Symptom Research Clinical Trials

2006-0022: A Phase II study of Minocycline vs. Placebo to Prevent Treatment-Induced Neuropathy in Multiple Myeloma

Principal Investigator: Sheeba Thomas; Grant PI: Charles Cleeland  ● Funding: NIH P01 CA124787

Clinicaltrials.gov # NCT01283997

Nearly all patients with multiple myeloma eventually require single or combination therapy with thalidomide and/or bortezomib. These agents are known to cause neuropathy in a significant percentage of patients. The incidence of neuropathy is much higher in relapsing patients and increases further in the presence of diabetes or amyloidosis. Preexisting neuropathy is a risk factor for higher rates and increased severity of treatment-related neuropathy in these patients. In some patients, the neuropathy induced by these drugs can be so severe that it affects treatment compliance and can even result in discontinuation of otherwise effective antineoplastic therapy. 

Inhibition of proinflammatory cytokines may prevent or reduce the degree of neuropathy induced by these agents. The primary objective of this clinical trial is to explore proinflammatory cytokine blockade for preventing or ameliorating neuropathy induced by thalidomide and/or bortezomib in previously untreated patients with myeloma.  

Primary Objectives: (1) To compare the safety of minocycline vs. placebo in patients receiving induction therapy for multiple myeloma with a regimen containing thalidomide and/or bortezomib. (2) To compare the effect of minocycline vs. placebo on peripheral nerve function in these patients.

Secondary Objectives: (1) To evaluate the effect of minocycline vs. placebo on neuropathic symptoms in these patients. (2) To evaluate the effect of minocycline vs. placebo on serum cytokine levels. (3) To evaluate the effect of  minocycline vs. placebo on neurocognitive function. (4) To evaluate the effect of minocycline vs. placebo on daytime somnolence.

This study is ongoing but is not recruiting participants.

2010-0096: Minocycline for Reduction of Radiation Therapy Treatment-Related Symptom Burden in Head and Neck Cancer: A Randomized Study

Clinicaltrials.gov # NCT01173692

Principal Investigator: Brandon Gunn; Grant PI: Charles Cleeland  ● Funding: NIH R01 CA026582

The study aims to test a symptom-reduction strategy based on underlying symptom mechanisms associated with cancer treatments. Using a blinded, randomized placebo-controlled trial, we will evaluate the ability of minocycline, a widely used, low-toxicity, low-cost symptom therapy, to reduce the symptom burden of oropharyngeal cancer, nasopharyngeal cancer, or unknown primary cancer of head and neck treated with radiation therapy. Minocycline is known to have anti-inflammation properties and is able to cross the blood–brain barrier, possibly reducing inflammation in the central nervous system and the expression of multiple symptoms at the brain level. If successful, this research could establish a simple symptom-prevention therapy for a disease and treatment for which the symptom burden is high and few medical symptom prevention strategies exist.

Primary Objective: To test the efficacy of minocycline in reducing multiple patient-reported symptoms in patients with oropharyngeal cancer, nasopharyngeal cancer, or unknown primary cancer of the head and neck treated with definitive radiation therapy.

This study is ongoing but is not recruiting participants.

2010-0557: Armodafinil for Persistent Patient-Reported Fatigue Following Radiation Therapy for Head and Neck Cancer: A Randomized Phase II Study

Clinicaltrials.gov # NCT01330446

Principal Investigator: Brandon Gunn; Grant PI: Charles Cleeland  ● Funding: NIH R01 CA026582

Fatigue is one of the most severe symptoms reported by patients with head and neck cancer at any time point during or after radiotherapy or chemoradiation. Fatigue that persists months after the end of treatment can interfere with returning to work or with functional recovery. In this study, we evaluate the ability of armodafinil, a wakefulness-promoting agent, to reduce patient-reported fatigue after therapy has been completed. The target of action is armodafinil’s alertness-promoting property, which could impact patient-reported fatigue, other associated symptoms, and symptom interference with daily activities. If successful, this research could establish a simple symptom-intervention therapy for fatigue, for which few proven medical symptom intervention strategies exist.

Primary Objective: To evaluate the ability of armodafinil to reduce patient-reported fatigue in patients with treated head and neck cancer.

Secondary Objective: To explore the effect of armodafinil in reducing symptom severity and symptom interference, enhancing patient-reported alertness, and improving work productivity and activity.

This study is ongoing but is not recruiting participants.

