To find out if combining psychoeducational interventions (such as education, counseling, and self-managed therapies) with an open-label placebo can help to improve your quality of life better than either the psychoeducational interventions or the placebo alone.

Primary Objectives:

1. To determine if the combination therapy of PI with OLP (combination therapy group) is superior to PI alone group in the treatment of cancer-related fatigue (CRF) as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale.

We hypothesize that the combination of OLP+PI in these patients will result in a greater reduction of CRF compared to PI alone.

Secondary Objectives:

1. To determine if Combination Therapy group is superior to PI Only group for the treatment of CRF at 3 months and 6 months after treatment. We hypothesize that the combination of OLP+PI in these patients will result in a greater reduction of CRF after 3 months and 6 months after treatment

3. To determine the effects of combination therapy on fatigue-related quality-of-life, mood, sleep-wake activity, cognitive measures, and inflammation. We will assess measures including quality of life (Functional Assessment of Cancer Therapy - General, FACT- G), multidimensional fatigue (Multidimensional Fatigue Symptom Inventory, MFSI-SF), sleep disturbance (PROMIS-sleep), anxiety (Hospital Anxiety and Depression Scale - HADS), depressed mood (HADS), cognitive function (Symbol digit modality test, SDMT), sleep/wake time activity (actigraphy), and inflammation (C-reactive protein levels).

We hypothesize that combination therapy will result in improvements in CRF-related quality of life, mood, sleep-wake activity, and cognitive measures.

Inclusion Criteria:

1. Be advanced cancer patients or s or have a history of advanced cancer, having fatigue with severity of ≥ 4/10, on a 0-10 scale (Edmonton Symptom Assessment Scale), and presence of fatigue for at least 2 weeks.
2. Have no clinical evidence of cognitive failure as evidenced by treating clinician assessment at screening (Memorial Delirium Assessment Scale of less than 13/30).
3. Be aged 18 years or older.
4. Be willing to complete in-person or with research staff, and able to complete Psychoeducational intervention either in person or virtually within Texas.
5. Have a hemoglobin level of ≥10 g/dL within 2 weeks of enrollment.
6. Be able to understand the description of the study and sign a written informed consent.
7. Have a ECOG performance status score of 0 to 2; and
8. Be seen at an outpatient clinic at MD Anderson Cancer Center's (MDA) main campus or its Houston Area Locations (HALs)
9. Able to read, write and speak English

Exclusion Criteria:

1. Have a major contraindication to placebo (e.g., allergy or hypersensitivity to study medications or their constituents), or conditions making adherence difficult as determined by the attending physician.
2. Be unable to complete the baseline assessment forms or to understand the recommendations for participation in the study.
3. Be pregnant (as documented in chart) or become pregnant while on study.