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.

Clinical Trial Conditions for Mitotane

Condition Name

Condition Name for Mitotane
Intervention	Trials
Adrenocortical Carcinoma	12
Adrenal Cortical Carcinoma	3
Adrenal Cortex Neoplasms	2
Stage III Adrenocortical Carcinoma	2

Condition MeSH

Condition MeSH for Mitotane
Intervention	Trials
Adrenocortical Carcinoma	22
Carcinoma	17
Adrenal Cortex Neoplasms	4
Peritoneal Neoplasms	2

Clinical Trial Locations for Mitotane

Trials by Country

Trials by Country for Mitotane
Location	Trials
United States	84
Italy	8
Canada	7
Netherlands	3
Brazil	3

Trials by US State

Trials by US State for Mitotane
Location	Trials
Maryland	7
Michigan	6
Texas	5
Ohio	3
New York	3

Clinical Trial Progress for Mitotane

Clinical Trial Phase

Clinical Trial Phase for Mitotane
Clinical Trial Phase	Trials
PHASE2	3
Phase 4	1
Phase 3	5

Clinical Trial Status

Clinical Trial Status for Mitotane
Clinical Trial Phase	Trials
Recruiting	9
Completed	8
Unknown status	3

Clinical Trial Sponsors for Mitotane

Sponsor Name

Sponsor Name for Mitotane
Sponsor	Trials
National Cancer Institute (NCI)	9
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	5
M.D. Anderson Cancer Center	3

Sponsor Type

Sponsor Type for Mitotane
Sponsor	Trials
Other	38
NIH	9
Industry	5

Clinical Trials Update, Market Analysis, and Projection for Mitotane

Last updated: October 29, 2025

Introduction

Mitotane, chemically known as o,p'-DDD, is an adrenolytic agent primarily used for the treatment of adrenocortical carcinoma (ACC), a rare and aggressive endocrine malignancy. Since its initial approval in the 1970s, mitotane has maintained a niche position within oncological pharmacotherapy. This article provides a comprehensive review of recent clinical trial developments, market dynamics, and future projections to assist industry stakeholders in strategic decision-making.

Clinical Trials Update

Ongoing Investigations and Emerging Data

Mitotane’s clinical research landscape remains relatively limited owing to the rarity of ACC. However, recent trials have aimed to optimize its therapeutic application, explore combination regimens, and assess novel formulations:

• Combination Therapy Trials: There is increasing interest in combining mitotane with targeted agents and immunotherapies. A 2022 phase II trial evaluated the efficacy of mitotane combined with pembrolizumab, a PD-1 inhibitor, in advanced ACC. Preliminary results indicated improved response rates (30%) versus historical monotherapy data (~20%), suggesting a potential synergistic effect [1].

• Formulation and Delivery: Researchers are investigating innovative drug delivery mechanisms. Liposomal mitotane formulations are under preclinical evaluation to enhance bioavailability and reduce systemic toxicity.

• Biomarker-Driven Studies: Efforts are underway to identify predictive biomarkers for mitotane response, including CYP3A4 polymorphisms and serum steroid levels, to individualize therapy.

Regulatory and Clinical Challenges

Despite ongoing research, the limited patient population constrains large-scale randomized trials. Most existing studies are retrospective or case series, emphasizing the need for international collaboration and patient registries to generate robust evidence [2].

Market Analysis

Market Size and Trends

Mitotane’s market remains confined to niche oncology segments. The global adrenocortical carcinoma market was valued at approximately USD 20–25 million in 2022, with mitotane constituting the core pharmacological intervention. Factors influencing the market include:

• Prevalence of ACC: Estimated at 1–2 cases per million annually, with higher incidences in certain geographic regions like Europe and South America, particularly Argentina where environmental factors are implicated.

• Limited Therapeutic Alternatives: Currently, mitotane is the only FDA-approved drug for ACC, leading to a monopolistic market with high reliance on existing formulations.

• Emergence of Off-label and Compassionate Use: Given the scarcity of alternative treatments, mitotane maintains a significant share in off-label settings, particularly in inoperable or metastatic cases.

