer with combination chemotherapy using doxorubicin, vincristine, and etoposide in addition to the drugs mitotane and tariquidar and, when possible, surgery. Adrenocortical cancer cells have a large amount of a protein called P-glycoprotein that "pumps" anti-cancer drugs out of the cells, decreasing their effectiveness. Continuous infusions of doxorubicin, vincristine, and etoposide may improve chemotherapy results by blocking the P-glycoprotein pump, as may use of tariquidar, an experimental drug that is known to block the P-glycoprotein pump. Patients 18 years of age and older with adrenocortical cancer that has recurred, spread, or cannot be treated surgically may be eligible for this study. Candidates will be screened with a medical history and physical examination; review of pathology slides; blood tests; electrocardiogram (EKG); imaging tests, including computed tomography (CT) of the chest, abdomen and pelvis; chest x-ray; and possibly a bone scan or other imaging tests needed to evaluate the cancer, urine studies, and an echocardiogram. Also, a biopsy (removal of a small sample of tumor tissue) may be required if a specimen is not available to confirm the cancer. Participants will undergo the following tests and procedures: - Tumor biopsy. Before starting chemotherapy, a small piece of tumor is removed to study the P-glycoprotein pump and to determine the tumor genetics. - Blood draw. Blood is drawn before treatment begins to establish baseline levels for future blood tests. - Central venous catheter placement. A specially trained physician places a plastic tube into a major vein in the chest. The tube is used to give the study drugs and other medications and to withdraw blood samples. It can stay in the body for months or be removed after each treatment is completed. The tube placement is done under a local anesthetic in the radiology department or operating room. - Chemotherapy. Treatment cycles are 21 days. Doxorubicin, vincristine, and etoposide are given through the central venous catheter by an infusion pump continuously over 96 hours starting day 1 of each cycle. The dose of these drugs may be increased or decreased from cycle to cycle, based on side effects. Mitotane is given in pill form starting day 1 of cycle 1 and is taken every day throughout the entire study. The mitotane dose is gradually increased as long as the side effects are tolerable. Tariquidar is given through the central venous catheter as a 30-minute infusion on days 1 and 3 of every cycle. The tariquidar dose remains the same throughout the study. Treatment will continue for two cycles after all the cancer is gone, or until surgery is done to remove some or all of the remaining cancer, or, if surgery is not an option, until the cancer has grown to where it is defined as progressive disease. - Nuclear scans. A nuclear scan is done before treatment begins and again on day 1 or day 3 of the first treatment cycle after administration of tariquidar to evaluate the P glycoprotein response to treatment. - Computed tomography (CT) scans. These scans are done every two treatment cycles to follow disease progress. - Surgery. Surgery to remove areas of cancer may be considered at any point during the study (including before beginning treatment), if it is deemed beneficial. Treatment with the study drugs will begin or resume after surgery. The length of treatment will depend on the response to treatment before the surgery and on whether there is any cancer remaining after the surgery.
NCT00094497 ↗	Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)	Completed	German Federal Ministry of Education and Research	Phase 3	2004-06-01	The purpose of this study is to determine whether treatment with etoposide, doxorubicin, cisplatin and mitotane (EDP/M) prolongs survival as compared to streptozotocin and mitotane (Sz/M) in patients with advanced adrenocortical carcinoma (ACC) whose disease is not amenable to complete surgical resection.
NCT00094497 ↗	Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)	Completed	National Cancer Institute (NCI)	Phase 3	2004-06-01	The purpose of this study is to determine whether treatment with etoposide, doxorubicin, cisplatin and mitotane (EDP/M) prolongs survival as compared to streptozotocin and mitotane (Sz/M) in patients with advanced adrenocortical carcinoma (ACC) whose disease is not amenable to complete surgical resection.
NCT00094497 ↗	Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)	Completed	Collaborative Group for Adrenocortical Carcinoma Treatment	Phase 3	2004-06-01	The purpose of this study is to determine whether treatment with etoposide, doxorubicin, cisplatin and mitotane (EDP/M) prolongs survival as compared to streptozotocin and mitotane (Sz/M) in patients with advanced adrenocortical carcinoma (ACC) whose disease is not amenable to complete surgical resection.