2012-0347: A Randomized, Placebo Controlled-Double Blind Study of Minocycline for Reducing the Symptom Burden Produced by Chemoradiation Treatment for Non Small Cell Lung Cancer

Principal Investigator: Zhongxing Liao; Grant PI: Charles Cleeland  ● Funding: NIH R01 CA026582

Clinicaltrials.gov # NCT01636934

Patients with non-small cell lung cancer (NSCLC) receiving concurrent chemoradiation therapy (CXRT) report debilitating fatigue and other symptoms during treatment and for several weeks afterward. Treatment tolerability and patient functioning are often compromised by this symptom burden. Few agents have been approved to prevent or treat these side effects, and little is understood about the mechanisms that cause them. However, promising initial clinical studies support the involvement of acute-phase and survival-phase inflammatory responses in producing treatment-related symptom burden. Preclinical and clinical work has evidenced the strong anti-inflammatory properties and neuroprotective function of minocycline, a low-toxicity, low-cost, widely used antibiotic, whose ability to cross the blood–brain barrier and good safety profile make it desirable for directly testing the role of inflammation in producing symptom burden.

Primary Objective: To test the potential utility of minocycline treatments for symptoms that have been identified as prominent during CXRT for NSCLC, including fatigue, pain, disturbed sleep, lack of appetite, and sore throat.

Secondary Objectives: (1) To examine the effectiveness of minocycline in reducing treatment-induced inflammatory response. (2) To examine the impact of minocycline on patient's quality of life, health status, and tumor response to CXRT.

This study is ongoing but is not recruiting participants.

2012-0413: A Phase II Randomized Study of the Efficacy of Minocycline vs. Placebo to Reduce Symptom Burden during Maintenance Therapy for Multiple Myeloma

Principal Investigator: Robert Orlowski; Grant PI: Charles Cleeland  ● Funding: NIH P01 CA124787

Clinicaltrials.gov # NCT01793051

Minocycline is an inexpensive, widely used, semisynthetic antibiotic that has strong preclinical and clinical evidence of anti-inflammatory effects. In an induction-phase study of patients with multiple myeloma, we observed significant longitudinal associations between inflammatory cytokines and symptoms: soluble IL-6 receptor (sIL-6R) was associated with disturbed sleep, poor appetite, and sore mouth; IL-6 was significantly associated with pain, fatigue, nausea, and sore mouth, and monocyte chemotactic protein-1 was positively associated with numbness/tingling. In this trial we are exploring broad proinflammatory cytokine blockade by minocycline, as a rationale for managing the general symptoms of multiple myeloma (fatigue, muscle weakness, and bone aches) and treatment-induced neuropathy (pain and numbness/tingling).

Primary Objective: To test the potential utility of minocycline treatments for ameliorating symptoms that have been identified as prominent during maintenance therapy for multiple myeloma.

Secondary Objectives: (1) To evaluate the effect of minocycline vs. placebo on serum and cell inflammatory markers in this patient cohort. (2) To examine the association between inflammatory markers and symptom expression.

This study is ongoing but is not recruiting participants.

2012-0587: A Randomized, Placebo Controlled-double Blind Study of Minocycline for Reducing the Symptom Burden for Pancreatic Cancer Patients

Principal Investigator: David Fogelman; Grant PI: Xin Shelley Wang  ● Funding: NIH R21 CA158902

Clinicaltrials.gov # NCT01693523

Typically diagnosed with advanced disease, patients with pancreatic cancer suffer from high symptom burden during their limited survival period. Their most disturbing symptoms—often fatigue, poor appetite, drowsiness, disturbed sleep, pain, and distress—present a serious challenge for patient care. We theorize that many of the symptoms of cancer and its treatment are related to cytokine dysregulation. Although inflammatory mechanisms have been investigated with clinical outcomes in pancreatic cancer, to our knowledge no study has examined whether downregulating a network of cytokines would be helpful for symptom reduction, especially for the most severe symptom, fatigue. The common antibiotic minocycline has a wide range of anti-inflammatory effects in the brain and peripheral system and has been used widely as an anti-inflammatory agent in other chronic conditions, but it has never been tested for improving symptoms in pancreatic cancer.

Primary Objective: To establish the efficacy of minocycline in reducing symptoms during a cycle (14 days) of FOLFIRINOX or gemcitabine-based chemotherapy in patients with pancreatic cancer. (References to FOLFIRINOX in this protocol include modified versions of the treatment, such as FOLFOX. Treating oncologists may alter the FOLFIRINOX combination depending on the patient’s condition. )

Secondary Objectives: (1) To establish the efficacy of minocycline in reducing symptoms beyond the first cycle of FOLFIRINOX or gemcitabine-based chemotherapy in patients with pancreatic cancer. (2) To characterize the effect of minocycline on modulating inflammatory biomarkers and their possible association with dynamic changes in symptom burden. (3) To examine the potential effects of minocycline on preventing rapid increase of cytokine release in patients with mild baseline symptoms. (4) To examine the effect of minocycline on muscle and fat mass and wasting. (5) To examine the effect of minocycline on managing disease-driven symptoms for 2 weeks before the start of chemotherapy. (6) To characterize the effect of FOLFIRINOX and disease progression on the development of high symptom burden.