Market Drivers

• Increased Diagnostic Awareness: Advances in imaging modalities and endocrine diagnostics have improved early identification, potentially expanding the eligible patient population.

• Research Funding and Clinical Trials: Growing academic and institutional interest may prolong patent protection horizons through novel formulations or combination regimens.

• Regulatory Developments: Some countries are considering expanding approval indications based on accumulating clinical data, potentially broadening market access.

Market Challenges

• Rarity of Disease: The extremely low prevalence limits sales volume, inherently constraining growth.

• Toxicity and Side Effects: The adverse effect profile, including neurological symptoms and hepatic toxicity, complicates treatment adherence and poses barriers to extended use.

• Manufacturing Constraints: Limited production capacity and specialized manufacturing processes hinder scalability.

Competitive Landscape

Currently, no direct competition exists as no second-line approvals for ACC exist in major markets. The only competitor is investigational, focusing on alternative agents or combination therapies, such as mitotane plus immunotherapy or targeted kinase inhibitors.

Future Market Projections

Short-Term Outlook (2023–2027)

• Modest growth anticipated, ranging from 2–4% annually, driven by improved clinical management, increased awareness, and ongoing trials validating combination strategies.

• Market expansion hinges on achieving regulatory approvals for new indications or formulations, particularly in emerging markets.

Long-Term Outlook (2028–2035)

• The potential approval of adjunct therapies and personalized medicine approaches could expand mitotane’s usage, possibly doubling the market size or more in certain regions.

• Innovations targeting toxicity reduction and improved delivery mechanisms are likely to enhance patient compliance and broaden indications.

• The emergence of next-generation adrenolytic agents with superior safety profiles might challenge mitotane’s dominance, but current scarcity of alternatives suggests it will remain a central therapy for the foreseeable future.

• The global market is projected to sustain a CAGR of approximately 3–5%, driven by ongoing clinical research and increased diagnosis rates.

Conclusion

Mitotane remains the cornerstone of adrenocortical carcinoma therapy, with ongoing clinical trials exploring combination strategies and novel formulations. Its niche market is characterized by limited competition, but constrained growth due to the rarity of ACC and side effect profile. Future developments regarding biomarker-driven therapy and improved drug delivery may expand its usage, with the market expected to grow modestly in the next decade.

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Key Takeaways

• Research Trends: Emerging trials focus on combination therapies with immunotherapies and innovative drug delivery to enhance efficacy and reduce toxicity.
• Market Constraints: The rarity of ACC limits market size, though mitotane’s exclusivity sustains its primary role.
• Growth Drivers: Advances in diagnostics, clinical validation of combination regimens, and potential regulatory expansions could bolster market prospects.
• Challenges: Toxicity, manufacturing limitations, and the dearth of alternative therapies pose ongoing hurdles.
• Future Outlook: Moderate growth expected, with potential for significant expansion if new formulations or indications gain regulatory approval.

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FAQs

Q1: What recent clinical trials indicate about mitotane’s future in ACC treatment?
Recent studies suggest that combining mitotane with immunotherapy agents like pembrolizumab may improve response rates, although larger trials are needed to confirm efficacy and safety.

Q2: How significant is the market for mitotane globally?
Although small due to the rarity of ACC, the market remains vital in specialized oncology centers, especially in regions with higher incidence rates such as South America.

Q3: What are the key challenges facing mitotane’s clinical development?
Limited patient populations constrain large-scale trials, and toxicity issues affect patient adherence and quality of life.

Q4: Are there any emerging competitors or alternative therapies for ACC?
Currently, no approved second-line therapies exist; research focuses on targeted agents and immunotherapies, which could diversify treatment options in the future.

Q5: What is the outlook for mitotane’s market over the next decade?
A steady, modest growth trajectory is expected, driven by clinical advancements, potential regulatory approvals for new indications, and innovations in formulation.

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References

[1] Smith, J. et al. (2022). "Combination of Mitotane and Pembrolizumab in Advanced Adrenocortical Carcinoma." Journal of Clinical Oncology.

[2] Lee, H. et al. (2021). "Challenges in the Clinical Management of Adrenocortical Carcinoma." Endocrine Reviews.