Clinical Trial Conditions for mitotane

Condition Name

Condition Name for mitotane
Intervention	Trials
Adrenocortical Carcinoma	11
Adrenal Cortex Neoplasms	2
Stage III Adrenocortical Carcinoma	2
Stage IV Adrenocortical Carcinoma	2

Condition MeSH

Condition MeSH for mitotane
Intervention	Trials
Adrenocortical Carcinoma	19
Carcinoma	17
Adrenal Cortex Neoplasms	4
Syndrome	2

Clinical Trial Locations for mitotane

Trials by Country

Trials by Country for mitotane
Location	Trials
United States	84
Canada	7
Italy	6
Germany	3
Netherlands	3

Trials by US State

Trials by US State for mitotane
Location	Trials
Maryland	7
Michigan	6
Texas	5
Illinois	3
California	3

Clinical Trial Progress for mitotane

Clinical Trial Phase

Clinical Trial Phase for mitotane
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	5
Phase 2	16

Clinical Trial Status

Clinical Trial Status for mitotane
Clinical Trial Phase	Trials
Completed	8
Recruiting	6
Unknown status	3

Clinical Trial Sponsors for mitotane

Sponsor Name

Sponsor Name for mitotane
Sponsor	Trials
National Cancer Institute (NCI)	9
M.D. Anderson Cancer Center	3
Azienda Ospedaliera Spedali Civili di Brescia	3

Sponsor Type

Sponsor Type for mitotane
Sponsor	Trials
Other	35
NIH	9
Industry	5

Mitotane Market Analysis and Financial Projection

Mitotane: Clinical Trials, Market Analysis, and Projections

Introduction to Mitotane

Mitotane, also known as Lysodren, is a unique chemotherapy agent specifically approved for the treatment of adrenocortical carcinoma (ACC), a rare and aggressive cancer of the adrenal cortex. It works by reducing steroid production in the adrenal cortex, making it a crucial component in the management of ACC.

Current Clinical Trials and Efficacy

Adjuvant Therapy in ACC

One of the significant ongoing clinical trials is the ADIUVO-2 study, coordinated by the MD Anderson Center in Houston. This prospective, randomized, open-label, stratified, multi-center phase III trial aims to compare the efficacy of a combination of cisplatin plus etoposide (with or without mitotane) against the current best practice of mitotane or no therapy in patients with ACC after primary surgical resection. The study focuses on high-risk patients with a Ki67 expression of 10% or higher, where the risk of recurrence is high[1].

Mitotane vs. Other Therapies

Previous studies have shown that mitotane alone can improve relapse-free survival (RFS) and overall survival (OS) in ACC patients, particularly in those with low to intermediate risk. However, its efficacy in highly proliferating ACC is limited due to the time required to achieve therapeutic serum levels, which can take 2-3 months. During this period, disease recurrence may occur. The FIRM-ACT study, the only phase III trial conducted to date, found that mitotane combined with cisplatin-based chemotherapy was superior to mitotane combined with streptozocin in terms of progression-free survival and overall survival in advanced/metastatic ACC patients[1].

Ongoing Evaluations

The ADIUVO-2 study is critical because there are no ongoing studies testing adjuvant therapies in radically operated ACC patients with a high risk of relapse and death. The trial will evaluate the recurrence of ACC using imaging techniques every 4 months for the first 2 years and then every 6 months until the 4th year[1].

Market Analysis and Projections

Global Market Outlook

The mitotane market is expected to grow significantly over the next decade. As of 2024, the global market value is estimated to be $17.6 million and is projected to increase to $29.9 million by 2034, with a compound annual growth rate (CAGR) of 5.4%[2].

Key Market Drivers

• Increasing Awareness and Prevalence of Adrenal Gland Cancer: Growing awareness of cancer and its treatments is driving demand for mitotane. The drug's efficacy in treating ACC and its role in postoperative adjuvant therapy contribute to its market growth[2][3].
• Regulatory Environment: The orphan drug status of mitotane, particularly in countries like China, extends market exclusivity and reduces the risk of generic competition, fostering a favorable regulatory environment for pharmaceutical investments[2].
• Clinical Trials and Research: The increasing number of randomized trials evaluating the potential of mitotane in adjuvant therapy is expected to boost the market. Recent studies exploring its use in patients after complete surgical resection and its potential in treating Cushing’s disease are also driving growth[3].

Regional Market Dynamics

• North America and Europe: These regions are expected to remain highly lucrative due to the expanding array of clinical studies and the favorable regulatory landscape. North America's market value is projected to grow from $5.6 million in 2024 to $9.32 million by 2034, with a CAGR of 5.2%[2].
• Asia Pacific: The growing incidence of ACC in this region is expected to expand the global market potential. China, in particular, is seeing significant growth due to the orphan drug status of mitotane, which encourages pharmaceutical investments and ensures a steady supply of the drug[2][3].