This study is ongoing but is not recruiting participants.

2013-0323: Phase II, Randomized, Placebo-Controlled Study of Minocycline for Reducing Symptom Burden in Patients with Colorectal Cancer

Principal Investigator: Cathy Eng; Grant PI: Xin Shelley Wang  ● Funding: American Cancer Society 

Clinicaltrials.gov # NCT01906008

Oxaliplatin, a standard chemotherapeutic agent for colorectal cancer, confers significant clinical benefit but also causes acute and chronic neurotoxicity. As a dose-limiting toxic effect, oxaliplatin-induced peripheral neuropathy interferes with functional ability, causes distress, and persists into survivorship for thousands of patients; it also can compromise adherence to therapy. Nearly 40% of patients with CRC receiving oxaliplatin-based chemotherapy experience neuropathy that is significant enough to cause dose reduction or withdrawal. Preclinical animal modeling has provided strong evidence that the common antibiotic minocycline has a neuroprotective effect on oxaliplatin-induced hyperalgesia.

Primary Objective: To examine the clinical efficacy of minocycline in reducing acute peripheral neuropathy during oxaliplatin-based chemotherapy in patients with colorectal cancer (CRC).

Secondary Objectives: (1) To examine the clinical efficacy of minocycline in reducing fatigue during oxaliplatin-based chemotherapy in patients with CRC. (2) To examine the impact of socioeconomic status (SES) on the clinical efficacy of minocycline in reducing acute peripheral neuropathy during oxaliplatin-based chemotherapy in patients with CRC. (3) To examine the interaction between SES and inflammation (circulating cytokines and activation of immune cells) and the effect of these variables on symptom severity in CRC patients. (4) To explore the relationship between objective measures of neuropathy and  patient-reported symptom outcome measures and health status.

This study is ongoing but is not recruiting participants.

2013-0510: Minocycline for Reduction of Symptom Burden after Surgery in Patients With Head and Neck Malignancy: A Randomized Study

Principal Investigator: Juan Cata; Grant PI: Charles Cleeland  ● Funding: NIH R01 CA026582

Clinicaltrials.gov # NCT02055963

The primary treatment for most patients with head and neck cancer is tumor-reductive surgery followed by chemoradiotherapy. The insult of tumor-reductive surgery produces an inflammatory reaction that is a classic feature of surgical trauma and that could constitute the mechanism behind increases in postsurgical symptoms, such as pain, sleep disturbance, dry mouth, difficulty swallowing, and fatigue. The study aims to test a symptom-reduction strategy based on minocycline, a common antibiotic with anti-inflammatory properties, to address the underlying symptom mechanisms associated with cancer treatments, so as to improve patient outcomes.

Primary Objective: To test the efficacy of minocycline in reducing multiple patient-reported symptoms in patients who are undergoing surgery for head and neck cancer.

Secondary Objectives: (1) To explore predictors of symptom recovery and whether these predictors are influenced by a minocycline intervention. (2) To examine whether the longitudinal pattern of local (saliva) and systemic (plasma) release of damage-associated molecular patterns and subsequent inflammatory responses during cancer treatment may represent biomarkers of the underlying mechanism of symptom burden.

This study is ongoing but is not recruiting participants.

2014-0233: Mindfulness-Based Couples Therapy for Breast Cancer Survivors: A Pilot Study

Principal Investigator:  Cobi Heijnen  ● Funding: PI Startup Funds

Clinicaltrials.gov # NCT02349217

Inflammation is now regarded as a risk factor for most cancers, based on evidence that it influences tumor promotion, survival, proliferation, invasion, angiogenesis, and metastasis and that it appears to be a major factor affecting post-treatment quality of life. Depression and psychosocial stress can directly promote proinflammatory cytokine production, and a turbulent couples relationship marked by hostility and conflict is a rich source for both. Mindfulness-Based Relationship Enhancement (MBRE) is a stress-reducing intervention designed to alleviate stress and reduce depressive symptoms among couples, with a particular focus on loving-kindness practices and compassion toward one’s partner. This study explores the feasibility and effectiveness of an MBRE intervention in terms of relationship satisfaction, quality of life, and immune dysregulation among breast cancer survivors and their partners.

Primary Objectives: (1) To determine the feasibility of recruiting and implementing an MRBE intervention among breast cancer survivors and their partners. (2) To pilot test and evaluate the efficacy of a mind–body intervention to enhance relationship satisfaction and promote better quality of life, reduce autonomic and immune dysregulation, and change the gut microbiota.

This study is ongoing but is not recruiting participants.