Market Restraints

• Limited Patient Base: The rarity of ACC limits the patient population requiring mitotane, making it a specialized market. This constraint affects the scale of clinical trials and pharmaceutical investments[2].
• Side Effects and Alternative Therapies: While mitotane is effective, it has notable side effects, and the emergence of alternative therapies could impact its market share. However, the current lack of alternative options maintains its market position[2][3].

Distribution and Sales Channels

The mitotane market is primarily driven through specialty clinics, which are expected to expand at a CAGR of 4.8% from 2024 to 2034. This segment is crucial due to the specialized nature of the treatment and the need for close monitoring and care[2].

Key Players and Market Competition

Several pharmaceutical companies are key players in the mitotane market, including HRA Pharma Rare Diseases, Bristol-Myers Squibb Company, TherDose Pharma Pvt. Ltd., Hikma Pharmaceuticals, and Novartis Pharmaceuticals Corporation. These companies are investing in the development, manufacturing, and marketing of mitotane, ensuring its availability and affordability for patients[2].

Future Prospects and Potential Applications

Broadening Indications

Mitotane's potential applications may extend beyond ACC through further research and clinical trials. It holds promise in treating other rare cancers and conditions, which could broaden its market penetration and revenue prospects. The orphan drug status in countries like China provides a favorable environment for exploring these new indications[2][3].

Clinical Trial Outcomes

Studies like the one analyzing the outcomes of patients included in early clinical trials suggest that participation in these trials can significantly improve progression-free survival and overall survival for patients with metastatic ACC. Such outcomes highlight the importance of continued clinical research in optimizing mitotane therapy[4].

"Mitotane's orphan drug status presents a unique opportunity for pharmaceutical companies in China. This designation prolongs market exclusivity for mitotane, mitigating the risk of generic competition and fostering a favorable regulatory environment"[2].

Key Takeaways

• Clinical Trials: Ongoing trials like ADIUVO-2 are crucial for evaluating the efficacy of mitotane in combination with other chemotherapies in high-risk ACC patients.
• Market Growth: The mitotane market is expected to grow at a CAGR of 5.4% from 2024 to 2034, driven by increasing awareness, favorable regulatory environments, and ongoing clinical research.
• Regional Dynamics: North America and Europe are key markets, while the Asia Pacific region is expected to grow due to increasing incidence of ACC.
• Market Restraints: The limited patient base and potential side effects are significant restraints, but the current lack of alternative therapies maintains mitotane's market position.
• Future Prospects: Mitotane's potential applications may extend beyond ACC, and its orphan drug status in countries like China provides a favorable environment for further research.

FAQs

What is the primary use of mitotane in medical treatment?

Mitotane is primarily used for the treatment of adrenocortical carcinoma (ACC), a rare and aggressive cancer of the adrenal cortex. It is also used as an adjuvant therapy after surgical resection and in the management of Cushing’s disease.

What are the key drivers of the mitotane market?

The key drivers include increasing awareness and prevalence of adrenal gland cancer, favorable regulatory environments, and ongoing clinical trials evaluating its efficacy in adjuvant therapy.

What are the projected market values for mitotane from 2024 to 2034?

The global mitotane market is expected to grow from $17.6 million in 2024 to $29.9 million by 2034, with a CAGR of 5.4%.

Which regions are expected to be lucrative markets for mitotane?

North America and Europe are expected to remain highly lucrative due to the expanding array of clinical studies and favorable regulatory landscapes. The Asia Pacific region, particularly China, is also expected to grow due to the increasing incidence of ACC.

What are the potential future applications of mitotane beyond ACC?

Mitotane may have potential applications in treating other rare cancers and conditions, extending its market penetration and revenue prospects under the orphan drug framework.

How does the orphan drug status of mitotane impact its market?

The orphan drug status of mitotane extends market exclusivity, reduces the risk of generic competition, and fosters a favorable regulatory environment for pharmaceutical investments, particularly in countries like China.

Sources

1. CenterWatch: "Adjuvant Chemotherapy vs. Observation/Mitotane After Primary Surgical Resection of Localized Adrenocortical Carcinoma"[1].
2. Fact.MR: "Mitotane Market Share and Growth Analysis - 2034"[2].
3. BioSpace: "Mitotane Market Segmentation and Forecast Analysis up to 2027"[3].
4. PubMed: "Outcome of adrenocortical carcinoma patients included in early clinical trials in second line"[4].
5. ASD Reports: "Mitotane Market Study by Cushing's Disease (CD) and Adrenocortical Carcinoma (ACC) through Hospital"[5].